How do bacteria, viruses, parasites and fungi make us sick? And how does our immune system defend our body? These are the questions we address at the Helmholtz Centre for Infection Research (HZI). Our goal: To set up the basis for new diagnostic tools, new active agents and new therapies against infectious diseases.
Together with 100 guest scientists from all over the world, our researchers take on this urging task. With sophisticated laboratory techniques they observe pathogens and immune cells during the moment of infection. They analyse the molecular structure of the “weapons” that pathogens utilise to invade a host cell – and develop methods to defuse them. They seek for substances from nature or lab that neutralise pathogens, prevent infections or are even able to cure them. They use high tech analytical devices and study the processes of infections in cell culture, in complex elaborating computer simulations, and in mice – for a healthier future.
By that, the Helmholtz Centre for Infection Research follows the aims of the Helmholtz Association of German Research Centres and contributes to the successful implementation of the German Government’s research strategy. The scientific activity of the Helmholtz Association is organized in six research fields with different research programmes. Every five years the 18 institutes of the Helmholtz Association have to apply for funding – the institutes’ research programmes compete with each other.
The HZI focuses on the programme “Infection Research”. This programme aims to solve the growing challenges in the field of infection research: Increasingly appearing resistances to antibiotics, easier transfer paths for pathogens due to our high mobility and the climate change as well as the growing number of elder people benefit the spread of infectious diseases. In addition to that, so far unknown diseases like SARS, bird or swine flu break out. Known pathogens suddenly increase their aggressiveness, as for example EHEC during the 2011 epidemic in Northern Germany.
The single research projects of the HZI are subordinated to three topics within the research programme:
This programme structure reflects the particular challenges posed by infectious diseases. Controlling these diseases requires detailed knowledge on the levels of the host, the pathogen and the treatment or prevention options, as shown in the triad in the figure above. An intensive contact and exchange between the different topics secures the programme’s success.
Based on the three topics, overarching “Research Foci” have developed. They reflect the interdisciplinary strategic alignment of the programme and deal with the clinically relevant focal projects „Antimicrobial Resistance“, „Gastrointestinal Bacterial Infections“, „Chronic Viral Infections“, „T Cell Targeting and Vaccination Strategies“ and „Epidemiology for Public Health Solutions“.
Research Foci at HZI
To focus on clinical questions of major relevance, HZI has developed a dynamic, integrative and interdisciplinary research portfolio involving expertise and technological developments of each topic. The resulting research foci form a significant part of HZI’s research portfolio and involve basic, pharmaceutical and clinically oriented research. They are ambitious, interdisciplinary projects combining expertise from all three topics to tackle a particular health problem.
Currently five major cross-topic research foci have been established (see Figure). All of these are driven by the expertise and interest of HZI researchers. Importantly, they also build on the strengths of the centre’s cooperation partners. They are highlight examples of focal areas that are addressed by the integrated approach of the Programme “Infection Research”. In addition, they are strongly connected to complementary activities funded by the Federal Ministry of Education and Research (BMBF), including the German Centre for Infection Research (DZIF), the German Research Foundation (DFG), as well as international programmes funded by the EU and other funding organizations.
These research foci are:
- Antimicrobial Resistance (AMR)
- Tackling Gastrointestinal Bacterial Infections (GAST)
- Approaches against Chronic Viral Infections (CVIR)
- T cell Targeting and Vaccination Strategies (TVAC)
- Epidemiology for Public Health Solutions (EPI)
RESEARCH FOCUS: ANTIMICROBIAL RESISTANCE (AMR)
Increasing occurrence of antimicrobial resistance is a severe challenge, particularly in the light of the scarcity of new candidates in drug discovery. Scientists in the research focus AMR combine expertise in various fields and long-standing experience in industry or industrial-academic collaborations to address these challenges, pursuing a multi-pronged strategy. They investigate the molecular mechanisms causing resistances, explore innovative strategies against pathogens and identify and optimise novel anti-infective compounds.
The long-term objectives include the development of tools for early diagnosis and targeted antibiotic treatment, new methods to selectively block pathogenic mechanisms – thus preventing the emergence of resistances – and the development of novel natural antibiotics exhibiting new modes of action. Sustainable biotechnological production of these novel antiinfectives provides sufficient material for late preclinical studies.
The research of AMR scientists has already led to a number of novel compounds from natural sources with new modes of action, including potential therapeutics against Gram-negative bacteria, which are particularly difficult to treat.
RESEARCH FOCUS: TACKLING GASTROINTESTINAL BACTERIAL INFECTIONS (GAST)
Currently only limited options for the effective treatment of acute and chronic enteric infections are available. To gain a comprehensive understanding about the course of infection and the complications associated with enteric infections, the research focus GAST combines expertise to identify essential virulence mechanisms of enteric pathogens and to characterise the complex interplay between pathogens, the host immune system and the microbial ecosystem of the gut (gut microbiota). Newly developed technologies enabled the discovery of essential virulence strategies and an advanced understanding of the molecular mechanisms of bacterial pathogenicity factors leading to the identification of novel promising drug targets.
RESEARCH FOCUS: APPROACHES AGAINST CHRONIC VIRAL INFECTIONS (CVIR)
Chronic viral infections by hepatitis and herpes viruses are causing a severe global disease burden. Recently, effective treatment for hepatitis C virus (HCV) infections has become available, but it is challenging to deliver it to all in need. Cytomegalovirus (CMV) therapies are limited by side effects and viral resistance. Vaccines are still lacking for both HCV and CMV, and the understanding of basic mechanisms of pathogenesis, immune control and viral evasion are incomplete. The research focus CVIR dissects principles that govern HCV and CMV persistence including mechanisms of innate immune control and viral evasion. By exploring mechanisms of protective or failing T cell responses and determinants of protective humoral immunity, it aims to contribute to the development of new preventive measures.
RESEARCH FOCUS: T CELL TARGETING AND VACCINATION STRATEGIES (TVAC)
Effective therapies and vaccines are still missing for many emerging and re-emerging pathogens. This is particularly true for vulnerable individuals that are at high risk for severe forms of infection and poor responders to intervention. Thus, the research focus TVAC has established experimental and clinical activities to fill existing knowledge gaps by developing immune-based approaches to prevent or treat resilient infections in vulnerable patients. The research activities contribute towards a better understanding of differential host responsiveness to infection and vaccination (e.g. influenza). New technologies were also developed to derive effective immune-based strategies for the prevention and treatment of infections.
RESEARCH FOCUS: EPIDEMIOLOGY FOR PUBLIC HEALTH SOLUTIONS (EPI)
The research focus EPI addresses the societal dimension of infectious diseases in order to develop corresponding public health solutions. The Surveillance Outbreak Response Management and Analysis System (SORMAS) is a prominent example for a tool developed by HZI, which is already being used to control disease outbreaks in Nigeria and contributing to the understanding of infectious diseases. Special infection modules within the German National Cohort (GNC) developed by HZI will allow the investigation of how infections contribute to non-infectious diseases and vice versa, ultimately leading to novel prevention strategies. Furthermore, the research focus EPI is developing novel diagnostics, such as differential serology, which allow to measure effectiveness of vaccination strategies on population level on the basis of immunological biomarkers.