Research Projects (Third party funds)

MAGICPAH

Molecular Approaches and MetaGenomic Investigations for optimizing Clean-up of PAH contaminated site

MAGICPAH aims to explore, understand and exploit the catalytic activities of microbial communities involved in the degradation of persistent PAHs. It will integrate (meta-) genomic studies with in-situ activity assessment based on stable isotope probing particularly in complex matrices of different terrestrial and marine environments. PAH degradation under various conditions of bioavailability will be assessed as to improve rational exploitation of the catalytic properties of bacteria for the treatment and prevention of PAH pollution. We will generate a knowledge base not only on the microbial catabolome for biodegradation of PAHs in various impacted environmental settings based on genome gazing, retrieval and characterization of specific enzymes but also on systems related bioavailability of contaminant mixtures. MAGICPAH takes into account the tremendous undiscovered metagenomic resources by the direct retrieval from genome/metagenome libraries and consequent characterization of enzymes through activity screens. These screens will include a highend functional small-molecule fluorescence screening platform and will allow us to directly access novel metabolic reactions followed by their rational exploitation for biocatalysis and the re-construction of biodegradation networks. Results from (meta-) genomic approaches will be correlated with microbial in situ activity assessments, specifically dedicated to identifying key players and key reactions involved in anaerobic PAH metabolism. Key processes for PAH metabolism particularly in marine and composting environments and the kinetics of MAGICPAH aims to explore, understand and exploit the catalytic activities of microbial communities involved in the degradation of persistent PAHs. It will integrate (meta-) genomic studies with in-situ activity assessment based on stable isotope probing particularly in complex matrices of different terrestrial and marine environments. PAH degradation under various conditions of bioavailability will be assessed as to improve rational exploitation of the catalytic properties of bacteria for the treatment and prevention of PAH pollution. We will generate a knowledge base not only on the microbial catabolome for biodegradation of PAHs in various impacted environmental settings based on genome gazing, retrieval and characterization of specific enzymes but also on systems related bioavailability of contaminant mixtures. MAGICPAH takes into account the tremendous undiscovered metagenomic resources by the direct retrieval from genome/metagenome libraries and consequent characterization of enzymes through activity screens. These screens will include a high-end functional small-molecule fluorescence screening platform and will allow us to directly access novel metabolic reactions followed by their rational exploitation for biocatalysis and the re-construction of biodegradation networks. Results from (meta-) genomic approaches will be correlated with microbial in situ activity assessments, specifically dedicated to identifying key players and key reactions involved in anaerobic PAH metabolism. Key processes for PAH metabolism particularly in marine and composting environments and the kinetics of aerobic degradation of PAH under different conditions of bioavailability will be assessed in model processes for PAH metabolism particularly in marine and composting environments and the kinetics of aerobic degradation of PAH under different conditions of bioavailability will be assessed in model systems, the rational manipulation of which will allow us to deduce correlations between system performance and genomic blueprint. The results will be used to improve treatment of PAH-contaminated sites.

Partners

 

Consejo Superior de Investigaciones Cientificas (CSIC)

Istituto per l’Ambiente Marino Costiero (IAMC)

Bangor University (UB)

Danmarks Tekniske Universitet (DTU)

Aecom

Genoscope / Institut de Génomique du CEA

Helmholtz Centre for Environmental Research - UFZ

National Environmental Research Institute at the University of Aarhus

Syndial Attività Diversificate SpA

Corporacion Corpogen

University Toronto

University of Leipzig

 

 

Leader

Groups

Speaker

Dietmar Pieper

Coordinator

Helmholtz-Zentrum für Infektionsforschung GmbH

Funding agency

EU-Projects

CAREPNEUMO

Combating Antibiotics Resistant Pneumococci by Novel Strategies Based on in vivo and in vitro Host-Pathogen Interactions

CAREPNEUMO LogoThis collaborative project is aimed at understanding pneumococcus-host interactions for developing novel combat strategies.

The objective is to provide the basic knowledge needed for future development of novel prevention, diagnostic and treatment tools against pneumococcal infections. Emphasis will be placed on studies into fundamental molecular aspects of the interactions between S. pneumoniae and the human host, in particular the cell biology of bacteria. Experimental approaches will include the use of cell cultures and animal models of pneumococcal diseases, the study of virulence mechanisms, as well as the molecular epidemiology of drug resistance. CAREPNEUMO brings together 12 research organizations and one SME to achieve the objectives of the call. 

Carepneumo

is a collaborative research project within the Seventh Framework Programme funded by European Commission

from 01.03. 2009-28.02.2012.

(FP-Health-2007-B)

Contract No. 22311

The need to meet the challenge of Streptococcus pneumoniae

 

Streptococcus pneumoniae is a major cause of life-threatening infections such as pneumonia, meningitis and septicemia. The disease burden is high both in developed and developing countries, and the high-risk groups include children, elderly persons and immuno compromised patients. Approximately one million children under 5 years of age die from pneumococcal infections every year. In spite of the availability of a large number of antibiotics mortality and morbidity due to S. pneumoniae infections remain very high. The worldwide emergence of multi drug resistant S. pneumoniae strains is a big hindrance in treating pneumococcal invasive diseases. 

Another problem in combating pneumococcal infections is the genetic diversity of circulating strains. Based on the capsular polysaccharide there are more than 90 structurally and chemically different serotypes. It is known that different serotypes are prevalent in different geographical regions of the world. Although a 7-valent conjugate vaccine is currently available and has proved to be successful in preventing invasive disease caused by the vaccine serotype strains, the worldwide coverage is limited. Moreover, the use of this vaccine has resulted in a replacement by non-vaccine serotypes, which may make the current vaccine ineffective in the near future. The development of novel combat strategies is urgently needed and is a big challenge for the international pneumococcal community. This is also the global aim of the present proposal. 

There are three prerequisites to achieve this goal. It is important firstly to understand the distribution of serotypes and the occurrence of antibiotic resistance, secondly to identify and characterize new intervention targets by studying host-pathogen interactions, and thirdly to validate these targets in in vitro and in vivo infection models in order to identify potential candidates for prevention and therapy. 

This proposal would apply a multi-disciplinary approach that includes epidemiology, host-pathogen interactions, infection models and intervention strategies to combat antibiotic resistance problems among S. pneumoniae. 

Project Objectives

The objectives of this proposal were defined in order to obtain new knowledge on the molecular epidemiology of pneumococcal diseases and antibiotic resistance in different parts of the world, apply state-of-the-art technology to study host-pathogen interactions and apply innovative technologies for improving existing intervention strategies. Moreover, it would contribute towards the implementation of measures for prevention, control and treatment of pneumococcal diseases, especially those caused by multi-drug resistant strains. To achieve the purpose of this proposal, we have assembled a team with expertise required to fulfil the following objectives:

Objective 1:

Epidemiology of drug resistance and vaccine pressure replacement of S. pneumoniae

The major tasks of this objective will be to undertake monitoring of prevalent S. pneumoniae serotypes and their resistance profiles in various countries. This will also include the epidemiology of the serotype replacement in areas where pneumococcal vaccine is in use. Since the prevalence of serotypes as well as the magnitude and quality of drug resistance is different in different parts of the world, this objective will address the epidemiology of S. pneumoniae in six countries, which include an Asian and a South American country. These studies will determine the frequency of emergence of antibiotical resistance, particularly in those serotypes that have potential to spread rapidly in the community. The second part of this objective will be to determine the changes in pneumococcal disease after introduction of the 7-valent pneumococcal conjugate vaccine in different regions.

Objective 2: 

Analysis of host-pathogen interactions and identification of potential therapeutic targets and vaccine candidates

A prerequisite for developing new control strategies is the detailed understanding of the interaction between pneumococcus and the host cells. The analysis of host-pathogen interaction will include the prevalent virulent strains, which will be continuously identified in the work packages dealing with the epidemiological studies. The molecular mechanisms of host-pathogen interactions will be elucidated by applying genomics and cell biological approaches. Identification and characterization of the factors involved will be an important part of objective 2. The biological functions of these factors will be determined by using pathogenicity tests involving cell cultures as well as animal models of pneumococcal diseases.

Objective 3: 

Development of improved vaccine and intervention strategies

This objective deals with the development of new therapeutic and vaccine tools against pneumococcal infections based on the knowledge generated in objectives 1 and 2. For designing new therapeutics, the molecular basis of pathogen recognition through specific components of pneumococcal cell wall by host proteins will be identified by using a structural biological approach. In the area of vaccine development, this objective will deal with a novel polysaccharide glycolipid conjugate vaccine as well as the development of a protein-based universal vaccine.

Publications

  1. Silva-Martín N, Retamosa MG, Maestro B, Bartual SG, Rodes MJ, García P, Sanz JM, Hermoso JA. (2014) Crystal structures of CbpF complexed with atropine and ipratropium reveal clues for the design of novel antimicrobials against Streptococcus pneumoniae.Biochim Biophys Acta. 1840(1):129-135. doi: 10.1016/j.bbagen.2013.09.006.
  2. Ribes S, Riegelmann J, Redlich S, Maestro B, de Waal B, Meijer EW, Sanz JM, Nau R. (2013) Multivalent Choline Dendrimers Increase Phagocytosis of Streptococcus pneumoniae R6 by Microglial Cells.Chemotherapy. 59(2):138-42. doi: 10.1159/000353439
  3. Chan WT, Moreno-Cordoba I, Yeo CC, Espinosa M (2012) Toxin-antitoxin genes of the Gram-positive pathogen Streptococcus pneumoniae: So few and yet so many.Microbiol Mol Biol Rev 76: 773-791
    2. Moreno-Cordoba I, Diago-Navarro E, Barendregt A, Heck AJ, Alfonso C, Diaz-Orejas R, Nieto C, Espinosa M (2012) The toxin-antitoxin proteins relBE2Spn of Streptococcus pneumoniae: characterization and association to their DNA target.Proteins 80: 1834-1846
  4. Asmat TM, Klingbeil K, Jensch I, Burchhardt G, Hammerschmidt S (2012) Heterologous expression of pneumococcal virulence factor PspC on the surface of Lactococcus lactis confers adhesive properties.Microbiology 158: 771-780 
  5. Djukic M, Munz M, Sorgel F, Holzgrabe U, Eiffert H, Nau R (2012) Overton's rule helps to estimate the penetration of anti-infectives into patients' cerebrospinal fluid.Antimicrobial Agents and Chemotherapy 56: 979-988 
  6. Gamez G, Hammerschmidt S (2012) Combat pneumococcal infections: adhesins as candidates for protein-based vaccine development.Current Drug Targets 13: 323-337 
  7. Haertel T, Eylert E, Schulz C, Petruschka L, Gierok P, Grubmuller S, Lalk M, Eisenreich W, Hammerschmidt S (2012) Characterization of sentral carbon metabolism of Streptococcus pneumoniae by isotopologue profiling. The Journal of Biological Chemistry 287: 4260-4274 
  8. Horacio AN, Diamantino-Miranda J, Aguiar SI, Ramirez M, Melo-Cristino J (2012) Serotype changes in adult invasive pneumococcal infections in Portugal did not reduce the high fraction of potentially vaccine preventable infections.Vaccine 30: 218-224 
  9. Lioy VS, Machon C, Tabone M, Gonzalez-Pastor JE, Daugelavicius R, Ayora S, Alonso JC (2012) The zeta toxin induces a set of protective responses and dormancy.PloS one 7: e30282 
  10. Lorenzo-Diaz F, Solano-Collado V, Lurz R, Bravo A, Espinosa M (2012) Autoregulation of the synthesis of the MobM relaxase encoded by the promiscuous plasmid pMV158.Journal of Bacteriology 194: 1789-1799 
  11. Luettge M, Fulde M, Talay SR, Nerlich A, Rohde M, Preissner KT, Hammerschmidt S, Steinert M, Mitchell TJ, Chhatwal GS, Bergmann S (2012) Streptococcus pneumoniae induces exocytosis of Weibel-Palade bodies in pulmonary endothelial cells.Cellular Microbiology 14: 210-225 
  12. Redlich S, Ribes S, Schutze S, Czesnik D, Nau R (2012) Palmitoylethanolamide stimulates phagocytosis of Escherichia coli K1 and Streptococcus pneumoniae R6 by microglial cells.Journal of Neuroimmunology 244: 32-34 
  13. Ruiz-Maso JA, Lopez-Aguilar C, Nieto C, Sanz M, Buron P, Espinosa M, del Solar G (2012) Construction of a plasmid vector based on the pMV158 replicon for cloning and inducible gene expression in Streptococcus pneumoniae.Plasmid 67: 53-59 
  14. Artola-Recolons C, Llarrull LI, Lastochkin E, Mobashery S, Hermoso JA (2011) Crystallization and preliminary X-ray diffraction analysis of the lytic transglycosylase MltE from Escherichia coli.Acta Crystallographica Section F, Structural Biology and Crystallization Communications 67: 161-163 
  15. Asmat TM, Agarwal V, Rath S, Hildebrandt JP, Hammerschmidt S (2011) Streptococcus pneumoniae infection of host epithelial cells via polymeric immunoglobulin receptor transiently induces calcium release from intracellular stores.The Journal of Biological Chemistry 286: 17861-17869 
  16. Chan WT, Nieto C, Harikrishna JA, Khoo SK, Othman RY, Espinosa M, Yeo CC (2011) Genetic regulation of the yefM-yoeB toxin-antitoxin locus of Streptococcus pneumoniae.Journal of Bacteriology 193: 4612-4625 
  17. Garcia MT, Blazquez MA, Ferrandiz MJ, Sanz MJ, Silva-Martin N, Hermoso JA, de la Campa AG (2011) New alkaloid antibiotics that target the DNA topoisomerase I of Streptococcuspneumoniae.The Journal of Biological Chemistry 286: 6402-6413 
  18. Haertel T, Klein M, Koedel U, Rohde M, Petruschka L, Hammerschmidt S (2011) Impact of glutamine transporters on pneumococcal fitness under infection-related conditions.Infection and Immunity 79: 44-58 
  19. Hernandez-Rocamora VM, Reulen SW, de Waal B, Meijer EW, Sanz JM, Merkx M (2011) Choline dendrimers as generic scaffolds for the non-covalent synthesis of multivalent protein assemblies. Chem Commun (Camb) 47: 5997-5999 
  20. Kreikemeyer B, Gamez G, Margarit I, Giard JC, Hammerschmidt S, Hartke A, Podbielski A (2011) Genomic organization, structure, regulation and pathogenic role of pilus constituents in major pathogenic Streptococci and Enterococci. International Journal of Medical Microbiology (IJMM) 301: 240-251 
  21. Lorenzo-Diaz F, Dostal L, Coll M, Schildbach JF, Menendez M, Espinosa M (2011) The MobM relaxase domain of plasmid pMV158: thermal stability and activity upon Mn2+ and specific DNA binding. Nucleic Acids Research 39: 4315-4329 
  22. Maestro B, Novakova L, Hesek D, Lee M, Leyva E, Mobashery S, Sanz JM, Branny P (2011) Recognition of peptidoglycan and beta-lactam antibiotics by the extracellular domain of the Ser/Thr protein kinase StkP from Streptococcus pneumoniae.FEBS Letters 585: 357-363 
  23. Maestro B, Santiveri CM, Jimenez MA, Sanz JM (2011) Structural autonomy of a beta-hairpin peptide derived from the pneumococcal choline-binding protein LytA.Protein Engineering, Design & Selection (PEDS) 24: 113-122 
  24. Skoczynska A, Sadowy E, Bojarska K, Strzelecki J, Kuch A, Golebiewska A, Wasko I, Forys M, van der Linden M, Hryniewicz W (2011) The current status of invasive pneumococcal disease in Poland.Vaccine 29: 2199-2205 
  25. Agarwal V, Asmat TM, Dierdorf NI, Hauck CR, Hammerschmidt S (2010) Polymeric immunoglobulin receptor-mediated invasion of Streptococcus pneumoniae into host cells requires a coordinate signaling of SRC family of protein-tyrosine kinases, ERK, and c-Jun N-terminal kinase. The Journal of Biological Chemistry 285: 35615-35623 
  26. Aguiar SI, Brito MJ, Goncalo-Marques J, Melo-Cristino J, Ramirez M (2010) Serotypes 1, 7F and 19A became the leading causes of pediatric invasive pneumococcal infections in Portugal after 7 years of heptavalent conjugate vaccine use.Vaccine 28: 5167-5173 
  27. Eldholm V, Johnsborg O, Straume D, Ohnstad HS, Berg KH, Hermoso JA, Havarstein LS (2010) Pneumococcal CbpD is a murein hydrolase that requires a dual cell envelope binding specificity to kill target cells during fratricide.Molecular Microbiology 76: 905-917 
  28. Jensch I, Gamez G, Rothe M, Ebert S, Fulde M, Somplatzki D, Bergmann S, Petruschka L, Rohde M, Nau R, Hammerschmidt S (2010) PavB is a surface-exposed adhesin of Streptococcus pneumoniae contributing to nasopharyngeal colonization and airways infections.Molecular Microbiology 77: 22-43 
  29. Kaur SJ, Nerlich A, Bergmann S, Rohde M, Fulde M, Zahner D, Hanski E, Zinkernagel A, Nizet V, Chhatwal GS, Talay SR (2010) The CXC chemokine-degrading protease SpyCep of Streptococcus pyogenes promotes its uptake into endothelial cells.The Journal of Biological Chemistry 285: 27798-27805 
  30. Kuch A, Sadowy E, Skoczynska A, Hryniewicz W (2010) First report of Streptococcus pneumoniae serotype 6D isolates from invasive infections.Vaccine 28: 6406-6407 
  31. Lioy VS, Pratto F, de la Hoz AB, Ayora S, Alonso JC (2010) Plasmid pSM19035, a model to study stable maintenance in Firmicutes.Plasmid 64: 1-17 
  32. Lioy VS, Rey O, Balsa D, Pellicer T, Alonso JC (2010) A toxin-antitoxin module as a target for antimicrobial development.Plasmid 63: 31-39 
  33. Nau R, Sorgel F, Eiffert H (2010) Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections.Clinical Microbiology Reviews 23: 858-883 
  34. Nieto C, Sadowy E, de la Campa AG, Hryniewicz W, Espinosa M (2010) The relBE2Spn toxin-antitoxin system of Streptococcus pneumoniae: role in antibiotic tolerance and functional conservation in clinical isolates.PloS One 5: e11289 
  35. Perez-Dorado I, Gonzalez A, Morales M, Sanles R, Striker W, Vollmer W, Mobashery S, Garcia JL, Martinez-Ripoll M, Garcia P, Hermoso JA (2010) Insights into pneumococcal fratricide from the crystal structures of the modular killing factor LytC.Nature Structural & Molecular Biology 17: 576-581 
  36. Perez-Dorado I, Sanles R, Gonzalez A, Garcia P, Garcia JL, Martinez-Ripoll M, Hermoso JA (2010) Crystallization of the pneumococcal autolysin LytC: in-house phasing using novel lanthanide complexes.Acta crytallographica Section F, Structural Biology and Crystallization Communications 66: 448-451 
  37. Ribes S, Adam N, Ebert S, Regen T, Bunkowski S, Hanisch UK, Nau R (2010) The viral TLR3 agonist poly(I:C) stimulates phagocytosis and intracellular killing of Escherichia coli by microglial cells.Neuroscience Letters 482: 17-20 
  38. Ribes S, Ebert S, Regen T, Agarwal A, Tauber SC, Czesnik D, Spreer A, Bunkowski S, Eiffert H, Hanisch UK, Hammerschmidt S, Nau R (2010) Toll-like receptor stimulation enhances phagocytosis and intracellular killing of nonencapsulated and encapsulated Streptococcus pneumoniae by murine microglia.Infection and Immunity 78: 865-871
  39. Ribes S, Ebert S, Regen T, Czesnik D, Scheffel J, Zeug A, Bunkowski S, Eiffert H, Hanisch UK, Hammerschmidt S, Nau R (2010) Fibronectin stimulates Escherichia coli phagocytosis by microglial cells.Glia 58: 367-376 
  40. Ruiz-Cruz S, Solano-Collado V, Espinosa M, Bravo A (2010) Novel plasmid-based genetic tools for the study of promoters and terminators in Streptococcus pneumoniae and Enterococcusfaecalis.Journal of Microbiological Methods 83: 156-163 
  41. Sadowy E, Kuch A, Gniadkowski M, Hryniewicz W (2010) Expansion and evolution of the Streptococcus pneumoniae Spain9V-ST156 clonal complex in Poland.Antimicrobial Agents and Chemotherapy 54: 1720-1727 
  42. Silva-Martin N, Molina R, Angulo I, Mancheno JM, Garcia P, Hermoso JA (2010) Crystallization and preliminary crystallographic analysis of the catalytic module of endolysin from Cp-7, a phage infecting Streptococcus pneumoniae. Acta Crystallographica Section F, Structural Biology and Crystallization Communications 66: 670-673 
  43. Zahlten J, Steinicke R, Opitz B, Eitel J, N'Guessan P D, Vinzing M, Witzenrath M, Schmeck B, Hammerschmidt S, Suttorp N, Hippenstiel S (2010) TLR2- and nucleotide-binding oligomerization domain 2-dependent Kruppel-like factor 2 expression downregulates NF-kappa B-related gene expression.Journal of Immunology 185: 597-604 
  44. Carrolo M, Pinto FR, Melo-Cristino J, Ramirez M (2009) Pherotypes are driving genetic differentiation within Streptococcus pneumoniae.BMC Microbiology 9: 191 
  45. Lorenzo-Diaz F, Espinosa M (2009) Lagging-strand DNA replication origins are required for conjugal transfer of the promiscuous plasmid pMV158.Journal of Bacteriology 191: 720-727
  46. Lorenzo-Diaz F, Espinosa M (2009) Large-scale filter mating assay for intra- and inter-specific conjugal transfer of the promiscuous plasmid pMV158 in Gram-positive bacteria.Plasmid 61: 65-70

Partners

 

Helmholtz Centre for Infection Research

RWTH Aachen, Germany

National and Kapodistrian University of Athens, Greece

National Medicines Institute, Poland

Instituto de Medicina Molecular, Portugal

Hospital de Pediatría "Prof. Dr. Juan P. Garrahan", Argentina

Post Graduate Institute of Medical Education and Research, India

University of Glasgow, UK

Consejo Superior de Investigadones Científicas, Spain

Ernst Moritz Arndt University, Greifswald, Germany

University Miguel Hernández, Spain

University Hospital, Basel

Protea Vaccine Technologies Ltd.

Groups

Coordinator

Helmholtz Centre for Infection Research

Funding agency

EU-Projects

EATRIS

The European Advanced Transnational Research InfraStructure in Medicine

Medical translation of basic research discoveries into clinical applications has turned out to be a major challenge for the European research area. A major bottleneck is the fragmented nature of basic and clinical research infrastructure, leading to unnecessary delays and difficulties in drug development or the implementation of new diagnostic strategies.
EATRIS – European Advanced Translational Research InfraStructure in Medicine – is a strategic EU project that aims to offer a research infrastructure to help overcome bottlenecks currently hampering the transfer both of basic research findings into clinical application and of clinical observations to basic research. In a unique partnership, governmental and scientific organisations form the EATRIS consortium to develop a master plan for setting up the provision of an infrastructure on a European level. The EATRIS idea is to organize under one roof multidisciplinary, creative work atmosphere, open labs, comprehensive modern equipment, scientific and legal expertise with central facilities and services and a translational research curriculum.
EATRIS will enable a faster and more efficient translation of research findings into the development of innovative strategies for the prevention, diagnosis and treatment of diseases which are of particular relevance for European member states and that have a high medical and economic burden.

Partners

 

University of Copenhagen, Cluster for Molecular Imaging (CMI), Denmark

Institute for Molecular Medicine Finland (FIMM), Finland

German Cancer Research Centre (DKFZ), Germany

Helmholtz Centre for Infection Research (HZI), Germany

Istituto Superiore di Sanità (ISS), Italy

Centre for Translational Molecular Medicine (CTMM), The Netherlands

University of Oslo (UiO), Norway

University Hospital Vall d'Hebron (FIR-HUVH), Spain

Groups

Speaker

Regina Becker

Coordinator

Helmholtz Centre for Infection Research (DE)

Funding agency

EU-Projects

EU-OPENSCREEN

European Infrastructure of Open Screening Platforms for Chemical Biology

EU-Openscreen 2012EU-OPENSCREEN, the European Infrastructure of Open Screening Platforms for Chemical Biology, integrates high- throughput screening platforms, chemical libraries, chemical resources for hit discovery and optimisation, bio- and cheminformatics support, and a database containing screening results, assay protocols, and chemical information.
These platforms – offering the most advanced technologies – will be used by European researchers from academia and SMEs in order to identify compounds affecting new targets. Open access to an integrated infrastructure for Chemical Biology will thus satisfy the needs for new bioactive compounds in many fields of the Life Sciences (e.g. human and veterinary medicine, systems biology, biotechnology, agriculture and nutrition).

Partners

 

Research Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM)

Institute of Molecular Genetics AS CR (IMG)

Technical University of Denmark (DTU)

European Molecular Biology Laboratory – Outstation European Bioinformatics Institute (EBI)

Institute for Molecular Medicine Finland (FIMM)

CNRS - Délégation Alsace

Leibniz-Institut für Molekulare Pharmakologie (FMP)

Helmholtz-Zentrum für Infektionsforschung (HZI)

Max Delbrück Center for Molecular Medicine (MDC)

Interdisciplinary Center for Biomolecular Studies and Industrial Applications (CISI)

IRBM for Collezione Nazionale di Composti Chimici e Centro Screening (CNCCS)

Biomedical Research Foundation, Acadamy of Athens (BRFAA)

Netherlands Cancer Institute (NKI)

Universitet i Oslo (UiO)

Institute of Medical Biology of PAS (IMB)

Fundacio Privada Parc Cientific de Barcelona (PCB)

Institute of Chemistry Timisoara of Romanian Academy (ICT)

Umeå University (UmU)

Universiteit Ghent

Speaker

Ronald Frank

Coordinator

Foschungsverbund Berlin e.V. (FMP)(DE)

Funding agency

EU-Projects

Heptromic

Genomic predictors and oncogenic drivers in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers, and is a major health problem. Its incidence is growing and with more than 700,000 annual cases worldwide -50,000 in Europe-, it is the 3rd cause of cancer-related mortality. Most patients are diagnosed at advanced stages with dismal survival rates lower than 1 year, even after sorafenib, the sole systemic therapy available. The main goal of the HEPTROMIC project is to produce breakthrough knowledge in two critical aspects of HCC research: prognostic prediction and identification of oncogenic drivers susceptible for intervention, leading towards more personalized treatment algorithms. The HEPTROMIC Consortium proposes a 3-year translational research study bringing together an outstanding team of researchers with clinical and genomic expertise along with cutting-edge technology. Eight partners -six academic and two SMEs- will address the following objectives by applying high-end transcriptome, methylome and deep sequencing technology in a large set of 1,140 human samples: Objective 1) Genomic characterization of poor prognosis subclass of hepatocellular carcinoma. Objective 2) Identification of driver oncogenic events as potential treatment targets. Findings obtained will be confirmed in sophisticated experimental models that closely mimics human liver cancer. Objective 3) Design of prognostic devices for clinical translation. This transfer of knowledge will be led by SMEs with entrepreneurial management skills with experience in creating new products increasing European competitiveness and boosting the innovative capacity of industries. Overall, the Consortium foresees impacts on improved patient survival by refining prognosis and decision-making, identifying targets amenable for selective therapies and by improving the allocation of resources. In summary, HEPTROMIC will strength links between the academic and industry spheres, ultimately contributing to reduce liver cancer mortality. 

Partners

 

Institut D’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). Barcelona, Catalonia, Spain

Institut National de la Santé et de la Recherche Médicale (INSERM). Paris, France

Fundació Privada Institut d'Investigació Biomèdica de Bellvitge (IDIBELL). Barcelona, Catalonia, Spain

Helmholtz Zentrum Für Infektionsforschung (HZI). Braunschweig, Germany

Fondazione IRCCS Istituto Nazionale dei tumori (INT). Milan, Italy

Broad Institute, Harvard. Boston, USA

Diagenode. Liège, Belgium

TcLand Expression SA. Nantes, France

Leader

Groups

There are no results

Speaker

Lars Zender

Coordinator

Consorci Institut D’Investigacions

Funding agency

EU-Projects

NOPERSIST

Novel strategies for the prevention and control of persistent infections

Persistent infections such as Human Immunodeficiency Virus (HIV), tuberculosis´(TB) in humans and para-tuberculosis (ParaTB)-, mycoplasma- and Haemophilus-infections in farm animals are global health problems of immense social and economic importance . HIV-1 affects about 40 million people and M. tuberculosis infection is even higher world-wide. M. tuberculosis is a slowly replicating bacillus that resides intracellularly within phagosomes of macrophages and commonly causes latent infections of the lung and in about 5% of the infected individuals it leads to active disease. Co-infection with M. tuberculosis is estimated in about one-third of HIV-1 infected subjects. Indeed, the risk of developing M. tuberculosis as an opportunistic infection is increased up to 200-fold in HIV-1 + subjects. Globally, there are more than 14 million persons dually infected with TB and HIV. Drug resistance to HIV-treatment and appearance of multiple-drug resistance (MDR) and off late of Extra-Drug Resistance (XDR) strains of M. tuberculosis , the causative agent of human TB is steadily leading to a hopeless situation as far as the therapy is concerned. To make things worse, there is no effective vaccine available against HIV. M. bovis BCG, the only vaccine available against TB, has shown highly variable efficiency and has been very often ineffective. Its use has been discontinued in several countries. John’s diseases or para-tuberculosis is a chronic , debilitating entritis of ruminants leading to serious production-limiting consequences world-wide. Similarly, procine respiratory infections caused by Mycoplasma and Haemophilus species are emerging pathogens already causing massive economic losses to the European pig industry which have been estimated to be in excess of 1 billion Euro per year. Diagnostics of all the these infections mentioned above is extremely difficult and time-consuming and no efficient, cost effective tests are available for an early diagnosis of these infections. 

Partners

 

Unternehmen

LIONEX Diagnostics & Therapeutics GmbH (Coordinator),

Vichem Chemie Research Ltd,

Prionics AG,

Gesellschaft für Innovative Veterinärdiagnostik mbH,

Staatliche Forschungeinrichtungen

Animal Health and Veterinary Laboratories Agency,

Karolinska Institutet

Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol,

University of Florence,

Prince Leopold Institute of Tropical Medicine

Leader

Groups

Speaker

Rolf Müller

Coordinator

LIONEX (DE)

Funding agency

EU-Projects

TRANSVAC

European Network of Vaccine Research and Development

TRANSVAC aims to accelerate the pharmaceutical and clinical development of promising vaccine candidates by bridging the gap between academic research and clinical trails through carefully managing the advancement of promising vaccine candidates from preclinical animal experiments to early proof-of principle studies in humans. Transvac will be the European driving force for vaccine development and will be open and accessible to those interested parties, who are capable of contributing key elements of the strategy, allowing them to leverage the value of the whole consortium. This consortium will comprise the major European stakeholders with an interest in vaccine development, from the scientific community in Europe to the European vaccine manufacturers. 

Partners

 

European Vaccine Initiative (EVI), Germany

Biomedical Primate Research Centre (BPRC), The Netherlands

Helmholtz Centre for Infection Research (HZI), Germany

Vakzine Projekt Management GmbH (VPM), Germany

LIONEX GmbH, Germany

ID-Lelystad (IDL), The Netherlands

UK Health Protection Agency, Centre for Emergency Preparedness and Response (CEPR, formerly CAMR), UK

UK Health Protection Agency, National Institute for Biological Standards and Control (NIBSC), UK

Max Planck Institute for Infection Biology (MPIIB), Germany

University of Regensburg (UREG), Germany

London School of Hygiene & Tropical Medicine (LSHTM), UK

University of Oxford, The Jenner Institute  (UOXF), UK

University of Lausanne (UNIL), Switzerland

TuBerculosis Vaccine Initiative (TBVI), The Netherlands

Leader

Groups

Speaker

Carlos Guzman

Coordinator

European Vaccine Initiative (DE)

Funding agency

EU-Projects

EMTRAIN

European Medicines Research Training Network

The European Medicines Research Training Network (EMTRAIN) will establish a sustainable, pan-European platform for education and training (E&T) covering the whole life-cycle of medicines research, from basic science through clinical development to pharmacovigilance.

This will be achieved by integrating the strengths and competencies of the ESFRI BMS Infrastructures, the EFPIA companies, the current and future IMI E&T programmes as well as other scientific projects.

Partners

EFPIA Partners

AstraZeneca
Genzyme
Novartis
Bayer
Pfizer
Roche
GSK, GlaxoSmithKline Research and Development Ltd.
UCB
Novo Nordisk
Sanofi
Boehringer Ingelheim
Janssen Pharmaceutica
Orion
Almirall
Lundbeck
Esteve

 

Public Partners

MUW (ECRIN partner)
Karolinska Institute (EATRIS partner)
KUH (ECRIN partner)
UniMan (BBMRI partner)
Inserm (ECRIN partner)
EMBL-EBI (ELIXIR partner)
MUG (BBMRI partner)
GIE-CERBM (Infrafrontier partner)
HMGU (Infrafrontier partner)
UOX (Instruct partner)
MRC-HU (ECRIN partner)
HZI (EATRIS partner)

Speaker

Rebecca Ludwig

Coordinator

AstraZeneca (SE)

Funding agency

EU-Projects

OPTISTEM

Optimization of Stem cell Therapy for degenerative Epithelial and Muscle Diseases

OptiStem is an EU-funded research project that brings together stem cell biologists and clinical experts from across Europe investigating stem cells in skeletal muscle and epithelia. OptiStem combines basic research about stem cells with pre-clinical work and clinical trials. All these areas of research are vital to understand how to use stem cells in the fight against disease. It will be investigated how stem cells could be used to treat degenerative diseases that damage skeletal muscle or epithelia such as skin or the surface of the eye.

Partners

 

France

Institut nationale de la santé et de la recherche médicale (INSERM)

Pasteur Institute

Germany

Helmholtz Centre for Infection Research

Miltenyi Biotec GmBH

Italy

E. Medea Scientific Institute

FIRC Institute of Molecular Oncology Foundation

MolMed S.p.A.

San Rafaelle del Monte Tabor Foundation

University of Milan

University of Modena

Spain

University Pompeu Fabra

Switzerland

Centre Hospitalier Universitaire Vaudois CHUV

Ecole Polytechnique Fédéral de Lausanne

UK

Cancer Research UK

Dando & Colucci LLC

King’s College London

University of Edinburgh

University of Oxford

Speaker

Regina Becker

Coordinator

University of Milan (IT)

Funding agency

EU-Projects

INFRAFRONTIER

The European infrastructure for phenotyping and archiving of model mammalian genomes

Logo INFRAFRONTIERThe European infrastructure for phenotyping and archiving of model mammalian genomesMedically related Life Sciences use the mouse as a model system to understand the molecular basis of health and disease in humans. An essential task for Biomedical Sciences in the 21st century will be the functional analysis of mouse models for every gene in the mammalian genome. More than 30000 mutations in ES cells and numerous genetic reference populations consisting of thousands of inbred mouse strains with segregating genetic backgrounds will be engineered and thousands of mouse models for human diseases will become available over the next years by the collaborative efforts of the International Mouse Knockout Consortium.

The major bottlenecks identified by the user community will be proper characterization (Mouse Clinics), archiving and dissemination of mouse disease models to the research laboratories. The current capacities, governance structures and funding strategies of existing infrastructures will not be able to serve the upcoming urgent needs. Existing facilities across Europe can only offer capacity for the analysis and dissemination of a few hundred disease models per year.  

Thus it is imperative to organize and establish now an efficient distributed infrastructure for the phenotyping, archiving and dissemination of mouse models on a well-concerted, large-scale and pan-European level. This will be a prerequisite for maintaining Europe's leading role in the functional annotation of the mouse genome. Infrafrontier will guarantee the accessibility of mouse models and will be essential to facilitate their exploitation.

Infrafrontier is an Integrated Project of the 7th Framework Programme of the European Commission, comprising 7 work packages, 9 countries and 14 partners.

WP5 – Draft Engineering Specifications

Prof. Dr. Klaus Schughart, Helmholtz Centre for Infection Research

Objectives

1) Development of detailed specifications for designing and building or upgrading of mouse holding and breeding facilities, archiving and distribution facilities and mouse phenotyping facilities.

2) To document these specifications in a formal publication.

 

Partners

 

Ministries and research councils

Leader

Groups

Coordinator

Prof. Dr. Martin Hrabé de Angelis, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg/München, Germany

Funding agency

EU-Projects

BACSIN

Bacterial abiotic cellular stress and survival improvement network

BACSIN is a 16-member consortium with the main focus to improve rational exploitation of the catalytic properties of bacteria for the treatment and prevention of environmental pollution. Current application of bacteria in the environment is hindered by the lack of knowledge on the effects of stresses on cellular activity, most importantly abiotic stresses prevailing on site (e.g., desiccation or nutrient starvation), stresses as a result of pollution itself (e.g., toxicity), and those during strain preparation and formulation.
BACSIN proposes four iterative poles of research and technology to overcome this hindrance for subsequent improved microbial usage. The 1st pole will investigate genome-wide catabolic and stress expression in a set of different pollutant degrading bacteria (the BACSINs ). Key cellular factors and regulatory networks determining the interplay between stress-survival and pollutant catabolism will be unveiled, and faithful predictive models for cell behaviour produced. The 2nd pole will study stress resistance, survival and activity of BACSINs in real polluted environments, via microcosms and in situ traps, plant roots and leaves, while accentuating possible effects on native communities.

 

Partners

 

UNIL - University of Lausanne (UNIL), Department of Fundamental Microbiology, Lausanne, Switzerland

BIRD - Bio-Iliberis R&D, Armilla (Granada), Spain

CSIC - Consejo Superior de Investigaciones Científicas (CSIC),
Centro Nacional de Biotecnología (CNB), Madrid, Spain

ETCZ - Aecom, Prague, Czech Republic

UGOT - Götebourg Universitet,
Department of Cell and Molecular Biology, Göteborg, Sweden

HZI - Helmotz-Zentrum für Infektionsfonsforschung GmbH,
Department: Microbial Interactions and Processes, Braunschewig, Germany

KULeuven - Katholieke Universiteit Leuven,
Department of Earth and Environmental Sciences, Heverlee, Belgium

NIOO-KNAW - Netherlands Institute of Ecology (NIOO-KNAW), Heteren
The Netherlands

SLU - Swedish University of Agricultural Sciences,
Uppsala BioCenter, Department of Microbiology, Uppsala, Sweden

TUBS - Carolo-Wilhelmina Technische Universität zu Braunschweig,
Institute of Microbiology, Braunschweig, Germany

UFZ - Helmholtz Centre for Environmental Research - UFZ,
Department Bioremediation, Leipzig, Germany

VU - Vrije Universiteit Amsterdam,
Department Molecular Cell Physiology, Amsterdam, The Netherlands

WU - Wageningen Universiteit, Laboratory of Microbiology,
Wageningen, The Netherlands


EC-JRC - European Union Represented by the European Commission-
Joint Research Centre, Institute for Environment and Sustainability, Ispra (VA), Italy

Belair - Remy Enga Luye, Belair Biotech SA, Geneva, Switzerland

ECO - Ekoloski inzenjering d.o.o., Kukci Nova Vas, Croatia

Leader

Groups

Speaker

Dietmar Pieper

Coordinator

Université de Lausanne (CH)

Funding agency

EU-Projects

FAST-XDR-DETECT

Development of a two-approach plate system for the fast and simultaneous detection of MDR and XDR M.tuberculosis

Tuberculosis (TB) continues being a leading cause of death due to a single infectious disease agent. The HIV/AIDS pandemic and the emergence of drug resistance are compounding factors that hinder the control of the disease. Associated with the problem of drug resistance is the emergence of multidrug-resistant (MDR) strains of Mycobacterium tuberculosis, defined as strains resistant to at least isoniazid and rifampicin, the most valuable drugs in the treatment of the disease. More recently, the appearance of extensively drug resistant (XDR) strains has been reported. These strains, in addition to being MDR, are also resistant to key second-line drugs. Patients, especially HIV patients, harbouring XDR strains have virtually no treatment options. New and improved methods for fast detection of drug resistance are urgently needed. This project will develop a twofold-approach system for the fast and simultaneous detection of MDR and XDR strains based on a rapid phenotypic assay and a genotypic test. Colorimetric methods - which have been previously validated by our group for first-line drug susceptibility testing - will be set up for key second-line drugs involved in XDRTB. The molecular method will be based on a modification of the novel technology named detection of immobilized amplified product in one phase system. This versatile molecular approach   - which in a previous EU project proved reliable and user-friendly for the detection of rifampicin resistance - will be further improved and set up for the detection of MDR strains. The developed tools will be then validated in different settings and prospectively evaluated in target populations. The project will contribute to the currently available tools for rapid detection of drug resistant TB and will introduce new tools for the detection of the recently-described and highly-lethal XDRTB. It will also contribute to our knowledge on the mechanisms of M. tuberculosis resistance to second-line anti- drugs.
 

Partners

 

Prince Leopold Institute of Tropical Medicine, Belgium

Helmholtz Zentrum für Infektionsforschung GmbH, Germany

Swedish Institute for Infectious Disease Control, Sweden

Lionex GmbH, Germany

Infectology Center of Latvia, Latvia

CorpoGen, Colombia

INEI-ANLIS Inst. Malbrán, Argentina

Hospital Cetrángolo, Argentina

Leader

Groups

There are no results

Speaker

Helmut Blöcker

Coordinator

Prince Leopold Institute of Tropical Medicine (BE)

Funding agency

EU-Projects

PANFLUVAC

Efficacious vaccine formulation system for prophylactic control of influenza pandemics

Influenza epidemics remain a burden to both human health and national economies, as witnessed by the recent advance of pathogenic avian H5N1 influenza virus. While the numbers of human deaths in Europe have remained relatively low, the presence of such cases in Turkey demonstrates the danger posed by this virus. Now that H5N1 virus has been detected in wild birds in Europe, the PANFLUVAC consortium is committed to creating an efficacious vaccine against this virus, to provide strong protection in a pandemic situation.
The overall aim of PANFLUVAC is to construct vaccine delivery systems for intranasal and parenteral vaccines. New H5N1 vaccines are based on a current subunit vaccine construction – for immediate evaluation – as well as well-established virosome technology for future development within the project. Pre-clinical evaluation will also permit comparison of the new intranasal vaccines with whole virus vaccine. The vaccine potency will be enhanced by novel adjuvants – ISCOM, glycolipids and lipopeptide adjuvants biosafe for humans - known to promote the dendritic cell activity critical for efficient induction of immune defences. This approach offers both antigen sparing potential and immunopotentiation characteristics. biosafe for humans. With the ISCOM having been employed with experimental influenza vaccines, this will allow the new H5N1 vaccines to be fast-tracked in their development. Accordingly, PANFLUVAC will generate its first H5N1 vaccine for intranasal evaluation within the first 18 months of the project.
The PANFLUVAC project is also designed to facilitate rapid modification of the vaccine in the face of virus drift. Within the preclinical evaluation, the new vaccines will be tested for the degree of heterotypic cross protection they offer. PANFLUVAC offers a generic vaccine development system to provide safe and efficacious vaccines against influenza, fitting with the “Community Influenza Pandemic Preparedness and Response Planning".

Partners

 

Schweizerische Eidgenossenschaft, Institute of Virology and Immunoprophylaxis (IVI) FDEA/FVO: Federal Veterinary Office of the Federal Department of Economic Affairs

Crucell

National Institute for Biological Standards and Control, (NIBSC)

Retroscreen Virology Ltd

University of Bergen, The Influenza Centre, The Gade Institute

Health Protection Agency, Respiratory & Neurological Virus Laboratory, Respiratory Unit HPA

Istituto Superiore di Sanitá (ISS), Department of Infectious, Immune-mediated and Parasitic Diseases

Helmholtz, Zentrum für infektionsforschung

SCIPROM Scientific Project Management

 

Speaker

Carlos Guzman

Coordinator

Federal Veterinary Office (CH)

Funding agency

EU-Projects

Clinigene

European Network for the Advancement of Clinical Gene Transfer and Therapy

The field of gene therapy has matured and the prospects are exciting and hopeful, particularly since some treatmentshave now been shown to be effective in the clinic. However, precise quality and safety standards for clinical genetransfer have yet to be defined. In this context, defining optimal methods for the production of standard vector systemswould pave the way for accelerated development and improved safety. This would be of enormous value to industry,individual investigators and regulators.The goal of this proposal is the creation of a European Network for the Advancement of Clinical Gene Transferand Therapy (CLINIGENE) integrating multidisciplinary research and development in gene therapy as well asmobilising all major stake holders involved in the development of gene therapy medicinal products: academia,industry, regulatory bodies, clinics and patients. The network will generate platform databases for particular vectorswith respect to their safety and efficacy to ensure product manufacturing according to well-defined quality and safetystandards in order to accelerate clinical trials. This will be achieved by compiling all available information and thenranking test and control methods by comparison, and through validation by expert partners.The joint programme of activities comprises1. Integration activites: sharing facilities, exchange and high-level training of personnel, e-communication andcollaboration with the ESGT.2. Research activities: six horizontal activities serving integration towards the generation of reference/standard profiledata-bases - AAV, γ-retrovirus, lentivirus, adenovirus, genetically-modified cells & non-viral vectors - and fourvertical activities defining a path to optimised clinical protocols - quality and efficacy (manufacture), safety (pharmtoxand virus safety); pre-clinical models and novel assessment tools, clinical trials.3. Dissemination activities: training, high-level education, communication (including a web-site with scientific &medical data-bases) and management of shared information and intellectual property rights.Within a strong integration plan, the Network is planning for flexibility in order to adapt to : (i) progresses recorded ina stepwise manner and (ii) novelty arising during the CLINIGENE workprogramme.

Partners

 

Academic Partners

FCSR-TIGET, San Raffaele Telethon Institute for Gene Therapy, Milano, Italy

Institute of Ophthalmology, University College London,
Div. of Molecular Therapy, London, United Kingdom

TIGEM - Telethon Institute of Genetics and Medicine, Napoli, Italy

Orphanet - INSERM SC11
Hôpital Broussais, Paris, France

Medizinische Hochschule Hannover
Dept. Experimental Hematology, Hannover, Germany

INSERM, France

CBATEG - Autonomeous Univ. of Barcelona, Centre de Biotec. Animal i Teràpia,
Bellaterra, Spain

Academy of Sciences of the Czech Republic,
Institute of Molecular Genetics,
Prague, Czech Republic

IBET - Instituto de Biologia Experimental e Technologica, Oeiras, Portugal

Paul-Ehrlich-Institut, Langen, Germany

Ecole Normale Supérieure de Cachan, Cachan Cedex, France

Royal Holloway & Bedford University, School of Biological Science,
Egham, Surrey, United Kingdom

Mayo Clinic, Molecular Medicine Programme, Rochester, United States

Karolinska Institutet, Department of Medicine, Huddinge University Hospital,
Stockholm, Sweden

Technischen Universität München, Institut für Experimentelle Onkologie und Therapieforschung, München, Germany

Helmoltz Centre for Infection Research, Braunschweig, Germany

Klinik für Neurologie der Universität zu Köln,
Labors für Gentherapie & Molekulares Imaging am MPI für Neurologische Forschung, Köln, Germany

APHP - UMR 7087, UPMC/CNRS-CERVI, Hôpital de la Pitié, Paris, France

University of Ulm, Division of Gene Therapy, Ulm, Germany

Institut de Biotechnologie - Univ. de Lausanne, Lausanne, Switzerland

Genethon, Evry, France

CNRS, UMR 8121, Institut Gustave-Roussy, Villejuif, France

CHU Hotel Dieu Nantes, Laboratoire Therapie Genique, Nantes, France

The Hebrew University, Hadassah Medical School, Jerusalem, Israel

ISTEM (Unité INSERM), Evry Cedex, France

INSERM, Faculté de Sciences Pharma. et Biologiques, Paris, France

German Cancer Research Center (DKFZ), NCT-Heidelberg im Otto-Meyerhof-Zentrum, Heidelberg, Germany

University of Eastern Finland, A.I.Virtanen Institute, Kuopio, Finland

Industry Partners

Bioalliance Pharma, Paris, France

Bioreliance Ltd, Stirling, Scotland, United Kingdom

CellGenix, Freiburg, Germany

CleanCells, Bouffere, France

Epixis, Paris, France

Genosafe, Evry, France

Oxford BioMedica, Oxford

Plasmid Factory, Bielefeld, Germany

Transgene, Strasbourg, France

 

Speaker

Hansjörg Hauser

Coordinator

École normale supérieure de Cachan (F)

Funding agency

EU-Projects

EUMODIC

The European Mouse Disease Clinic: A distributed phenotyping resource for studiying human disease

As a first step towards a comprehensive functional annotation of the mouse genome, EUMODIC will undertake a primary phenotype assessment of up to 650 mouse mutant lines. In addition, a number of the mutant lines will be subject to a more in depth secondary phenotype assessment.
The EUMODIC consortium is made up of 18 laboratories across Europe who are experts in the field of mouse functional genomics and phenotyping and have a track record of successful collaborative research in EUMORPHIA. The EUMODIC consortium will build on the work in the EUMORPHIA project that delivered a comprehensive database ' EMPReSS - of Standard Operating Procedures (SOPs) that can be used to determine the phenotype of a mouse. EUMODIC has developed a selection of these screens, EMPReSSslim, which is structured for comprehensive, primary, high throughput phenotyping of large numbers of mice.
We will also adopt innovative approaches to the generation and assessment of cohorts of age-matched mutants and controls for phenotyping. Primary phenotype assessment using EMPReSSslim will be undertaken in four large-scale phenotyping centres at the GSF, Germany; ICS, France; MRC Harwell, UK and the Sanger Institute, UK. Mutant lines will be made available from another EU initiative, the EUCOMM (European Conditional Mouse Mutagenesis) project which aims to produce conditional mutations in 20,000 mouse genes.
A distributed network of centres with in depth expertise in a number of phenotyping domains will undertake more complex, secondary phenotyping screens and apply them to a subset of the mice which have shown interesting phenotypes in the primary screen. The partners will also develop technologies to refine EMPReSSslim and improve throughput of mouse phenotyping. A key element will be the continued development of bioinformatics resources to store the phenotype information and link them to existing database resources.

Partners

 

MRC Harwell, UK

Institut Clinique de la Souris, France

Helmholtz Zentrum München, Germany

The Wellcome Trust Sanger Institute, UK

Helmholtz-Centre for Infection Research, Germany

National Research Council, Italy

University of Manchester, UK

European Molecular Biology Laboratory Monterotondo, Italy

Spanish National Cancer Research Centre, Spain

Ani.Rhone-Alpes, France

Tel Aviv University, Israel

Autonomous University of Barcelona, Spain

Center for Integrative Genomics, Switzerland

Institut De Transgenose, France

University of Cambridge, UK

Telethon Institute of Genetics and Medicine, Italy

Research Centre "Alexander Fleming", Greece

Groups

Speaker

Andreas Lengeling

Coordinator

MRC Mammalian Genetics Unit (UK)

Funding agency

EU-Projects

ASSIST

Comprehensive approach to understand streptococcal diseases and their sequelae to develop innovative strategies for diagnosis, therapy, prevention and control

Overview

The disease burden of group A streptococcal infections worldwide is extremely high. More than 600 million persons, mostly children, suffer from streptococcal pharyngitis each year. There are 600 thousand cases of invasive disease. More serious are the sequelae of these infections in the form of acute rheumatic fever and rheumatic heart disease. About 15 million children are suffering from rheumatic heart disease, out of these, 6 million in India alone. Streptococcal diseases can be considered as one of the most important groups of neglected
communicable diseases in India. There are many reasons for the inability to control GAS diseases in India. Besides poverty and living conditions, inadequate treatment and noncompliance with penicillin secondary prophylaxis after onset of rheumatic fever have all contributed to the high disease burden. The best perspective for controlling this disease is to develop a fast diagnostic test for rheumatogenic streptococci and to develop a regionspecific vaccine against group A streptococci. Prerequisite for diagnostic and vaccine development is in-depth understanding of streptococcal diseases in Indian scenario. Data on
the epidemiology of all GAS diseases, the characterization of the circulating strains in different regions of India, determination of genetic predisposition markers in different ethnic populations of India and immunological data to identify region-specific vaccine candidates are urgently needed. The major objective of this proposal is to pull together such information in a comprehensive way which will then form the basis of a novel diagnostic test for
rheumatogenic streptococci and for the identification of candidates to develop a regionspecific vaccine, using state-of-the-art technologies already established in Europe. This proposal is the first comprehensive approach to understand streptococcal diseases and would contribute towards solving a major health problem in India.

Project Objectives

The primary objective of this proposal is to apply a multi-disciplinary approach to understanding the spectrum of streptococcal diseases in India. A novel diagnostic test for rheumatogenic streptococci will be designed and candidates for development of region-specific group A streptococcal vaccines prototypes will be identified. A diagnostic test for rheumatogenic streptococci and development of an efficacious vaccine in India has never been attempted so far and is, therefore, a novel feature of this proposal. The specific objectives are:

Objective 1:

Epidemiological studies in defined areas in North and South India

Objective 2:

Genotyping of virulence strains obtained during the survey and expression profiling of representative strains

Objective 3:

Elucidation of nature and mechanisms of invasive diseases in India in comparison to European surveillance data

Objective 4:

Identification of genetic markers that contribute towards susceptibility to streptococcal infections in the two ethnically defined Indian populations

Objective 5:

Validation of the induction mechanisms of acute rheumatic fever in the Indian
scenario

Objective 6:

Rational design of a fast diagnostic test for the identification of streptococci capable of causing rheumatic fever based on the structural biology of collagen recognition

Objective 7:

Identification of candidates to develop region-specific vaccine

Objective 8:

Communication of relevant information, transfer of technology and knowledge on new biotechnological approaches to governments, decision makers, international agencies and health authorities

Objective 9:

Training of young Indian scientists in the modern methodology established at the European partners’ institutes

Partners

 

Helmholtz Centre for Infection Research

Tasks:

  • Coordination & project management
  • Virulence expression profiling of the isolates
  • design of protein arrays
  • identification of region-specific vaccine candidates and testing their efficacy

Project coordinator:

Prof. Dr. G. S. Chhatwal

Helmholtz Centre for Infection Research

Dept. Microbiology

Inhoffenstr. 7

D 38124 Braunschweig

Germany

e-mail: gsc@helmholtz-hzi.de

Team Members:

Dr. Andreas Nerlich, e-mail: Andreas.Nerlich@helmholtz-hzi.de

Dr. Vivek Sagar, e-mail: Vivek.Sagar@helmholtz-hzi.de

Rene Bergmann, e-mail: Rene.Bergmann@helmholtz-hzi.de

Post Graduate Insitute of Medical Education and Research

Tasks:

  • Setting up school-level survey for streptococcal carriage and pharyngitis in defined areas near Chandigarh, North India
  • Setting up surveillance for acute rheumatic fever and rheumatic heart disease in hospitals of survey area
  • Establishing of surveillance for invasive strep disease in tertiary care hospitals of Chandigarh

Project Participant:

Prof. Dr. K. K. Talwar

Dept. of Cardiology

Post Graduate Institute of Medical Education and Research (PGIMER)

Chandigarh - 160 012

India

Tel. 0091-172-274-5062

Fax 0091-172-274-4401

e-mail: kktalwar@sancharnet.in

Christian Medical College

Tasks:

  • Establishment of a school survey system for the isolation, identification and characterization of GAS strains causing throat and skin infections in a highly endemic community
  • Establishment of a Registry for GAS disease and the strains causing them in a highly endemic south Indian community of school going children
  • Establishment of a hospital based Registry for GAS invasive disease in South India to determine their prevalence and the nature of strains causing them

Project Participant:

Prof. K. Brahmadathan

Dept. of Microbiology

Christian Medical College (CMC)

Vellore – 632 004

India

Tel. 0091-416-228-3085

Fax 0091-416-223-2103

e-mail: knb1948@hotmail.com

Karolinska Institute

Tasks:

  • Comparison of the nature of invasive streptococcal disease in relation to European data
  • Determination of host-pathogen interplay at the local site of infection
  • Determination of host humoral immunity in relation to disease manifestation
  • Identification of molecular mechanisms of streptococcal invasive diseases in India

Project Participant:

Prof. Anna Norrby-Teglund

Dept. of Medicine

Karolinska Institutet (KI)

SE-14186 Stockholm

Sweden

Tel. 0046-858-87296

Fax 0046-8746-7637

e-mail: Anna.Norrby-Teglund@ki.se

All India Institute of Medical Sciences

Tasks:

  • Establishing parameters of disease susceptibility in two patient cohorts with different ethnic backgrounds
  • Comparison of the disease associated MHC haplotypes between invasive disease and patients with rheumatic fever/ rheumatic heart disease
  • Understanding molecular mechanisms of genetic predisposition in streptococcal disease in India

Project Participant:

Prof. Dr. N. K. Mehra

Dept. of Transplant Immunology and Immunogenetics

All India Institute of Medical Sciences (AIIMS)

Ansari Nagar

New Delhi – 110 029

India

Tel. 0091-11-265-88588

Fax 0091-11-265-88663

e-mail: narin98@hotmail.com

University of St. Andrews

Tasks:

  • Analysis of the interaction of collagens with streptococcal surface components to select candidates for structural studies
  • structural analysis of collagen binding to streptococcal peptides
  • design and development of a fast diagnostic prototype assay for rheumatogenic streptococci based on collagen aggregation

Project Participant:

Dr. U. Schwarz-Linek

Centre for Biomolecular Sciences

University of St. Andrews

St Andrews – KY16 9AJ

United Kingdom

Tel. 0044-1334-463401

e-mail: us6@st-andrews.ac.uk

 

Groups

There are no results

Coordinator

Helmholtz-Zentrum für Infektionsforschung

Funding agency

EU-Projects

PROBACTYS

Programmable Bacterial Catalysts

The project aims at constructing of a functioning, streamlined bacterial cell devoid of most of its genome and endowed with a series of highly coordinated, newly assembled genetic circuits for the biotransformation of a range of chloroaromatics into high added value compounds and that would include (although not necessarily in this order or all together) circuits for synchronized behaviour, noise minimisation, low-temperature biocatalysis and/or light-powered and, in addition, amenable to directed, accelerated evolution so that the function of each or some of the individual circuits can be optimised. This will be tested for the production of high added value compounds from chloroaromatics in bioreactors. By achieving such constructs as a proof-of-principle, it is aimed at establishing a solid, rational framework for the engineering of cells performing effectively and efficiently specific functions of biotechnological, environmental or medical interest. This encompasses the production of series of different, versatile circuits and corresponding components that can be used as building blocks in circuit engineering. The proposed workflow includes several work packages, each of which intertwining mathematical modelling with wet-lab experimental work as an integral module. PROBACTYS is a pioneering, concerted European effort towards the development of a Synthetic Biology framework and with a strong focus on the translation of emerging knowledge in biology, engineering and information technology to the development of new processes of biotechnological relevance.

Speaker

Vitor Martins dos Santos

Coordinator

Helmholtz Centre for Infection Research (DE)

Funding agency

EU-Projects

HEALTHY WATER

Assessment of human health impacts from emerging microbial pathogens in drinking water by molecular and epidemiological studies

The overall goal of the project is to advance our knowledge on pathogenesis of emergent microbial pathogens in drinking water and to understand their transmission to humans. The project will focus on all major types of pathogens, i.e. viruses, bacteria and protozoa, and will concentrate on a representative set of European drinking water supply systems and source waters of specific sensitivity to human health. This project will build on the output of the MicroRisk project by focussing on water systems that are in general not as well protected as the systems within MicroRisk. To reach the overall goal the following detailed objectives are approached: 1. Validation and application of detection technologies for emerging microbial pathogens based on nucleic acids. 2. Molecular survey and comparative detailed study of emerging pathogens in European drinking water sources and supply systems. 3. Understanding the human health impact of emerging pathogens by primary epidemiological studies targeted at specific systems and pathogens. 4. Determination of epidemiological correlations with molecular and environmental data and assessment of risk for waterborne microbial infections in Europe. An integrated research approach will be pursued to achieve these objectives by combining molecular and classical detection, activity assessment and epidemiological understanding of emerging pathogens in a specific set of drinking water systems from different European regions. The project will generate validated detection technologies for the targeted waterborne pathogens and reveal possible routes of transmission to humans via drinking water consumption. This new knowledge will provide guidance to improve the hygienic quality of European drinking water supplies and reduce the burden of waterborne infections for the people in Europe.

Strategic objective

According to the work programme of the European Commission in priority 1.1.5 “Food quality and safety” for Topic T5.4.8.3: “Pathogens in drinking water sources”, the following strategic aim is given: “The objective is to gather knowledge on emergent microbial pathogens in drinking water sources. Human health impacts of emergent micro-organisms should be further investigated.”

Project Summary

The overall goal of the project is to advance our knowledge on pathogenesis of emergent microbial pathogens in drinking water and to understand their transmission to humans. The project will focus on all major types of pathogens, i.e. viruses, bacteria and protozoa, and will concentrate on a representative set of European drinking water supply systems and source waters of specific sensitivity to human health. This project will build on the output of the MicroRisk project by focussing on water systems that are in general not as well protected as the systems within MicroRisk. To reach the overall goal the following detailed objectives are approached: 1. Validation and application of detection technologies for emerging microbial pathogens based on nucleic acids. 2. Molecular survey and comparative detailed study of emerging pathogens in European drinking water sources and supply systems. 3. Understanding the human health impact of emerging pathogens by primary epidemiological studies targeted at specific systems and pathogens. 4. Determination of epidemiological correlations with molecular and environmental data and assessment of risk for waterborne microbial infections in Europe. An integrated research approach will be pursued to achieve these objectives by combining molecular and classical detection, activity assessment and epidemiological understanding of emerging pathogens in a specific set of drinking water systems from different European regions. The project will generate validated detection technologies for the targeted waterborne pathogens and reveal possible routes of transmission to humans via drinking water consumption. This new knowledge will provide guidance to improve the hygienic quality of European drinking water supplies and reduce the burden of waterborne infections for the people in Europe.

Project objectives

To meet the general aim given by the Commission we have defined the following specific objectives within the HEALTHY-WATER project:

Objective 1: 

Development and validation of molecular detection technologies

for emerging microbial pathogens based on nucleic acids to provide a format

ready for mass application in drinking water samples

Objective 2: 

Molecular survey and comparative detailed study

of emerging microbial pathogens in European drinking water sources and

supply systems

Objective 3: 

Understanding human health impacts of emerging pathogens

in different drinking water  supply systems and different supply regimes

Objective 4: 

Determination of epidemiological correlations

with molecular and environmental data and assessment of risk for emerging

waterborne microbial infections in Europe 

Workplan

An integrated research approach (see Figure 1 below) will be pursued comprising the following elements: i) molecular detectionand activity assessment of emerging microbial pathogens in source water and supply systems for drinking water from different European regions, ii) prospective epidemiological studies and immunological surveys in targeted areas and of selected pathogens, iii) development of epidemiological models and iv) derivation of public health measures for drinking water in Europe. This integrated approach will be supported by data mining for knowledge about the targeted pathogens, electronic knowledge management and specific searches for epidemiological data from the European regions of relevance. In addition, molecular technologies based on DNA micro-arrays and fingerprints for detection and activity assessment of the emerging pathogens will be validated to allow rapid molecular analyses of many water samples.

Partner

HZI- Helmholtz Centre for Infection Research

Expertise:

  • Coordination & project management
  • molecular analysis of aquatic microbial communities
  • detection of virulence genes and pathogenic bacteria

Project coordinator:

Dr. Manfred G. Höfle
Helmholtz Centre for Infection Research
Dept. Vaccinology
Inhoffenstr. 7
38124 Braunschweig
Germany

E-Mail: Manfred.Hoefle@helmholtz-hzi.de
Website: www.helmholtz-hzi.de/healthy-water

Team Members:

Dr. Ingrid Brettar (second contact person for coordination) 
E-Mail: Ingrid.Brettar@helmholtz-hzi.de 

Prof. Carlos A. Guzman 
Leila Matter
Julia Bötel

UEA - University of East Anglia

Expertise:

  • epidemiology of water and foodborne diseases
  • molecular parasitolgy, analysis of virulence factors in protozoal waterborne pathogens

Project Participant:

Prof. Paul R. Hunter
School of Medicine
Health Policy and Practice
University of East Anglia
Norwich NR4 7TJ England

E-Mail: paul.hunter@uea.ac.uk

Team Members:

Dr. Kevin Tyler
Helen Risebro

IAD - International Association for Danube Research

  • communication with water works and consumers 
  • sampling strategy
  • data base provision

 

Project Participant:

Dr. Georg Kasimir
International Association for Danube Research (IAD)
Societas Internationalis Limnologiae 
c/o Federal Agency of Water Management
Dampfschiffhaufen 54
1220 Vienna, Austria
e-mail: dkasimir@gmail.com

URV - University Rovira i Virgili

  • reference laboratory on hygienic quality of drinking water
  • Hazard Analysis of Critical Control Point for Drinking Water (HACCP)

Project Participant:

 

Prof. Maria-José Figueras
Universitat Rovira Virgii I
Unitat de Microbiologia
Dept. De Ciències Bàsiques
Facultat de Medicina
Sant Llorenç, 21
E-43201 Reus

e-mail: mjfs@correu.urv.es

UB - University of Barcelona

  • analysis of water- and foodborne viruses 
  • molecular detection of microorganisms without cultivation 

Project Participant:

 

Prof. Albert Bosch
Dep. Microbiologia
Universitat de Barcelona
Av. Diagonal 645
E 08028 Barcelona
e-mail: abosch@ub.edu
web: http://www.ub.edu/microbiologia/viruse/index.htm

Team Members: 
Dr. Rosa Pinto
Umai Perez

SUEZ - SUEZ Environnement

  • managment of Drinking Water Supply Systems (DWWS) 
  • molecular detection of waterborne pathogens (generic concentration, micro-array technology, real-time PCR)

Project Participant:

 

Dr. Sophie Courtois
SUEZ Environnement - CIRSEE
38 rue du president Wilson
F78230 Le Pecq France
e-mail: sophie.courtois@suez-env.com
web: http://www.suez-environnement.com/

Team Members:

Kalissa Sebti

NIEH - National Institute of Environmental Health

  • Monitoring and detection of of Cryptosporidia and Giardia by immunomagnetic separation and immune fluorescence 
  • Public health issues and regulatory measures against waterborne infections

Project Participant:

 

Dr. Andrea Török Tamásné
National Center of Public Health
National Institute of Environmental Health
POB 26
1450 Budapest
Hungary
e-mail: toroka@okk.antsz.hu
web: http://efrira1.ansz.hu/oki

Team Members:

Dr. Rita Vasdinyei 
Orsolya Kis 
Aniko Kis 
Judit Plutzer 
Maria Asztalos
Klarissza Domokos 
Zsigmondné Boros

UNSA - Université de Nice Sophia Antipolis

  • bioinformatics of nucleic acids (primer and probe design)
  • electronic management and data base support (e-dashboard, central data bases)

Project Participant:

Prof. Richard Christen 
UNSA - CNRS UMR 6543 & Université de Nice Sophia Antipolis
Laboratoire de Biologie Virtuelle
Centre de Biochimie
Parc Valrose
F06108 Nice
e-mail: christen@unice.fr
Web site: http://bioinfo.unice.fr

Team Members:
Dr. Olivier Croce
Thierry Philipps

MDC- Molecular Diagnostics Center

  • molecular typing of microorganisms
  • provision of reference strains and nucleic acids

Project Participant:

Dr. Antonio Martinez-Murcia
MDC- Molecular Diagnostics Center
Crta. Ncnal. 340, Apdo. 169, 
Orihuela
Spain
e-mail: ammurcia@mdc-bt.com
Web: www.mdc-bt.com

Team Members:

Dr. Maria José Saavedra 
Dr. Remedios Oncina 
Marisa Sousa

Publications

Kahlisch, L. K. Henne, L. Gröbe, I. Brettar and M.G. Höfle; (2012). Assessing the species composition of viable bacteria in drinking water using Fluorescence Activated Cell Sorting (FACS) and community fingerprinting. Microbial Ecol.: 63, 383-397

Henne, K., L. Kahlisch, I. Brettar and M.G. Höfle; (2012). Comparison of structure and composition of bacterial core communities in mature drinking water biofilms and bulk water of a local network. Appl. Environ. Microbiol.: 78, published ahead of print, 2 March, doi:10.1128/AEM.06373-11 PubMed

Pérez-Sautu U., D. Sano, S. Guix, G. Kasimir, R. M. Pintó and A. Bosch; (2012). Human norovirus occurrence and diversity in the Llobregat river catchment, Spain. Environ. Microbiol.: 14, 494-502 PubMed

Figueras M.J., A. Alperi, R. Beaz-Hidalgo, E. Stackebrandt, E. Brambilla, A. Monera and A. J. Martinez-Murcia; (2011). Aeromonas rivuli sp. nov., isolated from the upstream region of a karst water rivulet. Int. J. Syst. Evol. Microbiol.: 61, 242-248 PubMed

Collado L., A. Levican, J. Perez and M. J. Figueras; (2011). Arcobacter defluvii sp. nov., isolated from sewage samples. Int. J. Syst. Evol. Microbiol.:, 2155-2161 PubMed

Collado, L., G. Kasimir , U. Perez, A. Bosch, R. Pinto, G. Saucedo,J. M. Huguet, and M. Jose Figueras; (2011). Occurrence and diversity of Arcobacter spp. along the LlobregatRiver catchment, at sewage effluents and in a drinking water treatment plant. Water Res.: 44, 3696-3702 PubMed

Paul R. Hunter, P, R., M. Anderle de Sylor, H. L. Risebro, G. L. Nichols, D. Kay, and P. Hartemann; (2011). Quantitative Microbial Risk Assessment of Cryptosporidiosis and Giardiasis from Very Small Private Water Supplies. Rsik Analysis:, 228-236PubMed

Collado L., and M. J. Figuera; (2011). Taxonomy, Epidemiology, and Clinical Relevance of the Genus Arcobacter. Clin. Microbiol. Rev.: 24, 174-192 PubMed

Croce, O., F. Chevenet and R. Christen; (2010). A New Web Server for the Rapid Identification of Microorganisms. J Microbial Biochem Technol.:, 84-88

Sano, D.; Pintó, R.M.; Omura, T.; Bosch, A.; (2010). Detection of Oxidative Damages on Viral Capsid Protein for Evaluation Structural Integrity and Infectivity of Human Norovirus. Environ. Sci. Technol.: 44 2, 808-812 PubMed

Kahlisch,L.; Henne,K.; Draheim,J.; Brettar,I.; Höfle,Manfred G.*; (2010). High-resolution in situ genotyping of Legionella pneumophila populations in drinking water by multiple-locus variable-number tandem-repeat analysis using environmental DNA. Applied in Environmental Microbiology: 76 18, 6186-6195 HZI repository PubMed

Kahlisch, L.; Henne, K.; Groebe, L.; Draheim, J.; Höfle, M.G.; Brettar, I.; (2010). Molecular analysis of the bacterial drinking water community with respect to live/dead status. Water Science & Technology: WST: 61.1, 9-14

Bouzid M., K. M.Tyle, R. Christen, R. M. Chalmers, K. Elwin, and Paul R Hunter; (2010). Multi-locus analysis of human infective Cryptosporidium species and subtypes using. BMC Microbiol.: 10, 213 PubMed

Figueras M.J., and J. J. Borrego; (2010). New Perspectives in Monitoring Drinking Water Microbial Quality. Int. J. Environ. Res. Public Health: 4179-4202 PubMed

Fontes, M. C., M. J. Saavedra, A. Morena, C. Martins, and A. Martinez-Murcia; (2010). Phylogenetic identification of Aeromonas simiae from a pig, first isolate since species description. Vet. Microbiol.: 142, 313-316 PubMed

Collado, L.; Cleenwerck, I.; Van Trappen, S.; De Vos, P.; Figueras, M.J.; (2009). Arcobacter mytili sp. nov., an indoxyl acetatehydrolysis-negative bacterium isolated from mussels. Internat. J. System. Evolution. Microbiol.: 56 6, 1391-1396PubMed

Figueras, M.J.; Alperi, A.; Saavedra, M.J.; Ko, W.-C.; Gonzalo, N.; Navarro, M.; Martínez-Murcia A.J.; (2009). Clinical Relevance of the Recently Described Species Aerononas aquariorum. J. Clin. Microbiol.: 47 11, 3742-3746 PubMed

Plutzer, J.; Karanis, P.; (2009). Genetic polymorphism in Cryptosporidium species: An update. Vet. Parasitol.: G Model Vetpar:165 3-4, 187-199 PubMed

Harth-Chu, E.; Espejo, R.T.; Christen, R.; Guzmán, C.A; Höfle M.G.; (2009). Multiple-Locus Variable-Number Tandem-Repeat Analysis for Clonal Identification of Vibrio parahaemolyticus Isolates by Using Capillary Electrophoresis. Appl. Environ. Microbiol.: 75 12, 4079-4088 PubMed

Bouzid, M.; Heavens, D.; Elwin, K.; Chalmers, R.M.; Hadfield, S.; Hunter, P.R.; Tyler, K.M.; (2009). Whole genome amplification (WGA) for archiving and genotyping of clinical isolates of Cryptosporidium species. Parasitology: 137 1, 27-36 PubMed

Demartaa, A.; Kupfera, M.; Riegelb, P.; Harf-Monteilb, C.; Tonollaa, M.; Peduzzia, R.; Monerac, A.; Saavedra, M.J.; Martinez-Murcia, A.;(2008). Aeromonas tecta sp. nov., isolated from clinical and environmental sources. Systematic and Applied Microbiology: 314, 278-286 PubMed

Plutzer, J., Karanis, P., Domokos, K., Törökné, A., Márialigeti, K.; (2008). Detection and characterization of Giardia and Cryptosporidium in Hungarian raw, surface and sewage water samples by IFT, PCR and sequence analysis of the SSUrRNA and GDH genes. Int. J. Hyg. Env. Health: 211 5-6, 524-533 PubMed

Bouzid,M.; Steverding,D.; Tyler,K.M.; (2008). Detection and surveillance of waterborne protozoan parasites. Curr. Op. Biotech.:19 3, 302-306 PubMed

Christen, R.; (2008). Global sequencing: a review of current molecular data and new methods available to assess microbial diversity. 23 4, 253-268 PubMed

Christen, R.; (2008). Identification of pathogens – a bioinformatic point of view. Curr. Op. Biotech.: 19, 266-273 PubMed

Brettar, I.; Höfle, M.G.; (2008). Molecular assessment of bacterial pathogens – a contribution to drinking water safety.. Curr. Op. Biotech.: 19 3, 274-280 PubMed

Bosch,A.; Guix,S.; Sano,D.; Pinto,R.M.; (2008). New tools for the study and direct surveillance of viral pathogens in water.Curr. Op. Biotech.: 19 3, 295-301 PubMed

Croce O.; Chevenet, F.; Christen, R.; (2008). OligoHeatMap (OHM): an online tool to estimate and display hybridizations of oligonucleotides onto DNA sequences. Nucl. Acids Res.: 36, 154-156 PubMed

Martinez-Murcia,A.J.; Monera,A.; Alperi,A.; FiguerasM.J.; Saavedra,M.J.; (2008). Phylogenetic evidence suggests that strains of Aeromonas hydrophila subsp. dhakensis belong to the species Aeromonas aquariorum sp. nov.. Curr. Microbiol.: 58 1,76-80 PubMed

Henne,K.; Kahlisch,L.; Draheim,J.; Brettar,I.; Höfle,M.; (2008). Polyvalent fingerprint based molecular surveillance methods for drinking water supply systems.. Water Science and Technology: Water Supply: 8 5, 527-532

Leader

Groups

There are no results

Coordinator

Helmholtz Centre for Infection Research (DE)

Funding agency

EU-Projects

TARPOL

Targeting environmental pollution with engineered microbial systems à la carte

Synthetic Biology deals with the rational combination of biological properties with central elements of engineering design. We argue that by merging the genetic tool box already available with disciplines such as electrical, mechanical, or chemical engineering and computer sciences, there is an extraordinary opportunity to take a fresh approach to longstanding environmental pollution problems through a vigorous application of modelling techniques and organizing the development of novel biological (e.g. catalytic) systems along a hierarchical architecture with defined and standardized interfaces. However, this endeavour faces 3 major bottlenecks that this Coordination Action attempts to overcome: [i] The scientific and technical communities of european contributors to the application of SB to environmental issues (i.e., Environmental Biotechnologists, Bioinformaticians and experts on the Origin-of-Life subject) have so far failed to recognise their latent capacity to shape a fresh discipline at their very interface, [ii] The new field still misses a comprehensive language and a shared conceptual frame for description of minimally functional biological parts (specifically dealing with catalytic properties and regulatory circuits) and [iii] The development of the SB field touches upon social sensitivities related to recreating life-in-the-test-tube, which threats with a re-enactment of the controversy on GMOs and thus it worries off the needed industrial ease in the field. To tackle all these challenges, TARPOL proposes a dynamic 2-year programme of activities, run by a large collection of stakeholders in the field and aimed at coordinating the so far fragmented efforts to direct this emerging discipline into the most industrially beneficial and socially viable directions.

Speaker

Vitor Martins dos Santos

Coordinator

Universitat de Valencia (ES)

Funding agency

EU-Projects

FLUINHIBIT

Small Molecule Inhibitors of the Trimeric Influenza Virus Polymerase

FLUINHIBIT aims at discovering small molecule inhibitors of the influenza virus A subunit interaction between PA and PB1, crucial for viral replication.Starting from an inhibitory peptide, and supported by characterization of the PB1-binding domain of PA, molecular modeling will be employed to rationally design and synthesize peptidomimetics via traditional medicinal chemistry and a novel fragment based library synthesis approach. In parallel, a high-throughput assay will be developed to screen large compound collections and unique in-house small molecule libraries. The resulting hits will be profiled in cell-based assays and lead candidates with antiviral activity will be identified for preclinical development.

Partners

 

Biotechnology companies

PiKe Pharma GmbH, Switzerland

Inte:Ligand GmbH, Austria

Academic institutions

University Hospital Freiburg, Freiburg, Germany

Institute of Biotechnology, Vilnius, Lithuania

Helmholtz Centre for Infection Research, Braunschweig, Germany

University of Siena, Siena, Italy

Speaker

Ronald Frank

Coordinator

PiKe Pharma GmbH (CH)

Funding agency

EU-Projects

FASTEST-TB

Development and Clinical Evaluation of Fast Tests for Tuberculosis Diagnosis

It is widely accepted that rapid, cost-effective diagnosis of high sensitivity and specificity is a pre-requisite for the prevention and control of tuberculosis, a global disease in humans killing more than 3 million people annually. Methods and devices currently in use do not meet these requirements. The main objectives of this proposal are 1. to identify novel antigens using genomic and proteomic approach, 2. to purify sufficient quantities of antigens and raise antibodies  3. optimise immobilisation conditions for the specific antigens and antibodies on different carriers, 3. manufacture and evaluate the tests using approximately 6000 clinical specimens (sputum, saliva, serum, urine) from TB patients before and during therapy. In our opinion, such tests and  devices would be a major breakthrough in the early diagnosis and prevention of tuberculosis. In this project, experts from EU member states and  scientists from TB-endemic countries (India, Turkey, Nigeria) shall evaluate the clinical potential of antigen and antibody detection  using the  high speed, cost-effective POC tests, with which  results can be obtained  on site within 20 min. The main  aim is to develop  a non-invasive, low cost test stable at room temperature enabling its application in developing countries. 

 

Speaker

Helmut Blöcker

Coordinator

LIONEX Diagnostics & Therapeutics GmbH (DE)

Funding agency

EU-Projects

EMERGENCE

Setting the bases for synthetic biology in Europe

Synthetic biology has emerged as a very recent but highly promising approach to re-organizing the scientific biological endeavor by integrating central elements of engineering design. By applying the tool box of engineering disciplines such as electrical, mechanical, or chemical engineering and computer sciences, including the vigorous application of modeling techniques and organizing the development of novel biological systems along a hierarchical systems architecture with defined and standardized interfaces, synthetic biology aims at no less than revolutionizing the way we do bioengineering today. If successful, synthetic biology will transform bioengineering into a highly successful and sustainable life science industry.The objective of this coordination action (CA) EMERGENCE is to provide a communication and working platform for the emerging European synthetic biology community in order to strengthen the organizational and conceptual basis of the synthetic biology as a true engineering discipline in biological engineering.

Partners

 

Federal Institute of Technology (ETH Zurich), Sven Panke, Jörg Stelling, Frauke Greve

Consejo Superior de Investigaciones Scientificas (CSIC), Victor de Lorenzo

Spanish National Cancer Research Centre (CNIO), Alfonso Valencia

Helmholtz Zentrum für Infektionsforschung, (HZI), Vitor Martins dos Santos

Royal DSM, Luis Pasamontes

University College London (UCL), Nicolas Szita

Geneart AG, Ralf Wagner, Marcus Graf

Center for Genomic Regulation (CRG), Luis Serrano

University of Cambridge (UCAM), Jim Haseloff

Ecole Polytechnique (EP), Alfonso Jaramillo

Massachusetts Institute of Technology (MIT), Randy Rettberg

Speaker

Vitor Martins dos Santos

Coordinator

ETH Zürich (CH)

Funding agency

EU-Projects

CASIMIR

Coordination and Sustainability of International Mouse Informatics Resources

Casimir logo 200CASIMIR is a coordination action of the 6th Framework Programme of the European Commission, which focuses on co-ordination and integration of databases set up in support of FP5 and FP6 projects containing experimental data, including sequences, and material resources such as biological collections, relevant to the use of the mouse as a model organism for human disease. Interoperability of disseminated databases will provide enormous synergy in the provision, integration and analysis of a wide range of data with concomitant added value for research projects. Having set standards and benchmarks the proposed action will then reach out to co-ordinate other European and International databases and consult with the Community.

The project comprises eight work packages and eight partners.

WP8 - User interactions

Prof. Dr. Klaus Schughart

Objectives

Identify and describe use cases for database queries, analysis and representation of results through:

  • Holding user group meetings
  • Generate use reports
  • Assessment of scientific and financial value of current and future databases to users
  • Collate and report on community feedback from Web publications, literature publications and illustrative study.

Funding

European Commission within its FP6 Programme, under the thematic area "Life sciences, genomics and biotechnology for health".

Contract number: LSHG-CT-2006-037811. 

Partners

 

University of Cambridge, Cambridge

MRC- Medical Research Council, Oxfordshire Medical Research Council, Human Genetics Unit, Edinburgh

Helmholtz Zentrum Braunschweig - German Research Centre for Infection Research

Helmholtz Zentrum Muenchen - German Research Center for Environmental Health

European Molecular Biology Laboratory (EMBL), Monterotondo, Rome

European Bioinformatics Institute, Hinxton, Cambridge

FLEMING-Biomedical Sciences Research Center

Alexander Fleming Institute of Immunology Institute of Immunology, BSRC Alexander Fleming, Athens

CNR-Consiglio Nazionale delle Ricerche-Istituto di Biologia Cellulare (CNR-IBC) Monterotondo Scalo, Rome (Italy)

Istituto di Biologia Cellulare, CNR, Campus "A. Buzzati-Traverso", Rome

Leader

Groups

Speaker

Klaus Schughart

Coordinator

Prof. Dr. Paul Schofield, Cambridge University (UK)

Funding agency

EU-Projects

ProteomeBinders

A Eurropean Infrastructure of Ligand Binding Molecules against the Human Proteome

ProteomeBinders is a European consortium proposing to establish a comprehensive infrastructure resource of binding molecules for detection of the human proteome, together with tools for their use and applications in studying proteome function and organisation.
This 4-year FP6 Research Infrastructures Coordination Action, started in March 2006, is funded with 1.8 M€ and links 25 EU and 2 USA partners, leaders in the area of binders and their applications. The project is coordinated by Dr Mike Taussig (Cambridge). We advocate the organisation of an infrastructure of binders, available at cost and with no restrictions for research use, for which we are applying for funding under FP7.
Currently there is no pan-European platform for the systematic development and quality control for these essential reagents. We aim to provide a set of consistently characterised binders, required to detect all the relevant human proteins in tissues and fluids in health and disease. As the size of the human proteome is at least an order of magnitude greater than the ~ 21.000 protein coding genes known to date, and as for many applications several binders against each target are needed, the scale of our project is potentially immense.
To date, antibodies are the most widely used protein-binders, but novel binder types based on alternative protein scaffolds, nucleic acids, peptides and chemical entities each have significant advantages and will be carefully evaluated. We will coordinate a European resource by integrating existing infrastructures, reviewing technologies and high-throughput production methods, standardising tools and applications, and establishing a database.
Being one of the largest genome-scale projects in Europe, aiming ultimately to produce and collect hundreds of thousands of specific binders, the ProteomeBinders resource will bring huge benefits for basic and applied research, impacting on healthcare, diagnostics, target discovery for drug intervention and therapeutics.

Partners

 

Department of Immunotechnology, Lund University, Sweden
Create Health - Strategic Centre for Clinical Cancer Research

Biosciences Division, Los Alamos National Laboratory, USA

University College, Dublin, Ireland

CNRS-Universités Aix-Marseille I & II, France

Department of Biotechnology, Technical University Braunschweig, Germany
Antibody Factory

Department of Chemical Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany
ChemBioNet

Structural and Computational Biology Unit, EMBL, Heidelberg, Germany
ELM: Functional sites in proteins
phosphoELM: S/T/Y phosphorylation sites

SomaLogic Inc., Boulder CO, USA

Department of Biochemistry, University of Kassel, Germany

Proteomics Services, European Bioinformatics Institute, Hinxton, UK
HUPO-PSI: Proteomics Standards Initiative

Division of Functional Genome Analysis, German Cancer Research Center, Heidelberg, Germany

NMI, Tübingen, Germany

VTT Technical Research Centre of Finland, Turku, Finland

In-vitro ligand screening group, Max Planck Institute of Molecular Genetics, Berlin, Germany
Antibody Factory

Genomics & Proteomics Core Facilities, German Cancer Research Center, Heidelberg, Germany

Advanced Molecular Techniques in Genetics, Proteomics, and Medicine, The Rudbeck Laboratory, Uppsala University, Sweden
MolTools - developing tools for the postgenomic era

Center for Human and Clinical Genetics at the Leiden University Medical Center, Leiden, The Netherlands

imaGenes, Berlin, Germany

Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK

Dept. of Molecular and Cellular Interactions, VIB, Vrije Universiteit Brussel, Brussels, Belgium

School of Biotechnology, KTH, Stockholm, Sweden

Department of Biochemistry, University of Zurich, Switzerland

Medical Faculty University of Rijeka, Croatia

Laboratory of Analytical Chemistry and Biopolymer Structure Analysis, University of Konstanz, Germany

EMBL Monoclonal Antibody Core Facility, Monterotondo, Italy

Laboratoire Bordelais de Recherche en Informatique, Bordeaux, France
ProteomeBinders Bioinformatics Wiki

Biologische Chemie, Technische Universitaet Muenchen, Germany

Protein Technology Group,
Babraham Bioscience Technologies, Cambridge, UK
ESF Programme on Integrated Approaches for Functional Genomics
MolTools - developing tools for the postgenomic era

GSF - National Research Center for Environment and Health, Munich, Germany
Partner in Interaction Proteome (EU FP6 IP)

School of Biotechnology, KTH, Stockholm, Sweden
Human Protein Atlas: expression and localisation of proteins in human normal and cancer tissues



 

 



 

Speaker

Ronald Frank/Jutta Eichler

Coordinator

Babraham Bioscience Technologies Ltd (UK)

Funding agency

EU-Projects

EuroPathoGenomics EPG

European Virtual Institute for Functional Genomics of Bacterial Pathogens

EPG is a network of excellence (NoE "EPG") for functional genomics of bacterial pathogens. It is a consortium of leading European research teams committed to working with each other and with others to establish the European research area as an area of excellence in research on infectious diseases caused by bacterial pathogens.
The major objective is to organise the mass of genomic information that has become available, regarding both microorganisms and their hosts, into schemes allowing one to decipher the cross talks between pathogens and commensals and their host cell and tissue targets. Importantly, the critical mass established attracts the interest and collaboration of leading laboratories in other related basic disciplines, heightening the potential for incisive multi-disciplinary accomplishments. Based on this strong research background, high level teaching is organised at both graduate and postdoctoral levels, both in national institutions, capitalising on the current "cutting edge" research, and in European courses and workshops that also attract scientists from non-EU countries. Exchange programmes are designed to facilitate international and multidisciplinary development.

Partners

 

Bayerische Julius-Maximilians-Universität Würzburg

Helmholtz Zentrum für Infektionsforschung

Max-Planck-Institut für Infektionsbiologie

Institut Pasteur

Centre National de la Recherche Scientifique

University of Oxford

Imperial College of Science Technology and Medicine

Università di Padova

Università degli Studi di Messina

Università degli Studi di Siena

Consejo Superior de Investigaciones Cientificas

Universidad Pública de Navarra

Umeå Universitet

Karolinska Institutet

Uppsala Universitet

Lunds Universitet

Helsingin yliopisto

Danmarks Tekniske Universitet

Aarhus Universitet

Academisch Medisch Centrum bij de Universiteit van Amsterdam

Medizinische Universität Innsbruck

Veterinary Medical Research Institute of the Hungarian Academy of Sciences

University of Pécs

Institute of Microbiology of the Academy of Sciences of the Czech Republic

Tel Aviv University

Université René Descartes - Paris 5

Eberhard-Karls-Universität Tübingen

Technische Universität Kaiserslautern

Medizinische Hochschule Hannover

Universitätsklinikum Münster

Ludwig Maximilians Universität München

Ernst Moritz Arndt Universität Greifswald

Justus-Liebig-Universität Gießen

Université de la Mediterranée Aix-Marseille 2

BioMedTec Franken e.V.

SCIENION AG

Loke Diagnostics ApS

QIAGEN Hamburg GmbH

 








Speaker

Jürgen Wehland

Coordinator

Bayerische Julius-Maximilians-Universität Würzburg (DE)

Funding agency

EU-Projects

MUGEN

Integrated Functional Genomics in Mutant Mouse Models as Tools to Investigate the Complexity of Human Immunological Disease

MUGEN aims to structure and shape a world-class network of European scientific and technological excellence in the field of 'murine models of human immunological disease', to advance understanding of the genetic basis of disease and to enhance innovation and translatability of research efforts.
MUGEN's specific mission is to bring together different expertise from academic and industrial laboratories in order to study human immunological disease by integrating the participant's strengths in immunological knowledge with new approaches in functional genomics. In this way MUGEN expects to bring Europe a competitive advantage in the development of new diagnostic and therapeutic tools. In concert, MUGEN promotes training of young researchers and exploitation, dissemination and communication of scientific and technological excellence both within and outside of the network, to include all interested stakeholders in the area of human immunological diseases.

Partners

 

Biomedical Sciences Research Center “Al. Fleming” (FLEMING)
Inserm EMI -0101- Institut Pasteur (IP)
Deutsches Krebsforschungszentrum (DKFZ)
Centre d’ Immunology de Marseille – Luminy (CNRS)
University of Milano – Bicocca (UNIMIB)
Inst. Of Experimental Immunology, University of Zurich (EXPIMMZH)
Helmholtz-Zentrum for Infektionsforschung 
The Netherlands Cancer Institute (NKI-AVL)
EMBL (EMBL+EBI)
Medical Research Council (MRC-HIU+NIMR)

Speaker

Werner Müller

Coordinator

Biomedical Science Research Center (GR)

Funding agency

EU-Projects

SFB 566

Cytokine Receptors and Cytokine-Dependent Signal Paths as Therapeutic Target Structures

The collaborative research centre has put the main emphasis on identifying cytokine receptors and cytokine receptor-dependent intracellular signalling molecules as a target for the therapeutical influence of cytokines. The scientific program includes projects on one of the most exiting areas within cytokine research. The short- and medium-term aims include the identification of receptor molecules and signalling peptides as targets for both, positive or negative therapeutic influences of cytokine effects by either natural peptides or chemically produced specific inhibitors. In the long-term the clinical use of the identified inhibitors or stimulators of hematopoiesis is planned in different disorders of e.g. hematopoiesis, malignancies, immunology and defense of infections. As an example for a promising outcome of this therapeutic strategy the successful inhibition of the abl-specific tyrosine kinases in vivo in patients with Philadelphia-chromosome positive CML could be mentioned.

Partners

 

Medizinische Hochschule Hannover

Helmholtz Zentrum für Infektionsforschung

Groups

There are no results

Speaker

Prof. Dr. med. Karl Welte (MHH)

Funding agency

DFG - German Research Foundation

SFB 578

Development of Biotechnological Processes by Integrating Genetic and Engineering Methods – From Gene to Product

The Collaborative Research Center SFB 578 "Development of Biotechnological Processes by Integrating Genetic and Engineering Methods – From Gene to Product –", aims at combining and integrating methods available both from the basic sciences and the fundamental engineering sciences, notably genetics and biochemical engineering, to obtain high value-added products. The work primarily concerns processes for the microbial production of new heterologous proteins by recombinant production strains. The bacteria Escherichia coli (gram-negative) and Bacillus megaterium (gram-positive) as well as the mycelium-forming fungus Aspergillus niger are used as host organisms. The products under study are either pharmaceutically active (antibodies, bone morphogenetic proteins) or serve as biocatalysts to synthesize new oligosaccharides.

Partners

 

Institut für Pharmazeutische Technologie, TU Braunschweig

Institut für Mikrotechnik, TU Braunschweig

Institut für Mikrobiologie, TU Braunschweig

Institut für Biochemie und Biotechnologie, TU Braunschweig

Institut für Partikeltechnik, TU Braunschweig

Helmholtz Zentrum für Infektionsforschung GmbH, Abt. Strukturbiologie

Institut für Bioverfahrenstechnik, TU Braunschweig

Helmholtz Zentrum für Infektionsforschung GmbH, Zelluläre Proteomforschung

Institut für Elektrische Messtechnik und Grundlagen der Elektrotechnik, TU Braunschweig

Institut für Technische Chemie, TU Braunschweig

Institut für Organische Chemie, Würzburg

Institut für Verfahrenstechnik, Otto-von-Guericke-Universität Magdeburg

Groups

Speaker

Prof. Dr. Dieter Jahn

Funding agency

DFG - German Research Foundation

SFB 587

Immunreactions of the Lung in Infection and Allergies

In section A the projects are focused on the molecular interactions between microbes (bacteria, viruses and fungi) and the cells of the trachea, bronchi and lung. The role of the fusion protein of the respiratory syncytial virus interacting with epithelial cells of the respiratory tract is being studied. In another project the glycoprotein of influenza virus C will be used for gene transfer in differentiated epithelial cells. Three bacteria are used as tools in other studies: the expression of genes of Actinobacillus pleuropneumonia in the different phases of infection, virulence factors of Streptococcus suis in respect to the bacterium-host interaction and the relevance of the molecular mechanisms of the adherence of Streptococcus pneumoniae for mucosal or systemic vaccination strategies. The lung pathogen fungus Aspergillus fumigatus and its interactions with immune cells of the respiratory tract are being studied in the final project.
In section B the main aim is the investigation of the role of different cells of the immune system (lymphocytes, dendritic cells and eosinophilic granulocytes) in different infections and allergic disease models as well as in humans. The role of chemokine and neurotrophin receptors in allergy and inflammation of the lung is focused on in further projects. In volunteers and patients the interaction of environmental toxic agents with allergic reactions of the lung as well as the surfactant system of the lung will be studied by using different, well-controlled inhalation systems.

Partners

 

Helmholtz Zentrum für Infektionsforschung

Fraunhofer ITEM

Stiftung Tierärtzliche Hochschule Hannover

Twincore

Groups

Speaker

Prof. Dr. Gesine Hansen (MHH)

Funding agency

DFG - German Research Foundation

SFB 599

Sustainable bioresorbable and permanent implants of metallic and ceramic materials.

The Collaborative Research Centre (CRC) 599, “Sustainable bioresorbable and permanent implants of metallic and ceramic materials”, is an initiative of the Leibniz University of Hannover in conjunction with the Medical University of Hannover (MHH) and Hannover School of Veterinary Medicine (TiHo). The CRC is administratively run from the Centre of Biomedical Engineering (zbm), an institute within the Faculty of Mechanical Engineering at the Leibnitz University of Hannover. The spokesman of this technology-heavy CRC, Professor Thomas Lenarz, is from the medical field, which immediately makes clear the interdisciplinary focus of this project.

CRC 599 (also titled “Biomedical Technology” for short) is dedicated to fundamental research aimed at developing improved implants in order to benefit patients and reduce costs. The goal is - through innovations in materials, production and processing, and in the functionalisation, simulation, optimisation and testing of implants and their electrochemistry in interaction with biological materials - to maximize physicochemical and mechanical biofunctionality. Materials science-related approaches (drawn from the engineering and natural sciences) to temporary and permanent implants are to be tested both in vitro (in the test tube) and in vivo (in the living organism), characterised in terms of the underlying cell biology and represented using technical and medical simulation models. To ensure biocompatibility, the nature and composition of the material and the implant surface will be modified and adjusted using new methods.

The problem-solving approaches adopted by the Collaborative Research Centre for Biomedical Technology should answer not only unresolved questions in medicine; the new knowledge will also shed light on aspects of the engineering and natural sciences. Furthermore, this CRC will, on a lasting basis, deepen the collaboration between the specialist disciplines involved and provide promising young scientists with a unique opportunity to experience interdisciplinary work.

As a multidisciplinary initiative, this CRC is unique in Germany in terms of the interdependence that exists between materials sciences, human and animal medicine, with cell biology also fully integrated. To create a reliable basis for forward-looking science across a broad spectrum – and, in this project, this applies to the complex state of affairs with regard to use of implant material – it is necessary to promote very close networking and cooperation between disciplines, as is the case here. Because of this situation it is necessary (more so than for other CRCs) to provide parallel assistance to scientists from different fields, such as a physician and a natural scientist, within a single subproject. This will result in the project aims being pursued particularly effectively, and in close alliance between the various subject areas.

Partners

 

Medizinische Hochschule Hannover

Gottfried Wilhelm Leibniz Universität Hannover

Tierärztliche Hochschule Hannover

Laser Zentrum Hannover e.V.

Helmholtz-Zentrum für Infektionsforschung GmbH

Technische Universität Baunschweig

 

 



Groups

There are no results

Speaker

Prof. Dr. Thomas Lenarz (MHH-HNO)

Funding agency

DFG - German Research Foundation

SFB 621

Pathobiology of the Intestinal Mucosa

The intestinal mucosa is the largest exposed surface of the macro-organism. It is the interface of the intestinal organ system and is a sensitive seismograph for external (infectious) and internal (immunological) disturbances to which it is exposed and which can seriously impair its physiological functions (uptake and excretion). Of these unresolved questions and problems, three major areas of research are initiated at the Hannover Medical School (Medizinische Hochschule Hannover), the School of Veterinary Medicine Hannover (Tierärztliche Hochschule) and German Research Centre for Biotechnology (Gesellschaft für Biotechnologische Forschung) in Braunschweig.
There is still much unknown about postnatal interference and adaptation of the normal bacterial flora to the innate immune system at the border layer of the intestinal mucosa and the ensuing, normally lifelong peaceful coexistence in which micro- and macro-organism show mutual respect. The collaborative research centre intends to focus on the E. coli strain Nissle 1917 as the central probiotic agent in various individual projects and animal models, to manipulate this strain genetically and to determine the complete genome sequence in order to explain its probiotic effects. Another interdisciplinary theme closely involved in the probiotic approach is the Gnotobiotic Central Project Z1. The use of gnotobiotic and subsequently intentionally infected knock-out mouse strains will be of great importance for the analysis of the influence of the intestinal flora on the development, perpetuation and therapy of IBD.

Partners

 

Medizinische Hochschule Hannover

Stiftung Tierärztliche Hochschule Hannover

Helmholtz Zentrum für Infektionsforschung

Groups

Speaker

Prof. Dr. Reinhold Förster (MHH)

Funding agency

DFG - German Research Foundation

SFB 738

Optimisation of Conventional and Innovative Transplants

In the past years survival of transplanted cells and organs had been considerably improved by technical advances, new and better immunosuppressants and by improved anti-infectious therapies. Therefore, the scope of basic science and clinical therapies in transplantation medicine has also shifted: The overall goal being the induction of tissue-specific tolerance with the preservation of the general immunocompetence against infection (including CMV infection) and tumour development. In solid organ transplantation chronic graft dysfunction represents a major problem. This is not just mediated by immunological mechanisms, but is also due to infection, recurrence of pre-transplant disease and mesenchymal remodelling. In hematopoetic stem cell transplantation the main goal is the improvement of graft versus leukaemia reaction without causing graft versus host disease.
Because of the lack of donor organs and because of enhanced possibilities in molecular biology, transplantation research is also focussing on new cellular therapies, conditioned transplants and gene modifications. The Collaborative Research Centre tries to solve some of these problems. It consists of the following three projects areas:
(1) immunity and tolerance after hematopoetic stem cell transplantation,
(2) determinants of long-term survival of solid organ transplantation,
(3) new concepts of cellular and molecular transplantation medicine.
The three project areas are showing a close scientific and methodological collaboration. They are following the synergistic goal of improving the long-term transplant function and to develop new therapies. The conversion of research results into clinical medicine is facilitated by the fact that many members of the Collaborative Research Centre are active in the clinical transplant programmes of the Medizinische Hochschule Hannover. The research programme is investigating various aspects of immune function and induction of tolerance in animal models and in clinical samples.

Partners

 

Medizinische Hochschule Hannover

Groups

Speaker

Prof. Dr. Michael Peter Manns (MHH)

Funding agency

DFG - German Research Foundation

SFB 854

Molecular Organisation of Cellular Communication in the Immune System

Inter- and intracellular communication is necessary for the appropriate function of the immune system. During the defence against pathogens, cells of the innate and adaptive immune system (granulocytes, macrophages, mesangial cells, dendritic cells, T cells, B cells and epithelial cells) communicate with each other to prevent the expansion and spreading of microbes such as bacteria, viruses or fungi. Alterations of cellular communication can also lead to immunological disorders, for example immunodeficiency, autoimmune disease or allergy. Further, alterations of immune function also affect the ability of the immune system to detect and to eliminate malignant transformed cells.

Partners

 

Leibniz-Institut für Neurobiologie, Magdeburg

Freie Universität Berlin

Medizinische Fakultät, Universitätsklinikum Magdeburg A. ö. R.

Otto von Guericke Universität, Magdeburg

Helmholtz Zentrum für Infektionsforschung

Leader

Groups

Speaker

Professor Dr. Burkhart Schraven (Otto-von-Guericke-University Magdeburg)

Funding agency

DFG - German Research Foundation

CRC900

Chronic Infections: Microbial Persistence and how to control it

From an early age, people are colonized by numerous microorganisms, which develop mechanisms to stay present in different habitats in the human body over the entire lifespan of their host. The relationship between humans and persisting microorganisms can be of a symbiotic nature - for example, when the intestinal bacterial flora is involved in metabolic processes or when colonizing bacteria and Viruses affect the maturation of the immune system.

On the other hand, the colonization of the host by persistent microorganisms can just as well lead to disease and fatality, if certain microbial properties trigger pathogenic processes or a stable coexistence with normally innocuous microbes can either not be established or take a pathogenic course in the course of life due to genetically induced or acquired weaknesses of the host

Worldwide, chronic infections caused by HIV, HCV, Mycobacterium tuberculosis or Helicobacter pylori are an important cause for potentially preventable diseases and death. Moreover, the progress of modern medicine in terms of organ replacement and the increasing lifespan of patients with genetic defects in their defence system result in rising numbers of iatrogenic immunosuppressive or otherwise immuno-compromised persons. Likewise, the significance of opportunistic infections is on the rise as well, many of which are caused by persistent pathogens that are largely harmless in immuno-competent individuals.

New therapeutic approaches 

Given the clinical problems caused by chronic infections, it will be necessary in the long term to identify new therapeutic approaches to improve the life expectancy and quality of life of many of our patients. We therefore wish to better understand the underlying mechanisms that are necessary for the establishment or maintenance of a chronic Infection.

18 subprojects

This long-term goal is the purpose of the special research area applied for here. The collaboration of 18 subprojects studying different examples of chronically persistent microorganisms is aimed at gaining a better understanding of

  • how chronic infectious pathogens become established in the infected Host ,
  • how they manage through permanent adaptation of their genome and modulation of the gene expression to persist in the infected Host in the long-term, and
  • what possibilities are available to them to evade the defence mechanisms of the host and/or which of these defence mechanisms are essential for the prevention or containment of an infection with these pathogens.

Partners

Deutsche Forschungsgemeinschaft
Medizinische Hochschule Hannover
Helmholtz Zentrum für Infektionsforschung
Twincore

Groups

Speaker

Professor Dr. Thomas F. Schulz (MHH)

Funding agency

DFG - German Research Foundation

SFB 51 - Roseobacter

Ecology, Physiology and Molecular Biology of the Roseobacter clade: Towards a Systems Biology Understanding of a Globally Important Clade of Marine Bacteria

The Roseobacter clade is a major lineage of the family Rhodobacteraceae of Alphaproteobacteria. Its members form one of the most abundant and successful groups of non-obligately phototrophic prokaryotes in the marine environment. In contrast to the high ecological importance the knowledge of this clade and of its key players in the marine environment is still surprisingly limited. Consequently, in the framework of this proposed SFB/TR marine microbial ecologists, bacterial physiologists, biochemists, natural product chemists, geneticists and computer scientists from Braunschweig and Oldenburg join forces to investigate the Roseobacter clade from the ecosystem level down to systems biology of model organisms with respect to important metabolic processes.
 
The major goal is the understanding of evolutionary, genetic and physiological principles which constitute the secret of success for these bacteria. How is the genetic configuration of these bacteria successfully employed for rapid evolutionary adaptations to multiple habitats at the level of metabolic and related regulatory networks?

Partners

 

Carl von Ossietzky Universität Oldenburg

Technische Universität Braunschweig

Helmholtz Zentrum für Infektionsforschung

Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ)

Göttingen Genomics Laboratory

 

Groups

There are no results

Speaker

Professor Dr. Meinhard Simon (Carl von Ossietzky Universität Oldenburg)

Funding agency

DFG - German Research Foundation

TRR 77

Liver Cancer - From Molecular Pathogenesis to Targeted Therapies

Hepatocellular carcinoma (HCC) is one of the most frequent and dismal malignancies with so far limited therapeutic options but also an ideal model system for tumour research and the most relevant paradigm for virus-induced and inflammation-mediated cancer. Recent progress has demonstrated the feasibility of translating basic biomedical research findings into HCC therapy. The main aim of the SFB/TRR77 is to gain a profound understanding of the molecular basis of human hepatocarcinogenesis beginning with its initiation from chronic liver disease to its progression into metastatic cancer, its functional dissection and the identification of novel preventive, diagnostic, and therapeutic approaches.

Partners

 

Hannover Medical School

Heidelberg University Hospital

Speaker

Professor Dr. Peter Schirmacher (Universitätsklinikum Heidelberg)

Funding agency

DFG - German Research Foundation

SPP 1150

Signal Pathways to the Cytoskeleton and Bacterial Pathogenesis

The Priority Programme investigates the cytoskeleton as a "signal-responsive subcompartment" involved in various cellular processes, including signal transduction by extracellular stimuli and especially as a target of pathogen-host interactions. Dynamic changes of the cytoskeleton play pivotal roles in the interaction of microbial pathogens with their eukaryotic host cells and are prerequisites of infection biological processes (cellular microbiology). 
In the Priority Programme, cellular receptors, regulatory proteins and signal pathways are studied, which are involved in rapid, temporally and spatially regulated cytoskeleton changes. Dynamic protein-protein interactions of cytoskeleton components are investigated and structure-functions analyses of signaling molecules involved are studied. Of particular interest are signal proteins and molecular switches of the family of low-molecular-mass GTPases (e.g. Rho proteins) and their various effectors, including direct regulators of actin dynamics. Of interest are also signal pathways and regulatory proteins, which are involved inpathogen-host cell-interactions and which are modified and/or modulated by bacterial effectors and protein toxins. The experimental approach is multi- and interdisciplinary and covers methods from cell biology, microbiology and structural biology, including modern protein interaction analysis, protein structure analysis and genetic approaches. 
Aim of the Priority Programme is to define the precise pathways of signal/receptor-mediated changes in the cytoskeleton and to understand the dynamics of the cytoskeleton in pathogen-host interactions.

Partners

 

Ludwig-Maximilians-Universität München

Medizinische Fakultät, Universitätsklinikum Magdeburg A. ö. R.

Westfälische Wilhelms-Universität Münster

Medizinische Hochschule Hannover

Lehrstuhl Zellbiologie, Universität Konstanz

Universitätsklinikum Erlangen

Institut für Medizinische Strahlenkunde und Zellforschung
der Universität Würzburg

Leibniz-Institut für Neurobiologie Magdeburg

Helmholtz Zentrum für Infektionsforschung

 

Coordinator

Prof. Dr. Dr. Klaus Aktories (Albert-Ludwigs-Universität Freiburg)

Funding agency

DFG - German Research Foundation

SPP 1258

Sensory and regulatory RNAs in Prokaryotes

One of the most fascinating discoveries in recent biology has been the regulatory potential of regulatory RNAs. Recent estimates suggest that a typical microbial genome may encode hundreds of small regulatory RNAs. Such sRNAs are generally untranslated, and most often range from 50 to 250 nucleotides in length. Where characterised in detail, some sRNAs were found to regulate target genes by binding to (regulatory) proteins, whilst most of them turned out as antisense RNAs that act on trans-encoded mRNAs. Most bacterial mRNAs contain a 5'-untranslated region (5'-UTR) with more than the Shine-Dalgarno (SD) sequence required for interaction with the 30S ribosomal particle. Such extended 5'-UTRs can fold into complex structures with regulatory properties. RNA thermometers, for example, acquire a structure that blocks translation at low temperatures. Riboswitches control gene expression by ligand-induced conformational changes that control transcription termination, translation initiation or RNA processing. The goal of the Priority Programme is to bring together scientists to explore the regulatory potential of RNA in diverse prokaryotic systems. That is apart from the standard model bacteriaEscherichia coli and Bacillus subtilis, several other microbes including cyanobacteria, Rhizobiaceae, several pathogens and halophilic as well as methanogenic Archaea will be studied.

Partners

 

Deutsche Forschungsgemeinschaft

Leader

Groups

There are no results

Speaker

Professor Dr. Franz Narberhaus (Ruhr-Universität Bochum)

Coordinator

Professor Dr. Franz Narberhaus (Ruhr-Universität Bochum)

Funding agency

DFG - German Research Foundation

SPP 1316

Identification of host-adapted metabolic functions important for Yersinia pseudotuber­culosis virulence

Initial colonization of the gut and subsequent penetration of the intestinal epithelial layer by the enteric pathogen Yersinia pseudotuberculosis demands expression of a special set of early-stage virulence genes, whereas persistence and multiplication in subepithelial tissues and organs requires synthesis of other patho­genicity factors, e.g. the antiphagocytic Yop proteins. A complex network of transcriptional and post-transcriptional regulatory systems was identified to control expression of these virulence factors and important metabolic functions. In particular, the central carbon metabolism (glycolysis, TCA cycle) and associated amino acid and nucleoside catabolism were found to be co-regulated with expression of Yersinia virulence functions in response to temperature and nutrient availabi­lity. To gain a deeper insight into the host-adapted metabolism of Yersinia, the full spectrum of metabolic changes in response to the different virulence asso­ciated conditions (changes of temperature, nutrients, oxygen availability) will be elucidated using metabolome, fluxome, transcriptional and 13C-isotopologue profiling techniques. Additionally the molecular mechanisms mediating fine-tuned coregulation of metabolic and virulence genes over the course of the infection will be elucidated. Subsequently, expression and role of the identified host-adapted virulence pathways for patho­genesis will be evaluated in an established mouse infection model. Gained knowledge about crucial host-adapted metabolic pathways of an extracellular fast growing intestinal pathogen may lead to the identification of new targets for novel anti-infective compounds.

Partners

 

Deutsche Forschungsgemeinschaft

Leader

Groups

There are no results

Speaker

Professor Dr. Michael Hensel (Universität Osnabrück)

Funding agency

DFG - German Research Foundation

SPP 1394

Mast-cells - promoters of health and modulators of disease

Mast cells (MCs) have long been thought to be a dispensable cell type, which seemed only responsible for the annoying and sometimes even life threatening symptoms of allergic reactions. Over the last years it became evident, however, that MCs are also crucially important in optimal host defense against microbes, where they act as sentinels and effector cells of the innate immune responses. We and others have characterised the mechanisms by which MCs are activated, and identified how MC mediators contribute to the improved morbidity and mortality in bacterial infections. 
Here, the Priority Programme investigates potential signals leading to an optimisation of MC numbers and/or function in murine skin. To this end, we will employ extensive in vitro and in vivo analyses to identify and characterise signals, which may ultimately lead to an improved host response against bacterial skin infections. Furthermore, we will assess the efficacy and safety of such treatment in in vivo models of bacterial skin infections as well as models of allergic and autoimmune diseases and hypothesise that the selective and local enhancement of MC function will provide a prophylactic approach to reduce the risk of bacterial infections in individuals with high risks of infections.

Partners

 

Klinik für Dermatologie, Venerologie und Allergologie
Charité
– Universitätsmedizin Berlin

Universitäts-Hautklinik Eberhard-Karls-Universität, Tübingen

Deutsche Forschungsgemeinschaft

 

Leader

Groups

Coordinator

Prof. Dr. Marcus Maurer (Charité)

Funding agency

DFG - German Research Foundation

FOR 629

Molecular Mechanisms of Cell Motility

The central topic of the Research Unit is the interplay between molecular motors, the components of cell adhesion complexes, and the actin- and microtubule-based cytoskeleton. This complex interplay and its modulation by chemical and mechanical signals plays a key role in defining cell shape, motility, adhesion, and polarity. During embryogenesis, it is important for the organisation of three-dimensional cellular assemblies leading to the formation of tissues and organs. Increased motility contributes to invasion and metastasis of tumour cells. In recent years, considerable progress has been made in identifying the key players that drive a wide range of motile events and important details about the underlying molecular mechanisms have been revealed. However, information about the way in which actin filaments interact with microtubules and microtubules with focal adhesions is still scarce. 
While the details of the molecular mechanisms leading to the formation of cell surface extensions involving polarised actin-rich structures are beginning to emerge, it remains unclear why under certain conditions filopodia, lamellopodia or membrane ruffles are formed. It is crucial to understand the mechanical and biochemical signals that instruct the cytoskeleton to form a certain type of extension as the dynamic behaviour of polarised actin-rich structures is also responsible for the formation of specialised cell surface structures such as microvilli and stereocilia bundles. 
A better understanding of the molecular mechanisms of cell locomotion will contribute to our understanding of these physiological and pathological processes. We will work towards this goal using a multifaceted approach to characterise components of the actin- and microtubule-based cytoskeleton, adhesion complexes, and processive molecular motors. This will include the detailed biochemical and structural analysis of isolated proteins and protein complexes, the use of in vivo and in vitro assays to directly observe protein function, and molecular genetic approaches to selectively deplete proteins of interest or produce them in a recombinant form. Dictyostelium, tissue culture cells and mice will be used as model systems to study the function of proteins of interest. This allows the researchers to take advantage of the powerful molecular genetics, easily accessible phenotypes and strong biochemistry in Dictyostelium and to test the relevance of our findings in the context of more complex systems.

Partners

 

Medizinische Hochschule Hannover

Leader

Groups

Coordinator

Professor Dr. Dietmar J. Manstein (MHH)

Funding agency

DFG - German Research Foundation

FOR 1220

Prosthetic Groups: Transport and Insertion - PROTRAIN

Over one third of all proteins contains prosthetic groups, metals and cofactors. These groups are indispensable for catalysis as they form part of the catalytic centre of the enzyme or they are part of intramolecular electron transport. Prosthetic groups are of key importance for a large number of biological reactions, e.g. photosynthesis, energy metabolism, oxygen transport, anabolism and catabolism, redox reactions, cell signalling etc. While the biosynthesis of many prosthetic groups is well understood it is largely unknown how prosthetic groups are directed to various cellular destinations or stored after their synthesis, and how they ultimately find the way into their correct cognate proteins. Intricate mechanisms have to control distribution, trafficking and insertion into proteins as most of these prosthetic groups are extremely fragile and air-sensitive. 

Consequently, there must be a plethora of transporters, chelators, metal cofactors, protein folding chaperones, metallochaperones, carrier proteins, storage proteins and insertases involved. The finely tuned interplay of these components ensures the safe transport, even through membranes, the protection and insertion of prosthetic groups into their target proteins. This complex machinery is completely unexplored. It can be assumed that its level of complexity should equal that of the protein trafficking. 
Based on our long-standing background in biosynthesis und functionality of prosthetic groups, we focus in Braunschweig with seven projects on the investigation of the unknown molecular strategies for transport and insertion of molybdenum cofactors (Moco) and hemes into enzymes. In close cooperation, a broad spectrum of methods will be employed ranging from genetic, biochemical and structural approaches to chemical synthesis and bioinformatics tools. The main objective of the Research Unit is to fill the gap in our knowledge about (1) what happens with the prosthetic groups heme and Moco subsequent to their biosynthesis, and (2) how is the process of insertion of these groups into their cognate apo-enyzmes catalysed. 
We will dissect the single steps of these processes in order to generate a mechanistic understanding of the biochemical, biophysical and cellular processes governing these dynamic phenomena. We envisage the deduction of novel fundamental principles that will allow to understand and to predict these processes at the molecular level both in bacterial and eukaryotic systems.

Partners

 

Technische Universität Braunschweig

Groups

Coordinator

Professor Dr. Ralf R. Mendel (TU Braunschweig)

Funding agency

DFG - German Research Foundation

FOR 1406

Exploiting the Potential of Natural Compounds: Myxobacteria as Source for Leads, Tools, and Therapeutics in Cancer Research

Natural products play an important role in drug discovery and biomedical research for two major reasons: Firstly, they possess an enormous structural diversity serving as privileged scaffolds in drug discovery (leads) and secondly they have proven to be valuable tools for examining cellular processes and identifying targets in signal transduction pathways. However, besides this enormous potential of natural products, obstacles exist. These are mainly due to difficulties in isolation and/or synthesis in sufficient quantities and, consequently, to a lack of thorough investigations concerning their molecular mechanisms of action and their targets. Thus, the potential of natural products in pharmaceutical sciences is not yet fully exploited.
This Research Group (RG) will meet this challenge by exemplarily focusing on
natural products from myxobacteria: 1) novel species of myxobacteria will be
identified and screened for bioactive compounds. 2) innovative biotechnological/(bio)synthetic approaches will be used to guarantee compound supply as well as create analogs of them. 3) Innovative in silico approaches will help to define the mode of action of the natural compounds, and to design more potent analogs. 4) By combining chemistry with proteomics yet unknown targets of the natural compounds shall be identified. 5) Finally, with regard to anticancer pharmacology of the myxobacterial compounds the Research Group aims at attractive and promising avenues: We will not only focus on tumor death inducing effects of compounds, but also examine their influence on tumor cell migration as well as on cancer immunosurveillance and their underlying signaling pathways. Moreover, besides tumor cells, vascular cells and immune cells known to play a role in cancer survival are in the center of interest for respective pharmacological work. To this end complex cellular and in vivo systems as well as pharmacogenomics are employed for first line characterization of promising compounds instead of isolated target screening as
usually performed in industrial drug discovery.
Bringing together scientists with strong expertise in the field of biotechnology of
myxobacteria, pharmaceutical and natural product science, this Research Group will be a very important instrument for the support of “Drug Discovery from Nature”.

Partners

 

Helmholtz Institute for Pharmceutical Research (HIPS) Saarland

Saarland University

LMU Munich

Saarland University

ETH Zurich

TU Munich

University of Jena

 

 

Groups

Speaker

Professor Dr. Angelika Vollmar (LMU München)

Funding agency

DFG - German Research Foundation

KFO 250

Genetische und zelluläre Mechanismen von Autoimmunerkrankungen

Das Ziel der Klinischen Forschergruppe ist es, ausgehend von genetischen Studien in Familien mit gehäuften Autoimmunphänomenen und gut charakterisierten Patientenkohorten über innovative Tiermodelle und aktuellste immunologische und genetische Ansätze die zellulärenMechanismen systemischer und organspezifischerAutoimmunerkrankungen zu entschlüsseln.

Partners

 

Medizinische Hochschule Hannover

Groups

Speaker

Prof. Dr. Reinhold E. Schmidt (MHH)

Funding agency

DFG - German Research Foundation

Nanobiotec

Network for Research and Academic Training on Surface Biofunctionalization

Partners

 

Universidad Federal de Rio Grande do Sul, Porto Alegre, and various other universities in Brazil

Groups

There are no results

Funding agency

Other

Graduate Grant

Use of metabolites of Basidiomycotina fungi to modulate microbial biofilms

Groups

There are no results

Funding agency

DAAD - German Academic Exchange Service

Risc habitat megacities

Water, Health and Governance

Partners

 

UFZ Leipzig

FZK

DLR

GFZ

Groups

There are no results

Funding agency

Helmholtz

Graduate Grant of the Egypt Government

Diversity of microbial communities in biofilms growing on hexachlorohexane and related substrates

Groups

There are no results

Funding agency

Other

Thai–German Symposium

1st Thai–German Symposium on Regenerative Medicine

Partners

 

Hannover Medical School (MHH)

GKSS Berlin-Treptow

FZK

University of Leipzig

University of Ulm

University of Regensburg

Charité Berlin

 

Groups

There are no results

Funding agency

DFG - German Research Foundation

DFG Graduate School

Functional biodiversity of Pseudomonas species in biofilm communities degrading polycyclic aromatic hydrocarbons

Partners

 

Hannover Medical School (MHH)

Technical University Braunschweig

Technical University of Denmark, Lyngby

Rigshospitalet, Copenhagen

Groups

There are no results

Funding agency

DFG - German Research Foundation

Microbial diversity

Studies of uncultured marine microbial diversity using biomolecule signature analysis and metagenomic libraries

Partners

 

National Centre for Cell Science

Pune University Campus, India

Groups

There are no results

Funding agency

DAAD - German Academic Exchange Service

DFG Graduate School

Carbon sharing of Pseudomonas spp. in a 4-chlorosalicylate degrading community (Pseudomonas Course of Lecture 3)

Partners

 

Hannover Medical School (MHH)

Technical University Braunschweig

Technical University of Denmark, Lyngby

Rigshospitalet, Copenhagen

Groups

There are no results

Funding agency

DFG - German Research Foundation

Biodiversity

Biodiversity and secondary metabolites of sponge-associated bacteria

Partners


Museu de Ciencias Naturais, Porto Alegre, Brazil

Groups

There are no results

Funding agency

BMBF - Federal Ministry of Education and Research

Biodiversity

Biodiversity and metabolic activities of oligotrophic biofilms

Partners


Universidade de São Paulo, Piracicaba, Brazil

Groups

There are no results

Funding agency

BMBF - Federal Ministry of Education and Research

Microorganism

Detection of microorganism after the flood

Partners

 

UFZ

GKSS

Technologiezentrum Wasser (TZW) Dresden and Karlsruhe

Institute for Environment and Sustainability/ISPRA Joint Research Centre, Italy

Sächsische Akademie der Wissenschaften zu Leipzig

TU Bergakademie Freiberg, Institute for Mineralogy

University of Hamburg, Institute for Inorganic and Applied Chemistry, Institute for Organic Chemistry

Groups

There are no results

Funding agency

BMBF - Federal Ministry of Education and Research

Biodiversity

Assessment of the biodiversity of tropical fungi and their antibiotic activities

Partners


“Alejandro of Humboldt" Fundamental Research Institute for Tropical Agriculture (INIFAT), La Habana, Cuba

Groups

There are no results

Funding agency

BMBF - Federal Ministry of Education and Research

Soil functions

Organische Substanz und mikrobielle Diversität als Parameter der Steuerung wichtiger Bodenfunktionen

Groups

There are no results

Funding agency

Helmholtz

Diabetic foot infections

Metagenomics and host-pathogen interactomics in diabetic foot infections

The prevalence of diabetes mellitus worldwide has increased dramatically during the past few decades, and it is expected to increase even more in the future. As a result of the increase in diabetes, the comorbidities associated with the disease have also risen. Foot infections are the most common diabetes-related cause of hospitalization that very often results in amputation. The speed with which the DFI progresses, from a seemingly minor skin infection to a limb-threatening condition, reinforces the need for prompt diagnosis and treatment. Although generally, diagnosis is based on signs and symptoms of inflammation, accurate identification of infecting pathogens is paramount to reduce the spread of infection and decrease any unnecessary tissue loss. This is a complex task since diabetic foot infections (DFI) are usually polymicrobial and chronic infections may host biofilm bacteria not adequately detected by current microbiological testing. To deal with this complexity, a metagenomic approach will be used in this consortium to determine the impact of the microbial diversity and bioburden in the progression of DFI. This approach will be also used to evaluate the potential contribution of the skin microbiome to DIF. The most common and serious complication of DFI is osteomyelitis that can results in progressive inflammatory destruction of bones. Osteomyelitis is present in approximately 20% of cases of DFI and greatly increases the likelihood that the patient will require extremity amputation. Staphylococcus aureus is the most common cause of osteomyelitis in DFI patients. Diabetic foot osteomyelitis is often refractory to antibiotic treatment, a problem exacerbated by the increasing level of antibiotic-resistance among S. aureus clinical isolates as well as by the emergence of particularly persistent antibiotic-resistant clones during infection. Staphylococcal bone infections are thus likely to be a continuing and probably increasing problem in diabetic patients and an understanding of the interactions of this pathogen with bones is central to development of novel therapeutic strategies required to treat these increasingly antibiotic-resistant and persistent infections. To achieve a comprehensive understanding of the host-pathogen interactions during bone infection, it is also contemplated in this consortium to determine global host-pathogen transcriptome changes that occur during staphylococcal bone infection. The combine use of bacterial and host transcriptome to study the same infected tissue will reveal the dialogue between pathogen and host in a gene-by-gene and site- and time-specific manner. The final goal is to identify which bacterial transcripts influences host gene expression or vice versa (interactome). Overall, this consortium will provide valuable information that can be used to improve the diagnosis, prevention and treatment of DFI and its long-term complications.

Partners

 

Prof. Dr. Trinad Chakraborty, Institut für medizinische Mikrobiologie, Universitätsklinikum Gießen und Marburg

PD Dr. Rolf Daniel, Institut für Mikrobiologie und Genetik, Georg-August-Universität Göttingen

Prof. Dr. Eugen Domann, Institut für medizinische Mikrobiologie, Universitätsklinikum Gießen und Marburg

Groups

Coordinator

Dr. Eva Medina, Helmholtz Zentrum für Infektionsforschung, Braunschweig

Funding agency

BMBF - Federal Ministry of Education and Research

Mast cells

Phagocytosis-independent antimicrobial activity of mast cells by formation of extracellular traps: cellular receptors involved and underlying molecular mechanism

It has been increasingly recognized that mast cells are critical components of host defense against pathogens. We have recently described a completely novel mechanism used by mast cells to kill bacteria such as Streptococcus pyogenes or Staphylococcus aureus. This mechanism consists on entrapping them in extracellular structures similar to the extracellular traps described for neutrophils. The mast cells extracellular traps (MCETs) are composed of DNA, histones, tryptase, and the anti-microbial peptide LL-37. Formation of MCETs is not the result of passive release of DNA and granule proteins during cellular disintegration but rather an active and controlled process in response to specific stimulation and strongly dependent on the production of reactive oxygen radicals (ROS). This type of death has been recently termed "Etosis". Etosis is neither typical apoptosis nor necrosis and it is characterized by disintegration of the nuclear membrane concomitant with cytoplasmic granule dissolution, allowing the components of the traps to mix in the cytoplasm before been released.

The goals of this grant proposal are the characterization of the mast cell receptors and bacterial factors triggering the formation of MCETs as well as the characterization of the downstream molecular mechanisms, specifically how ROS trigger mast cell death.

This knowledge will further our understanding about the anti-microbial activity of mast cells and their contribution to host defense against infectious pathogens.

Groups

Coordinator

Dr. Oliver Goldmann Arbeitsgruppe Infektionsimmunologie Helmholtz Zentrum für Infektionsforschung

Funding agency

DFG - German Research Foundation

S. aureus

Identifizierung genetischer Faktoren und immunologischer Mechanismen welche der Resistenz oder Suszeptibilität gegenüber S. aureus in Mausmodellen zugrunde liegen

Partners

 

Universitätsklinikum Münster (UKM)

Universität Kiel

Universität Bonn

Universität Tübingen

Universität Homburg

Universität Giessen

Groups

Coordinator

Prof. Cord Sunderkötter (UKM)

Funding agency

BMBF - Federal Ministry of Education and Research

IG-SCID

Indo-German Science Center for Infectious Diseases - Gemeinsam gegen Infektionskrankheiten

Infektionskrankheiten sind ein weltweites Problem. Jährlich sind sie für mehr als ein Viertel aller Todesfälle verantwortlich. Dabei schienen sie in der Mitte des 20. Jahrhunderts besiegt. Vor mehr als 120 Jahren entdeckte Robert Koch die Erreger von Milzbrand, Tuberkulose und Cholera. Eine neue Ära der Erforschung von Krankheitserregern brach an. Mit ihr stiegen sowohl die Lebensqualität als auch die Lebenserwartung. Die Entdeckung von Antibiotika und die Entwicklung neuer Impfungen ließ Mediziner und Forscher glauben, der Mensch habe den Kampf gegen die Krankheitserreger gewonnen. Aber Mikroben und Viren gaben sich nicht geschlagen: Antibiotika-Resistenzen, neue Varianten von bekannten Erregern und bisher unbekannte Krankheiten sind heute eine große Herausforderung für die Menschheit. Vermeintlich kontrollierbare Krankheiten wie Tuberkulose breiten sich wieder aus. Neue Infektionskrankheiten wie AIDS, SARS oder BSE tauchen auf. Viele Krankheiten, die scheinbar nichts mit Bakterien, Viren oder Pilzen zu tun haben – darunter auch einige Krebsformen – lassen sich ursächlich auf Infektionen zurückführen. Spätestens seit dem Auftauchen der "Neuen Grippe" im April 2009 sind sich viele Menschen der konstanten Bedrohung durch Infektionskrankheiten bewusst. Dabei sind die Strategien von Mikroben und Viren,  uns zu  infizieren, nicht weniger ausgeklügelt als die Strategien des Menschen, diese Krankheitserreger zu bekämpfen.

Wir brauchen dringend neue Medikamente und Impfstoffe. In den Industrienationen sind Krankenhauskeime und multiresistente Bakterien wie Staphylococcus aureus ein großes Problem. Tuberkulose und Hepatitis-Infektionen hingegen spiegeln das soziale Gefüge in der Welt wieder: Sie treffen arme Menschen am stärksten. Helfende Medikamente sind für viele unerschwinglich. Günstige Alternativen fehlen häufig. Infektionskrankheiten kennen keine Ländergrenzen und so sind Kooperationen von Wissenschaftlern verschiedener Länder ein wichtiger Schlüssel beim erfolgreichen Kampf gegen Krankheitserreger.

Das "Indo-German Science Center for Infectious Diseases" – deutsch-indisches Wissenschaftszentrum für Infektionskrankheiten – ist ein solcher Zusammenschluss. Von indischer Seite koordinieren das "Indian Council of Medical Research" (ICMR) und die Jawaharlal-Nehru-Universität (JNU) das Projekt, auf deutscher Seite die Helmholtz-Gemeinschaft Deutscher Forschungszentren und das Helmholtz-Zentrum für Infektionsforschung (HZI) in Braunschweig sowie die MHH Hannover. Diese deutsch-indische Kooperation ist ein virtuelles Zentrum, aufgebaut auf den Ideen der indischen und deutschen Forscher, die in gemeinsamen Forschungsprojekten zusammenarbeiten. Zwischen den Forschern findet ein reger Informationsaustausch statt. Regelmäßige Besuche und gemeinsame Kongresse sichern den Wissenstransfer. Das Ziel des Zentrums ist es, gemeinsam Infektionskrankheiten zu erforschen, sie besser zu verstehen und mit diesem Wissen neue Medikamente und Impfstoffe zu entwickeln. Beide Länder wollen damit ihre Zusammenarbeit auf dem Gebiet der biomedizinischen Wissenschaft ausbauen und stärken.

 

Der Weg zum Zentrum

Die wissenschaftlich-technologische Zusammenarbeit zwischen Deutschland und Indien begann bereits 1971 mit einem Abkommen über die friedliche Nutzung der Kernenergie und des Weltraums und wurde  1974 um die Zusammenarbeit in wissenschaftlicher Forschung und technischer Entwicklung erweitert. 30 Jahre später, im November 2005, bekräftigten beide Länder diese Kooperation. Die Helmholtz-Gemeinschaft Deutscher Forschungszentren (HGF) strebte eine Internationalisierung auf dem Gebiet der Gesundheitsforschung an, und als Teil der HGF hat das Helmholtz-Zentrum für Infektionsforschung (HZI) in den vergangenen Jahren die Zusammenarbeit mit Indien konsequent ausgebaut. Eine bedeutende Rolle hierbei spielt Professor Gursharan Singh Chhatwal. Der gebürtige Inder ist Leiter der Abteilung "Medizinische Mikrobiologie" am HZI in Braunschweig und schlug die Brücke zwischen Indien und Deutschland. Sein Forschungsschwerpunkt sind Streptokokken-Infektionen. Professor Chhatwal ist sich der Bedeutung seiner Forschung bewusst: Während in Deutschland eine Infektion mit Streptokokken wie zum Beispiel bei Halsschmerzen oder Scharlach mithilfe von Penicillin gut behandelbar ist, sind dieselben Streptokokken in Ländern wie Indien ein ernstzunehmendes Problem. Nicht vollständig ausgeheilte Infektionen und unzureichende Antibiotikabehandlung führen dazu, dass sich die Streptokokken im Körper einnisten. Die Folge sind Erkrankungen wie die rheumatische Herzkrankheit bei Kindern. Zurzeit leiden etwa 15 Millionen Kinder im Alter zwischen fünf und 15 Jahren an dieser Krankheit. Eine halbe Million sterben pro Jahr.

Die offizielle Geburtsstunde des „Indo-German Science Center of Infectious Diseases“ (IG-SCID) war der 23. April 2006. Der Direktor des ICMR, Professor Nirmal K. Ganguly, und der Präsident der HGF, Professor Jürgen Mlynek, unterzeichneten in Anwesenheit des indischen Premierministers Manmohan Singh und der Bundeskanzlerin Angela Merkel das „Memorandum of Understanding“, die Absichtserklärung auf eine enge Zusammenarbeit im IG-SCID. Mit der Zusage über ein Budget von insgesamt 1,5 Millionen Euro für einen Zeitraum von drei Jahren aus dem Impuls- und Vernetzungsfonds des Präsidenten der HGF erstellten das HZI und die Medizinische Hochschule Hannover im Februar 2007 zusammen mit dem ICMR ein Konzept für das gemeinsame Forschungszentrum. Bereits im April 2007 fand in Delhi die offizielle Einweihung des IG-SCID durch Professor Mlynek und Professor Ganguly statt, im Mai unterzeichneten das HZI und das ICMR schließlich das „Cooperation Agreement“. Im Oktober 2007 wurden die Aktivitäten des IG-SCID auf Kooperationen mit der Jawaharlal-Nehru-Universität (JNU) erweitert, verbunden mit einem weiteren „Memorandum of Understanding“ zwischen HZI und JNU. 

 

Forschungsschwerpunkte

Gemeinsam arbeiten die Forscher aus Deutschland und Indien im IG-SCID an verschiedenen Projekten. Sie untersuchen dabei sowohl die Wirts- als auch die Erregerseite. Ziel der Forschung ist ein besseres Verständnis von Infektionskrankheiten, die in Indien besonders problematisch sind. Mit dem gewonnenen Wissen wollen die Forscher neue Impfstoffe und Anti-Infektiva entwickeln.

Beispiel "Hepatitis": 12,5 Millionen Menschen in Indien sind mit dem Hepatitis C Virus infiziert. Bis heute gibt es keinen wirksamen Impfstoff. Ein Viertel der Infizierten entwickelt eine Leberzirrhose oder Leberkrebs. Welches sind die Gründe, die hierzu führen? Hinzukommt, dass in Indien vorrangig der genotyp3 des Virus vorkommt, während dies in westlichen Ländern meist genotyp1 ist. Die Variabilität des Virus spielt bei der Suche nach einem Impfstoff eine wichtige Rolle, damit dieser auch sowohl in Deutschland als auch Indien genutzt werden kann. Die Konstellation "Gleiche Krankheit – veränderter Virus" ist auch bei Hepatitis B ein großes Problem: So gibt es in Indien trotz einer Impfung 45 Millionen Menschen mit einer Hepatitis B-Infektion. Bei diesen Menschen zeigt der Impfstoff keine Wirkung. Das Ziel der deutsch-indischen Kooperation ist es, wirksame und günstige Medikamente zu entwickeln und die indische Biodiversität an Hepatitis-Erregern zu untersuchen.

Beispiel "Genetische Anfälligkeit": Auch die Gene des Wirtes spielen bei Infektionen eine wichtige Rolle. Während für den einen eine Grippe kein Problem darstellt, entwickelt sich beim anderen eine schwere Influenza. Das Projekt "GenetischeAnfälligkeit" untersucht genau dies. Bisher sind nur wenige Gene bekannt, die bei einer erhöhten Anfälligkeit gegenüber einer Erkrankung eine Rolle spielen. Langzeitstudien ermöglichen einen Blick auf die Zusammensetzung der Gene vieler Menschen. Mit ihrer Hilfe können genetische Faktoren identifiziert werden, die Patienten entweder widerstandsfähiger oder empfänglicher für eine bestimmte Krankheit machen.

Weitere Forschungsschwerpunkte des IG-SCID sind Leishmaniose, eine weitgehend vernachlässigte Krankheit, die die Haut und inneren Organe befällt, und Cholera. 90 Prozent der Fälle von innerer Leishmaniose sind auf fünf Länder beschränkt: Bangladesh, Indien, Nepal, Sudan und Brasilien. Dagegen ist die Cholera immer noch ein weltweites Problem, das auch in Indien allgegenwärtig ist. Die Weltgesundheitsorganisation nimmt an, dass nur zehn Prozent der Fälle gemeldet werden. Ein oraler Impfstoff ist zwar für Reisende verfügbar, jedoch kaum erschwinglich für den breiten Markt in Indien. Die Forscher suchen nach neuen Impfstoffkandidaten, die zu einem kostengünstigen Medikament weiterentwickelt werden können.

 

Ausblick

Nicht nur Erreger, die uns bereits infizieren, sondern auch solche, die es erst in Zukunft eventuell könnten, stehen im Fokus des IG-SCID . Von den 1.500 bekannten Mikroben, die Krankheiten bei Menschen auslösen, sind etwa 60 Prozent Zoonosen, also Krankheiten, die vom Tier auf den Menschen übergesprungen sind. Prominente Beispiele hierfür sind Vogel- und Schweinegrippe. In der Vergangenheit waren es HIV, Pocken, Pest und Masern. Ein globales Netzwerk aus Laboren, die die Expertise der westlichen Länder beinhalten, und ein internationaler Wissenstransfer sind notwendig, um zoonotische Erreger dort zu beobachten, wo sie vorkommen und sich zu neuen Bedrohungen für die Menschheit weiterentwickeln. Nur mithilfe von internationalen Forschungskooperationen wie IG-SCID kann in Zukunft der Kampf gegen Infektionskrankheiten entschieden werden.

Partners

 

Indian Council of Medical Research (ICMR)

Jawaharlal-Nehru-Universität (JNU)

Helmholtz-Gemeinschaft Deutscher Forschungszentren

MHH Hannover

 

Groups

Funding agency

Helmholtz

Staphylococcus aureus

The Skin - barrier and target to Staphylococcus aureus: from colonization to invasive infection

Successful strategies of Staphylococcus aureus to colonize and invade the human epithelial barriers and its interaction with the microenvironment

Groups

Funding agency

BMBF - Federal Ministry of Education and Research

Human Nose Habitats

The Microbiota of the Human Nose Habitats - Metagenomic Analyses of their Composition and Dynamics

Groups

Funding agency

BMBF - Federal Ministry of Education and Research

Pseudomonas

Pathogenicity and Biotechnology (3d phase)

New Pseudomonas enzymes acting on 4-substituted but-2-en-4-olides on the third period of the International Research Training Group "Pseudomonas: Pathogenicity and Biotechnology"

 

AG Microbial Interactions and Processes has been participating since the beginning of this European Graduate

School (EGK) carrying out studies on Pseudomonas sp. strain MT1, a chloroaromatic degrader: In this phase the project is entitled:

New Pseudomonas enzymes acting on 4-substituted but-2-en-4-olides

Background and objectives:

4-Chloromuconolactone (4-carboxymethyl-4-chlorobut-2-en-4-olide) and protoanemonin (4-methylenbut-2-en-4-olide) are key intermediates in a 4-membered community degrading chlorosalicylate by a complex net of metabolic interactions and are subject to transformation by either a new type of hydrolase termed trans-dienelactone hydrolase (acting on 4-chloromuconolactone) or thus far unknown enzymes. The proposed project aims on elucidating the structure, mechanism and substrate specificity of the new type of supposedly metal-dependent hydrolase and on the characterization of the metal centers and on the elucidation of the metabolic pathway and enzymes involved in protoanemonin degradation.

Partners

 

Søren Molin, Michael Givskov, DTU Lyngby, Denmark

Groups

Funding agency

Other

STREP

Biotool EC project

PD Dr. Dietmar H. Pieper, Head of the Microbial Interactions and Processes Research Group at HZI, is the coordinator of Biotool consortium, a European Commission funded project (STREP) under the Sixth Framework Programme, Priority 6: Sustainable Development, Global Change and Ecosystems. Code: STREP GOCE 003998

This project is a cooperative cluster of nine labs at leading research institutions from five different countries, aiming, through custom state-of-the-art genomic, proteomic and analytical technologies, the assessment, evaluation and prediction of natural attenuation processes to implement this technology as the accepted key groundwater and soil remediation strategy in Europe.

Groups

Coordinator

Dr. Dietmar H. Pieper (Helmholtz-Zentrum für Infektionsforschung

Funding agency

EU-Projects

AMICO

Adaptation of Microbial Communities to Organic Contaminants in Oligotrophic Aquifers

AMICO EC project (Adaptation of Microbial Communities to Organic Contaminants in Oligotrophic Aquifers) was a consortium of nine European Labs. Code: QLK3-CT-2000-00731

Objectives: To explore the diversity, degradation capacity and resilience of the poorly known microbial communities in pristine and polluted subsurface aquifers, a comparison will be made between a set of logographic communities before and after exposure to a plume of pollutants. A combination of culture-dependent and -independent methods will reveal the functional and genetic characteristics of the communities involved in degradation of a selected range of contaminants (BTEX components) of the chosen aquifer. A detailed study of the genetic and physiological diversity, metabolic potential and adaptability in laboratory-scale model systems will demonstrate how the potential and performance of such communities may be optimised. This will eventually allow experimental manipulation of in-sit enhancement of bioremediation processes by making a rational use of the microbial diversity.

Groups

Funding agency

EU-Projects

MAROC

Molecular Tools for Assessing the Bioremediation Potential in Organohalogen Contaminated Sites

Maroc EC Project (Molecular Tools for Assessing the Bioremediation Potential in Organohalogen Contaminated Sites), a consortium of 5 European labs, funded during the FP5. Code: EVK1-1999-00023

The objectives of this project were:

Characterisation of a representative number of sites concerning their pollution profile and metabolic potential by processing representative samples and data of contaminated sites.

Establish enrichment cultures to isolate a representative fraction of microorganisms with the desired metabolic potential.

Characterisation of the genetic information coding for the degradative potential of single isolates and mixed cultures.

Development of primers and probes, based on previously acquired data, and to verify their specificity using laboratory strains and new isolates and subsequent application of the primers to environmental samples.

Groups

Funding agency

EU-Projects

ACCESS

Innovative approaches to understand complex microbial communities for eco-engineering the degradation of herbicides in stressed agricultural soils

Coordination of the ACCESS EC project: Innovative approaches to understand complex microbial communities for eco-engineering the degradation of herbicides in stressed agricultural soils. A consortium of nine labs from Europe and Latin America. Code: ICA4-CT-2002-10011


A project having as objective to generate a knowledge base for the rational eco-engineering of sites polluted with recalcitrant herbicides atrazine, 2,4-D and analogues.

Objectives:

To understand the roles of complex microbial communities for degradation processes, and adaptabilities of communities to stress conditions we will develop, based on detailed metabolic information, molecular biology tools, to study community functions, interactions and adaptations. Information recruited in model systems will be used in systems of increasing complexity, aiming at the rational manipulation and optimisation of degradative activities, including the contribution of rhizosphere microbial communities.

Groups

Funding agency

EU-Projects

BIO4-CT972040

Rational design of formatted catabolic segments for engineering superior bacterial biocatalysts for degradation of chloro- and nitroaromatics

Coordination of the EC project BIO4-CT972040 (FP4): Rational design of formatted catabolic segments for engineering superior bacterial biocatalysts for degradation of chloro- and nitroaromatics. Code: BIO4972040.

 

Rationale:

The resistance of a variety of pollutants to biodegradation is caused by molecular bottlenecks such as incomplete pathways leading to the formation of dead-end or even toxic metabolites, inappropriate regulation of catabolic pathways or poor transformation rates. However, methods are now available for the construction of new and more effective pathways in order to obtain superior biocatalysts.

The purpose of this project is to identify and, eventually, to remove those biological bottlenecks that prevents biodegradation of recalcitrant pollutants and will focus on non-polar chloro- nitro and methyl-substituted benzenes and their metabolites. An adequate library of genes and enzymes appropriate for transformation will be isolated and characterised in detail. The development of a genetic toolbox for stable and predictable integration of isolated genes into selected host bacteria together with optimization of the performance of the isolated genetic elements will allow a rational assembly of these elements to create superior metabolic pathways.This will lead to microorganisms with increased catalytic potential and efficiency for degradation of xenobiotics, and a better survival in environmental settings.

The objectives of this project are (I) the detail ed genetic and biochemical analysis of catabolic elements as tools for the development of biocatalysts for the degradation of recalcitrant compounds, (2) optimization of the effectiveness of catabolic segments by changes in substrate specificity of critical pathway enzymes, the reconstruction of regulatory circuits and the development of specific tools for the stable assembly of optimised segments in appropriate hosts and (3) the development of new predictable bacterial strains able to mineralise previously recalcitrant pollutants under a variety of environmental conditions.

Groups

Funding agency

EU-Projects

Biomercury

Worldwide remediation of mercury hazards through biotechnology Acronym

Mercury is a priority pollutant because of its extreme toxicity, global atmospheric transport and accumulation in the food chain. Its removal from current industrial emissions as well as from previously polluted sites is therefore mandatory. A unique biotechnological process for removal of mercury from wastewater based on the enzymatic transformation reactions of live mercury resistant bacteria has been developed at GBF, tested for 8 months at a German chloralkali plant and operated at a Czech chloralkali electrolysis factory in full scale for more than two years. This new technology is proven to be efficient, robust, environmentally friendly and cost effective. The aim of the specific support action BIOMERCURY is to

  • evaluate the applicability of the microbe based technology for clean-up of contaminated environments worldwide;
  • monitor the longterm performance of the first industrial microbe based mercury removal plant,
  • compare costs, safety and efficiency of the biotechnological approach with traditional methods;
  • transfer knowledge into developing countries where the problems are most urgent;
  • exchange information with US agencies.

These goals shall be approached by an international consortium which will first conduct case studies on hot spots of pollution as well as on current mercury emitting industries, taking into account technology offers. On this basis, integrated engineering concepts will be developed. They will be communicated to governments and International Agencies with the aim of implementing demonstration or remediation projects.

Partners

 

Technical University of Braunschweig

University of Southampton

GEOtestBRNO

University of Jerusalem

Technical University of Lodz

Jozef-Stefan-Institute

University of Tirana

Almaty Institute of Power Engineering and Telecommunications

University of Cartagena

Istituto de Ciências do Mar

Rutgers University

University of Florida

US Environmental Protection Agency

 

Groups

There are no results

Funding agency

Other

Legionella populations in freshwater systems in Germany, Palestine and Israel

Understanding the ecology and virulence of Legionella spp. populations in freshwater systems in Germany, Palestine and Israel

Immunofluroszenzmikroskopie von Legionella pneumophila im Trinkwasserbiofilm.Immunofluroszenzmikroskopie von Legionella pneumophila (grüne Zellen) in Trinkwasserbiofilm (blau).

Bacteria of the genus Legionella cause waterborne infections resulting in severe pneumonia. In Europe, 70% of the cases of the so-called Legionnaires’ disease (LD) originate from strains of L. pneumophila serogroup (Sg) 1, 20% from other L. pneumophila serotypes and 10% from other Legionella species. In contrast, in the Middle East most legionella infections are due to L. pneumophila Sg3.

Overall objective

The overall objective of this project is to advance current knowledge on the ecology of legionella in freshwater systems, the environmental factors affecting their occurrence, virulence potential and infectivity and to understand their transmission to humans. We will analyze the major environmental factors regulating the abundance of legionella, such as grazing and assimable dissolved organic carbon, because the occurrence of these heterotrophic bacteria in aquatic habitats is highly dependent on these factors.

Integrated molecular approach 

We will use an integrated molecular approach based on high-resolution diagnostics of environmental samples and clinical isolates to determine the abundance, activity and virulence potential of Legionella populations in-situ. Combining environmental and molecular epidemiological data, we aim at understanding the link between ecology and population dynamics of legionella and cases of LD.

Epidemiology of legionella

The project will result in a novel understanding of the molecular epidemiology of legionella and provide new surveillance tools and strategies to prevent LD.

Partners

Project Leader - Germany

Dr. Priv. Doz. Manfred Höfle
Helmholtz Centre for Infection Research
Dept. Vaccinology and Applied Microbiology
Inhoffenstraße 7, 38124 Braunschweig, Deutschland
Tel. +49 531-6181-4234

Palestine

Prof. Dr. Dina M. Bitar
Al-Quds University, Faculty of Medicine, Department of Microbiology and Immunology
P.O. Box 19356, Jerusalem, Abu Dies, Palestine
Tel: +972 22799203

Israel

Dr. Malka Halpern
University of Haifa, Faculty of Natural Sciences, Department of Science Education - Biology
Oranim, Tivon, Israel, 36006
Tel.: +972 49838978

Leader

Groups

There are no results

Funding agency

Other

AQUA-CHIP

Development and validation of a DNA-chip technology for the assessment of the bacteriological quality of bathing and drinking water

Groups

There are no results

Coordinator

Helmholtz-Zentrum für Infektionsforschung

Funding agency

EU-Projects

Soil

Soil organic matter and microbial diversity as parameters controlling important soil functions

Groups

There are no results

Funding agency

BMBF - Federal Ministry of Education and Research

Aquatic resources

System-integrated environmental biotechnology for remediation of organically and inorganically polluted aquatic resources

Groups

There are no results

Coordinator

Helmholtz-Zentrum für Infektionsforschung

Funding agency

BMBF - Federal Ministry of Education and Research

MARGENES

Marine bacterial genes and isolates as sources for novel biotechnological products

Groups

There are no results

Coordinator

Helmholtz-Zentrum für Infektionsforschung

Funding agency

EU-Projects

Bacterioplankton community structure

Seasonal dynamics and controlling mechanisms of bacterioplankton community structure in the Western Mediterranean Sea

Groups

There are no results

Funding agency

EU-Projects

Microbial ecology

Application of molecular methods for microbial ecology and biological safety

Groups

There are no results

Funding agency

EU-Projects

Microbial diversity

Exploration of Microbial diversity

Groups

There are no results

Funding agency

EU-Projects

Molecular RNA

Determination of successions of bacterioplankton in lakes by comparative analysis of low molecular RNA

Groups

There are no results

Funding agency

DFG - German Research Foundation

HRAMI 1

High resolution automated identification of microorganisms

Groups

There are no results

Funding agency

EU-Projects

Listeria monocytogenes

Invasion by Listeria monocytogenes

The facultative intracellular human pathogen L. monocytogenes produces a distinct number of virulence factors, that usually mimic host cell processes leading e.g. to invasion and propagation within the host. In the past we have determined the high resolution crystal structures of internalins and internalin-like proteins from L. monocytogenes. Common to all these proteins is the presence of a so-called leucine-rich repeat (LRR) domain that specifically interacts with host cell receptors during invasion. The structure of the complex between the receptor-binding domain of internalin A and the N-terminal domain of human E-cadherin (Schubert, 2002) provided a detailed picture of the first step of listerial infection in the human intestine. It also explained the known host tropism of L. monocytogenes towards humans but not mice. For further information and follow-up projects see this link.

Recently we have solved the structure of the complex between second listerial invasion protein InlB with its human receptor Met, the natural tyrosine kinase receptor of hepatocyte growth factor/scatter factor (HGF/SF), which initiates uptake of the bacteria by many different tissues. The structure shows that InlB predominantly interacts via its LRR-domain with the Ig1-domain of Met in constrast to HGF/SF which targets the N-terminal Sema-domain (Niemann, 2007). We are currently investigating how the InlB-Met-interaction leads to uptake of the bacteria by the host.

Groups

Funding agency

Other

Y. enterocolotica

Type III secretion system chaperones and effectors

We are working on several components, effectors and chaperones of the Y. enterocolotica type III and enteropathogenic Escherichia coli (EPEC) secretion systems. For efficient secretion, type III secretion system effectors require specific  chaperone proteins that keep the effectors in a partially unfolded state prior to transfer through the injectisome.

 

After having solved the structure of the YopT chaperone SycT (Büttner et al, 2005) we recently solved the structure of SycD, which is responsible for translocator proteins showing a tetratricopeptide repeat fold (Heinz, 2007, in press) . 

 EPEC exploits the human adapter protein Nck as part of its infection strategy. During infection Nck specifically recognizes the phosphorylated translocated intimin receptor (Tir) which is inserted into the host membrane and eventually leads to dynamic bacteria-presen­ting protrusions of the plasma membrane known as pedestals. Using surface plasmon resonance spectroscopy, peptide epitope scanning and crystal structure determination of the Nck1 and Nck2 SH2-domains in complex with Tir-derived phosphopeptides we were able to investigate and differentiate the phosphopeptide binding affinities of Nck1 and Nck2 (Frese et al., 2006).

Groups

Funding agency

Other

Biosynthesis

Enzymes of tetrapyrrole biosynthesis

The tetrapyrrole biosynthesis is a ubiquitous and central anabolic pathway leading to the formation of essential tetrapyrroles such as heme, chlorophyllandvitamin B12from simple precursors. In a long-standing collaboration with Dieter Jahn (Technical University Braunschweig) we are systematically investigating the structural and functional elucidation of enzymes belonging to this pathway.

Recent examples are the structures of coproporphyrinogen IX oxidase and aminolevulinic acid synthase.

The O2-independent coproporphyrinogen IX oxidase represents the first structure of an enzyme belonging to the ubiquitous family of "Radical SAM enzymes". Our future goal is to elucidate the catalytic mechanism of this complicated enzyme from structural studies, as well as site-directed mutagenesis and use of synthetic inhibitors (in cooperation with Markus Kalesse, University of Hannover/HZI). (Layer et al, 2006)

Finally we have solved and analyzed the crystal structure of aminolevulinic acid synthase, the first enzyme of tetrapyrrole biosynthesis in mammals and yeast, in complex with both substrates. Mutations in this enzyme lead to rare blood disorders and other diseases. With the structure of aminolevulinic acid synthase the structures of all enzymes of heme biosynthesis have finally been determined.  (Astner et al, 2005).

 Future research will focus on the catalytic mechanism and substrate binding of selected enzymes.

Partners

 

University of Hannover

Technical University Braunschweig

Groups

Funding agency

Other

Renal cell carcinoma

Characterization of the human kinome in renal cell carcinoma

This project comprises the most extensive systematic kinome analysis based on chemical and quantitative proteomics that targets kinases and their phosphorylations in ex-vivo RCC tissues and their healthy counterparts. The regulated kinase subset comprises both proof-of-concept kinases that were already linked to RCC and, importantly, also novel candidates as well as kinases of other cancer-relevant processes. This study therefore hints at prospective therapeutic approaches, by complementing our knowledge and understanding of RCC, i.e. its development and specific signal networks.

Leader

Groups

Speaker

Dr. Susanne Freund (Helmholtz-Zentrum für Infektionsforschung)

Funding agency

Other

Met signaling pathway

Phosphoproteome analysis of the Met signaling pathway

The human Met signaling pathway plays a crucial role in the cellular response to growth factors. Once stimulated by its physiological ligand hepatocyte growth factor (HGF), the Met receptor initiates a signaling cascade via phosphorylations, which leads to proliferation, motility and cell survival. In cancer, this pathway is overexpressed and causes metastasis formation. The surface protein internalin B of Listeria monocytogenes is also able to bind and activate Met, which leads to the pathogen’s invasion into the host cell.
The aim of this project is to shed more light on the pathways downstream of the Met receptor and to understand the influence of L. monocytogenes on the signaling using phosphoproteomics.

Leader

Groups

Speaker

Evelin Berger (Helmholtz-Zentrum für Infektionsforschung)

Funding agency

Other

HSV-Infection

Microtubule-dependent motor protein dynamics in HSV-infection

Many pathogens, such as the herpes simplex viruses (HSV), use the cellular microtubule network and its associated motor proteins for intracellular movement. The recruitment of molecular motors to microtubules depends on the tyrosination status of microtubules, thus the tubulin-tyrosin-ligase (TTL) might influence intracellular transport of pathogens like HSV. In this project, we characterize the interactome of microtubules and their associated motor proteins in wild type and TTL-deficient cells, and furthermore aim to validate and functionally characterize novel TTL- and HSV-dependent motor and adapter proteins.

Leader

Groups

Speaker

Björn Bulitta (Helmholtz-Zentrum für Infektionsforscher)

Funding agency

Other

NK-Cells

Proteomic characterization of distinct NK cell maturation stages

NK cells are cytotoxic lymphocytes and can be subdivided into distinct subsets of different maturation stages due to their presentation of certain surface antigens like CD56, CD57 and CD3. Our aim is the proteomic characterization of these distinct primary NK cell subsets isolated from healthy human blood donors in order to get a deeper insight into the mechanisms of cytotoxicity and differentiation on a molecular level by using quantitative LC-MS/MS techniques.

Leader

Groups

Speaker

Maxi Scheiter (Helmholtz-Zentrum für Infektionsforschung)

Funding agency

Other

DUB

Novel activity-based probes for characterization of deubiquitinating enzymes

Ubiquitylation is a reversible posttranslational modification of proteins that is implicated in many key cellular functions. Deubiquitinating enzymes (DUBs) act as antagonists of ubiquitin ligases to remove covalently bound ubiquitin moieties from modified proteins and thereby contribute to the regulation of several signaling events. These enzymes have emerged as promising therapeutic targets due to their wide-ranging involvement in cellular processes.
We develop activity based probes (ABPs), which are reactive substrate analogs that enable the enrichment of active DUBs and facilitate their characterization. This technology allows us to investigate the regulation of the ubiquitin system in infection processes and provides significant information to advance the drug discovery with greater strides.

Groups

Speaker

Alexander Iphöfer (Helmholtz-Zentrum für Infektioonsforschung)

Funding agency

Other

Internalin B

Signal network analyses of the Met pathway activated by the invasin Internalin B from Listeria monocytogenes

This project aims at the characterization of the host signal network that is manipulated in the process of Listeria monocytogenes cell invasion mediated by its surface protein Internalin B (InlB). Thereby InlB, amongst others, interacts with the human Met receptor, whose original ligand is the hepatocyte growth factor (HGF), which leads to the endocytosis of the pathogen. Due to the fact that 500 human protein kinases virtually control every signalling pathway, kinase enrichment chromatography and time-resolved phosphoproteome analyses are used to reveal those kinases responding to and involved in the process of InlB stimulation. Candidates of newly found kinases are functionally analyzed with respect to Listeria invasion and physiological Met phenotypes.

Leader

Groups

Speaker

Kirstin Jurrat (Helmholtz-Zentrum für Infektionsforschung)

Funding agency

Other

Listeria

Ubiquitin and Ubiquitin-like host modifications in Listeria infection

Although it is known that ubiquitin and ubiquitin-like modifiers are utilized during invasion of Listeria monocytogenes, the underlying mechanisms are only sparsely described. Therefore, a systematic and protein-based approach to retrieve a detailed insight in the ubiquitin-mediated processes shall be established in this project. In combination with a subsequent functional characterization of candidate proteins, this study will provide working points for the specific impairment or inhibition of cell invasion by Listeria.

Leader

Groups

Speaker

Anne Kummer (Helmholtz-Zentrum für Infektionsforschung)

Funding agency

Other

Cytomegalovirus

Molecular mechanisms of persistent antigenic stimulation in cytomegalovirus infection

This project is a result of a starting grant by the European Research Council (ERC), which was awarded to our group in 2011.


Cytomegalovirus (CMV) induces a T-cell response of unique magnitude, and CMV-specific T-cells dominate the memory compartment of latently infected hosts, yet the reasons for such a strong response remain unclear.


This project aims to clarify the mechanisms of CMV immunodominance on a molecular level. Using a model of mouse infection with recombinant mouse CMVs, we will explore the conditions upon which viral peptides induce immune responses, and the possibilities to improve or suppress the antigenic induction.


Improved understanding of the conditions upon which CMV activates T-cells may allow us to develop therapeutic strategies for the control of CMV disease in immunosuppressed patients undergoing organ transplantation procedures. Potentially, this knowledge may allow us to harness the immune potential of CMVs and generate CMV-based vaccine vectors against other infections.

Groups

Funding agency

Other

MCMV-Infection

IFN-mediated control of chronic CMV infection

Type I interferons exert strong inhibitory effects on the de novo infection of cells by MCMV. This is in line with the fact that MCMV infection induces the production of large amounts of type I IFNs.

However, the contribution of type I IFNs to latency and reactivation of chronically infected animals remains unclear: IFNs might have controlling effects. Alternatively, the induction and/or function of type I IFNs could be suppressed by viral evasion mechanisms in chronicity. The planned experiments are carried out in (transgenic) mice and in a newly developed in vitro latency model.

Groups

Funding agency

Other

SFB 587: Teilprojekt B12

Untersuchungen zur Immunregulation bei akuter und chronischer CD4+ T-Zell-vermittelter Erkrankung der Lunge

Im Rahmen dieses Forschungsprojektes sollen neue Erkenntnisse zu den grundlegenden Mechanismen T-Zell-vermittelter Immunität und peripherer Toleranzinduktion bei Erkrankungen der Lunge gewonnen werden. Hierbei sollen im transgenen Mausmodell die autoreaktiven T-Zellen, die Antigen-exprimierenden  Typ II Epithelzellen und die pulmonalen Dendritischen Zellen näher charakterisiert werden. Zudem soll die Aufrechterhaltung und der Verlust von immunologischer Toleranz in der Lunge bei Infektionen untersucht werden.

 

Die mukosalen Oberflächen des Respirationstraktes stellen dünne und - aufgrund ihrer physiologischen Funktion des Gasaustausches - äußerst durchlässige Barrieren zwischen Körperinnerem und der Umgebung dar. Diese exponierte Lage bedingt, dass immunologische Reaktionen in der Mukosa einer hochsensiblen Regulation unterliegen, um angemessen auf inhalierte, harmlose, antigene Partikeln einerseits und gefährliche Pathogene andererseits reagieren zu können. Störungen in dieser sensiblen immunologischen Balance können zu schädlichen Immunreaktionen und zu Erkrankung führen.

Die zentrale Bedeutung von T-Lymphozyten bei Immunreaktionen der Lunge wird zunehmend erkannt, und es ist inzwischen akzeptiert, dass T-Zellen bei der Pathogenese verschiedener Lungenerkrankungen eine wichtige Rolle spielen. Obwohl die Bedeutung von CD4+ T-Zellen bei verschiedenen Erkrankungen der Lunge bekannt ist, sind die Mechanismen, die der Induktion und Regulation von CD4+ T-Zell-vermittelten Immunreaktionen in der Lunge zugrunde liegen, bislang nur sehr unvollständig verstanden.


Um T-Zell-abhängige Reaktivität gegen lungenspezifische Antigene besser zu charakterisieren und so das grundsätzliche Verständnis entzündlicher Prozesse in der Lunge zu verbessern, haben wir ein transgenes Mausmodell für eine CD4+ T-Zell-vermittelte Erkrankung der Lunge etabliert. Hierfür wurde eine transgene Maus generiert, die das Modellantigen Hämagglutinin (HA) unter der transkriptionellen Kontrolle des Surfactant Protein C (SPC) Promoters spezifisch in den alveolaren Typ II-Epithelzellen (AECII) der Lunge exprimiert. Eine Kreuzung dieser SPC-HA transgenen Maus mit einer Maus, die einen MHC Klasse II-restringierten T-Zellrezeptor spezifisch für das Hämagglutinin (TCR-HA) trägt, führt bei den doppelt transgenen SPC-HA x TCR-HA Mäusen zur Entwicklung einer autoimmun-vermittelten, progressiven interstitiellen Pneumonitis. Aus unseren bisherigen Forschungsergebnissen zur funktionellen Charakterisierung autoreaktiver CD4+ T-Zellen haben wir fundierte Hinweise auf die Induktion regulatorischer T-Zellen (Tregs) bei chronischer Antigenstimulation in der Lungenschleimhaut gewonnen.

 

Im Rahmen des SFB 587-geförderten Projektes sollen neue Erkenntnisse zu den grundlegenden Mechanismen T-Zell-vermittelter Immunität und peripherer Toleranzinduktion bei Erkrankungen der Lunge gewonnen werden. Hierbei bildet die umfassende Charakterisierung des AECII – T-Zell – Crosstalks in der Lunge einen Schwerpunkt unserer Forschungsaktivitäten. Eine umfangreiche Charakterisierung der pulmonalen autoreaktiven CD4+ T-Zellen hat ergeben, dass chronische Antigenstimulation in der Lungenschleimhaut zur Induktion Foxp3+ regulatorischer T-Zellen führt. Unsere Untersuchungen zur Beteiligung der AECII an entzündlichen Prozessen in der Lunge haben gezeigt, dass die Erkennung des Selbstantigens durch CD4+ T-Zellen zu massiven Veränderungen im AECII-Genexpressionsprofil führt. Des Weiteren konnten wir zeigen, dass diese Zellen wichtige Funktionen bei der Induktion und Regulation T-Zell-vermittelter Entzündung in der Lunge aufweisen. In vitro Experimente belegen, dass AECII aus der erkrankten Lunge vermehrt Faktoren sekretieren, die die T-Zellproliferation inhibieren und die Induktion regulatorischer T-Zellen fördern. Zudem untersuchen wir in diesem Mausmodell für T-Zellvermittelte Entzündung der Lunge den Einfluss von Infektionen auf die Aufrechterhaltung und den Verlust von immunologischer Toleranz in der Lunge. Ziel ist ein besseres Verständnis der komplexen immunologischen Mechanismen, die zum Verlust von Selbsttoleranz bei Infektionen in der Lunge führen können. Eine bessere Kenntnis der Pathomechanismen bei chronischen Erkrankungen der Lunge sowie bei Infektionen stellt die Grundlage für eine gezielte therapeutische Modulation der mukosalen Immunantwort dar.

 

Leader

Groups

Speaker

Prof. Dr. med. Gesine Hansen (MHH)

Funding agency

DFG - German Research Foundation

HCC

Zelluläre Immuntherapie der HCV-Infektion durch HCV-verursachtes HCC

Weltweit sind derzeit mehr als 170 Millionen Menschen chronisch mit dem Hepatitis C-Virus (HCV) infiziert. Akute HCV-Infektionen verlaufen üblicherweise asymptomatisch, wobei jedoch 50 bis 90 Prozent der infizierten Patienten nicht in der Lage sind, das Virus erfolgreich zu eliminieren und folglich eine chronische Infektion entwickeln. Diese führt nicht selten zu Leberzirrhose und zur Entwicklung von Leberkrebs. Trotz dieses enormen medizinischen Problems gibt es derzeit nur äußerst begrenzte Therapiemöglichkeiten und noch keinen Impfstoff gegen HCV.

Im Rahmen des von der HGF geförderten Forschungsprojektes entwickeln wir eine auf dendritischen Zellen (DCs) basierende Immuntherapie gegen das HCV. Diese beruht auf dem in vivo Targeting von Antigenen zu reifenden DCs. DCs fungieren als eine Art „molekularer Schalter“ im Immunsystem. Während die Aktivierung von T-Zellen durch unreife DCs zur Entwicklung von T-Zelltoleranz führt, induzieren reife DCs eine robuste T-Zellantwort, die essentiell für die Eliminierung des HCV ist. Um HCV-spezifische Antigene in DCs einzuschleusen, koppeln wir ausgewählte virale Antigene an einen Antikörper gegen den Endozytose-Rezeptor DEC-205, der auf der Oberfläche von DCs exprimiert wird. Die Verabreichung dieses Antikörper-Antigen-Komplexes in Kombination mit DC-aktivierenden Substanzen führt zur Aktivierung HCV-spezifischer T-Zellantworten. Da es derzeit keine geeigneten Kleintiermodelle für HCV-Infektionen gibt, testen wir die Effektivität dieser Immuntherapie mittels Surrogat-Infektionen in Mäusen.

Groups

There are no results

Funding agency

Helmholtz

Influenzapneumonie

Rolle der alveolaren Typ II-Epithelzellen und des Toll-like Rezeptor 7 für die erhöhte Suszeptibilität gegenüber bakterieller Superinfektion bei Influenzapneumonie

Eine retrospektive Untersuchung der Spanischen Grippe von 1918/19, einer hinsichtlich der Zahl ihrer Opfer und der weltweiten Verbreitung einzigartigen Pandemie, hat ergeben, dass die überwiegende Mehrheit der Opfer nicht an den primären Folgen der Infektion mit dem Influenza A-Virus (IAV) verstarb, sondern an einer außergewöhnlich hohen Rate bakterieller Superinfektionen, insbesondere mit Streptococcus pneumoniae. Dies gilt auch für spätere Grippe-Pandemien in den 1950er und 1960er Jahren und auch für die kürzlich beendete Schweinegrippe-Pandemie. Die erhöhte Anfälligkeit (Suszeptibilität) gegenüber bakteriellen Infektionen nach einer IAV-Infektion findet man auch im Mausmodell. Wir haben in der Vergangenheit erfolgreich ein solches Tiermodell für die IAV – S. pneumoniae – Superinfektion etabliert, in dem wir zeigen konnten, dass IAV-infizierte Mäuse deutlich häufiger infolge einer Sepsis nach einer S. pneumoniae-Infektion versterben als nicht IAV-infizierte Mäuse. Die Mechanismen, die der transienten immunologischen Reaktionsunfähigkeit gegenüber bakteriellen Erregern zugrunde liegen, sind weitgehend unklar.

Die Oberfläche des Respirationstraktes ist eine dünne und äußerst durchlässige Barriere zwischen Körperinnerem und der Umgebung. Während die Rolle des Epithels ursprünglich auf diese Barrierefunktion reduziert wurde, haben Arbeiten der vergangenen Jahre zunehmend gezeigt, dass Alveolar-Epithelzellen (AEC) eine Vielzahl immunologisch bedeutender Funktionen aufweisen und eine wichtige Verbindung zum adaptiven Immunsystem darstellen. Ob die durch IAV-Infektion veränderte Physiologie von alveolaren Typ II-Epithelzellen (AECII) eine Rolle bei der bakteriellen Superinfektion spielt - entweder durch immunologische Überaktivierung oder Immunsuppression - ist jedoch weitestgehend unverstanden.

Wir untersuchen aktuell, inwiefern die durch IAV-Infektion veränderte Physiologie von AECII eine Rolle für die erhöhte Suszeptibilität gegenüber S. pneumoniae-Infektionen spielt. In diesem Kontext soll auch die Funktion des Toll-like Rezeptors 7, dessen Aktivierung antimikrobielle Funktionen in IAV-infizierten Zellen einleitet, näher charakterisiert werden. Basierend auf umfangreichen Transkriptomanalysen von AECII vor und nach einer IAV-Infektion soll ein umfassender Einblick in die Virus-induzierten Veränderungen im genetischen Programm und immunologischen Profil dieser Zellen gewonnen werden. Damit verbindet sich die Hoffnung, neue therapeutische Optionen für künftige Influenza-Pandemien zu erhalten.

Groups

There are no results

Funding agency

DFG - German Research Foundation

Mucosal

Mucosal vaccination

The optimization of the immunogenicity of antigens delivered by the mucosal route is a main priority, since mucosal vaccination leads to the stimulation of immune responses at the sites where the first line of defense against infections is laid. This results in protection not only against disease, but also against infection (i.e. colonization), thereby reducing the risk of horizontal transfer from infected individuals to susceptible hosts.

Therefore, this project focuses on the development of new adjuvants, which are amenable for mucosal vaccination. Their underlying mechanisms of action are elucidated to facilitate the fine tuning of the elicited responses, as well as to assess the potential risk of side effects associated with their use in humans. The most promising candidates are been exploited for the development of vaccine candidates against specific diseases.

Groups

Funding agency

Other

HIS mice

Improving predictability of preclinical data

To increase predictability of the success rates of vaccine and drug candidates transferred into the clinic, advanced animals models are being established that would allow a cost-efficient screening, selection and prioritization of different candidates and formulations.

The goal of this project is to create small animal models based on humanized mice for testing vaccines and drugs against pathogens with tropism for human cells. Specifically, we aim to generate mice with a functional human immune system (HIS), functional human liver cells (HuHep) or harboring both tissues (HIS-HuHep). These three humanized mouse models will allow us to identify vaccine and drug candidates against lymphotropic (e.g., HIV) and hepatotropic (e.g. HCV, HBV) pathogens. The humanized animals would represent a valuable technology platform not only for a robust preclinical evaluation of the immunogenicity, efficacy and safety of products aimed at treating diseases with highly predictive value for humans, but also for the generation of human monoclonal antibodies (mAbs) that can be used for therapeutic and diagnostic purposes.

Groups

Funding agency

Other

HCVAX

Novel vaccines against Hepatitis C using nanotechnology

Anti-viral treatments against hepatitis C virus (HCV) suffer from many disadvantages, and infections usually become chronic. While an efficient anti-HCV vaccine would help alleviate the problems of this disease, such a vaccine does not yet exist. Thus, the goal of the HCVAX consortium, which is funded by the EuroNanoMed Joint Transnational Initiative of the European Union is to develop such a vaccine

The HCVAX vaccines are generated from innovative, biocompatible nanogels carrying RNA-replicon vaccines. The latter are modified swine fever virus genomes - incapable of infecting human cells as a biosafety measure – encoding HCV antigens, yet unable to generate infectious virus. For focused vaccine delivery, the nanogel carrier is designed to target and introduce the RNA replicon cargo into dendritic cells, the pivotal cells for inducing efficient immune responses. Further, innovative adjuvants will be screened for increasing the efficacy of these vaccines. Briefly, we will test adjuvants emerging from our pipeline in combination with the nanogels and replicons for their capacity to direct the Nanogel carrier to dendritic cells and to modify and optimize the elicited immune responses as needed for  effective vaccination against HCV.

Promising formulations will be identified through in vitro screening assays, and evaluated pre-clinically in vivo, to prioritize them for clinical development.

Groups

Coordinator

Dr Kenneth C. McCullough, Institute of Virology and Immunoprophylaxis Mittelhäusern, Switzerland

Funding agency

BMBF - Federal Ministry of Education and Research

Rebirth

Tolerance for Translation of Regenerative Therapy

The goal of the Excellence Initiative REBIRTH (Regenerative Biology and Reconstructive Therapies) is to strengthen cutting-edge research in Germany and to improve its international competitiveness establishing an internationally visible scientific network for regenerative medicine relating to the heart, blood, lungs and liver. Within this cluster a research area is designed to identify new molecular targets for therapeutic interventions and proof-of-principle of new regenerative therapies in non-clinical models. In this context, researchers are also improving technologies required for the generation, delivery and biosafety monitoring of regenerative drugs and advanced therapeutic medicinal products (ATMPs; i.e. cell therapy, gene therapy and tissue engineering). The developed models cover lymphohaematopoietic, cardiac, pulmonary, he­patic and endocrine (diabetes mellitus) diseases. Furthermore, modes of inducing tolerance and regenerating immunity in conditions of undue tolerance (i.e. cancer) were also investigated. Therefore, one of our most important goals is the identification of compounds facilitating or inhibiting the de novo generation of Treg as well as acting on existing Treg. To this end, in vitro screenings will be performed based on DC, Tregs and effector CD4 and CD8 T cells derived from WT and transgenic animals. Immunomodulators will be exploited to address the specific needs of activities within the Tolerance Group, as well as in other external REBIRTH subprojects. Another important goal is the improvement of the humanized mouse model (HIS) in order to increase the predictive value of preclinical studies. The resulting enhanced models will be exploited in the context of other REBIRTH subprojects.

Groups

Chagas disease

Development and testing of prophylactic and therapeutic vaccine candidates against Chagas disease

Chagas disease is caused by Trypanosoma cruzi and affects 16-18 million people in Central and Latin America, leading to chronic disease with severe incapacitation. It is characterized by an acute phase followed by an indeterminate stage that can last for years without signs or symptoms. Nearly 30% of patients’ progress to a chronic phase in which different types of pathology appear. Chemotherapy of Chagas disease has limited efficacy and is not innocuous. Recent studies suggest that parasite persistent infection is responsible for chronic manifestations, suggesting the importance of developing prophylactic or therapeutic vaccines. However, certain candidate antigens (Ag) seem to be involved in immune escape. Due to the natural infection cycle and logistic constraints, it would be a plus to develop a mucosal vaccine. Different antigens from this parasite will be used to develop mucosal vaccine formulations, which will be tested for immunogenicity to select appropriate Ag combinations or to design chimeric proteins based on Ag domains lacking immune evasion properties. The efficacy of the resulting candidates will be assessed in acute and chronic infection models.

This project is funded by the German Federal Ministry of Education and Research (BMBF) and the Ministerio de Ciencias, Tecnología e Innovación Productiva (MINCYT).

Groups

Funding agency

BMBF - Federal Ministry of Education and Research

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