International call for 16 PhD candidates in infection research

Jumbo bacteriophages represent a rapidly emerging frontier in molecular microbiology due to their exceptionally large genomes, complex intracellular organization involving phage-derived nucleus-like compartments, and extensive repertoire of uncharacterized genes involved in host takeover. However, functional investigation of jumbo phages remains limited by the lack of efficient genetic engineering tools and high-throughput screening approaches. This PhD project aims to establish an integrated functional genomics platform for jumbo phage genome engineering and the systematic characterization of phage-host interactions. The project will focus on developing scalable genetic manipulation strategies to interrogate gene function in nucleus-forming jumbo phages infecting Pseudomonas species. In parallel, perturbation libraries and functional screening pipelines will be established to identify determinants involved in phage replication, intracellular compartment formation, host takeover, and evasion of bacterial defense systems. To systematically map gene essentiality and functional networks, the project will integrate high-throughput sequencing, transcriptomics, and phenotypic screening approaches with advanced microscopy-based infection assays. Particular emphasis will be placed on uncovering the roles of the large fraction of hypothetical proteins encoded by jumbo phages and identifying novel mechanisms of spatial and translational regulation during infection. By combining modern phage engineering technologies with functional genomics and molecular microbiology, this project seeks to overcome current technical barriers in jumbo phage research and provide a versatile toolkit for studying complex phage biology. Beyond advancing the fundamental understanding of phage-host interactions, the developed methodologies may contribute to future applications in synthetic biology, biotechnology, and phage therapy, where the programmable manipulation of large bacteriophage genomes is becoming increasingly important.

Project-related publications

Marino et al. 2026 Nature, Dougherty et al. 2026 Nature Microbiology, Gerovac et al. 2025 Nature, Gerovac et al. 2024 Nature Microbiology

• Group leader: Milan Gerovac
• Research group: Complexes in phage-infected cells
• Site: HZI Campus (Braunschweig)

This project investigates the cellular functions of RNA-binding proteins (RBPs) containing RNA Recognition Motifs (RRMs) in Bacteroidota, a dominant phylum of the human gut microbiota. Bacteroidota play a crucial role in maintaining gut health, but their adaptation to the harsh gut environment is not well understood. The project focuses on a family of small RRM proteins, which are prevalent in Bacteroidota and have been shown to regulate gene expression by binding to mRNAs and small regulatory RNAs (sRNAs). The research aims to elucidate the functions of these RRM proteins in different Bacteroidota species, using Bacteroides thetaiotaomicron as a model organism. Our previous study has shown that one of these proteins, RbpB, is essential for colonization of the mammalian gastrointestinal tract and regulates hundreds of mRNAs and sRNAs (Rüttiger et al., Nat Commun. 2025). However, the underlying mechanisms and generalizability to other RRM proteins and Bacteroidota members remain unclear. The current project seeks to fill gaps in understanding post-transcriptional gene expression control in gut microbiota members, potentially informing microbiota-centric therapies. The research has implications for understanding how Bacteroidota adapt to their environment and interact with other microbes, and may lead to novel strategies for manipulating the gut microbiota.

Project-related publications

Rüttiger et al., Nat Commun. 2025: DOI: 10.1038/s41467-024-55383-8

• Group leader: Alexander Westermann
• Research group: Host-Pathogen-Microbiota Interactions
• Site: Helmholtz Institute for RNA-based Infection Research (Würzburg)

Antisense technologies have the potential to form a foundation for the development of a new generation of antibiotics. Upon delivery into the bacterial cell, short antisense oligonucleotides (ASOs) or mimics thereof can directly modulate bacterial gene expression, for example, by suppressing mRNA translation of an essential target protein. The programmable nature of ASOs, which is based on simple base-pairing rules, allows rational and specific drug design and opens myriad applications including the rapid development of ASOs that can kill emerging pathogens, sensitize drug-resistant strains, or block expression of key virulence factors all while sparing the native microbiome. However, despite ample proof-of-concept for efficacy against a diverse range of bacterial pathogens in vitro and in vivo, ASOs are yet to advance to the point of drug approval. In the Vogel lab, we offer many different projects for new smart ASO applications that go beyond killing of pathogens, for example, interfering with undesired activities of commensals or enabling functional genomics of phages. This way, we are addressing the growing antimicrobial resistance crisis and providing solutions for the analysis of genetically intractable microbes.

Project-related publications

Gerovac M, Buhlmann L, Zhu Y, Ðurica-Mitić S, Rech V, Carien S, Gräfenhan T, Popella L, Vogel J (2025) Programmable antisense oligomers for phage functional genomics
Nature 646(8087):1195-1203

Sarkar P, Popella P, Pérez-Jiménez S, Vogel J (2025) RNA toehold switch-based reporter assay to assess bacterial uptake of antisense oligomers
mBio 16(4):e0398324

Vogel J, Faber F, Barquist L, Sparmann A, Popella L, Ghosh C (2025) Meeting report ASOBIOTICS 2024: an interdisciplinary symposium on antisense-based programmable RNA antibiotics
RNA 31(4):465-474

Moustafa DA, Ghosh C, Jung J, Nanayakkara A, Sapkota M, Nagamatsu K, Geller B, Vogel J, Goldberg J, Greenberg DE (2025) Developing Antisense Oligomer Biotics “asobiotics” As Precision Antibacterials: Designs, Strategies, and Considerations for Future Success
FEMS Reviews Microbiology 50:fuaf059. doi: 10.1093/femsre/fuaf059

Popella L, Jakob J, Phuong Thao D, Hayward R, Barquist L, Vogel J (2022) Comprehensive analysis of PNA-based antisense antibiotics targeting various essential genes in uropathogenic Escherichia coli
Nucleic Acids Research 50(11):6435-52

• Group leader: Jörg Vogel 
• Research group: RNA Biology of Bacterial Infections
• Site: Helmholtz Institute for RNA-based Infection Research (Würzburg)

Phages with large genomes (called jumbo phages) and complex lifestyles represent exciting opportunities to discover new molecular factors and principles of host manipulation. We are particularly interested in a certain class of jumbo phages, the “nucleus forming” jumbo phages, that hide their own genome from CRISPR/Cas and other nucleases by producing a so-called phage nucleus in the host cell. As a result, these phages must their export mRNAs into the bacterial cytosol and reimport their proteins after synthesis by cytoplasmic ribosomes. This is exciting because it follows that there must be specialised RNA transporters that one might be able to repurpose for RNA therapy. In a recent Nature paper, we published a new approach to overcoming the lack of genetics for such jumbo phages and are now using high-resolution microscopy, bacterial cell biology, and RNA biology methods to dissect the intriguing life cycle of these phages. 

Project-related publications

Gerovac M, Buhlmann L, Zhu Y, Ðurica-Mitić S, Rech V, Carien S, Gräfenhan T, Popella L, Vogel J (2025) 
Programmable antisense oligomers for phage functional genomics
Nature 646 (8087): 1195-1203

Gerovac M, Chihara K, Wicke L, Böttcher B, Lavigne R, Vogel J (2024)
Phage proteins target and co-opt host ribosomes immediately upon infection  
Nature Microbiology 9 (3): 787-800

• Group leader: Jörg Vogel
• Research group: RNA Biology of Bacterial Infections
• Site: Helmholtz Institute for RNA-based Infection Research (Würzburg)

We offer a Ph.D. position on a topic entitled ‘discovery and chemical optimization of drugs against viral infections in the immunocompromised host’. The Thesis deals with the chemical synthesis of bioactive compounds with antiviral activity. We will look at chronic viral infections in immunocompromised people, e.g. due to BK or CMV. The project is pursued in close collaboration with virologists from the German Center for Infection Research (DZIF). The primary discipline is medicinal chemistry, including multi-parameter optimization, but the candidate will also deal with chemical biology questions such as mode-of-action studies. We search for candidates with profound skill in organic synthesis and drug design. 

Project-related publications

Structure-based optimization of pyridone α-ketoamides as inhibitors of the SARS-CoV-2 main protease. Akula, Ravikumar; El Kilani, Haifa; Metzen, Alina; Roeske, Judith; Zhang, Kaixuan; Göhl, Matthias; Arisetti, Nanaji; Marsh, Graham; Maple, Hannah; Cooper, Mark; Karadogan, Burhan; Jochmans, Dirk; Neyts, Johan; Rox, Katharina; Hilgenfeld, Rolf; Brönstrup, Mark. Journal of Medicinal Chemistry (2025), 68, 2920−2941. DOI: 10.1021/acs.jmedchem.4c02172. 

Structure-based macrocyclization of α-ketoamides leads to potent inhibitors of coronaviral and enteroviral proteases Ravi Kumar Akula, …, Mark Brönstrup, under revision. 

• Group leader: Mark Brönstrup
• Research group: Chemical Biology
• Site: HZI Campus (Braunschweig)

Bacterial pathogens deploy a complex arsenal of virulence factors to manipulate host cells, yet for most of these genes we still lack a systematic understanding of how they shape the host response during infection. Classical genetic screens reveal which bacterial genes are required for survival or virulence, but they rarely capture the downstream consequences for the infected host at the resolution needed to dissect mechanism.This project aims to adapt Perturb-seq — the coupling of pooled CRISPR-based perturbations with single-cell RNA sequencing — to bacterial pathogens during active infection, and to read out the resulting host responses. Using CRISPR interference (CRISPRi) libraries targeting virulence factors, secretion systems, and regulatory genes, we will perturb the pathogen across a population of infecting bacteria. By recovering both the perturbation identity and the host transcriptome from infected cells, we will build a map linking individual bacterial genes to the specific host pathways they modulate, including innate immune signalling, cell death, and metabolic reprogramming.The work will address key technical challenges, including efficient barcode recovery from bacteria, integration of dual host–pathogen single-cell readouts, and robust assignment of host phenotypes to bacterial perturbations. The resulting dataset will provide a high-resolution, genome-scale view of how a pathogen's genetic programme is translated into host cellular outcomes.Beyond its methodological contribution, this approach has the potential to identify bacterial determinants of immune evasion and host manipulation that could serve as targets for novel anti-virulence therapies, offering a scalable framework applicable across diverse host–pathogen systems.

• Group leader: Camilla Ciolli Mattioli
• Research group: Systems Microbiology of Intracellular Pathogens
• Site: Helmholtz Institute for RNA-based Infection Research (Würzburg)

The demand for novel small-molecule drugs is on a continuous rise regarding the number of different pathologies, especially infectious diseases. Soil bacteria, and especially Myxobacteria, are a prolific source for secondary metabolites with diverse structures and intriguing biological activities. However, compared to the numbers of biosynthetic gene clusters (BGCs) predicted in the genomes of such bacteria, the number of discovered compounds is still limited. To explore the underexploited biosynthetic potential of myxobacteria and other microbial producers from the soil and human microbiota, promising strains have been whole-genome sequenced. Their predicted BGCs can be prioritized for heterologous expression based on criteria such as expected compound class and novelty, key biosynthetic genes, and BGC architectures. For discovering the matching small molecules, synthetic biology methods including recombineering and gene synthesis will be utilized. A variety of engineering- and BGC transfer strategies will be employed to improve the success rate for heterologous expression (e.g. promoter exchange or transcription regulator engineering). In a separate line of action, the activation of candidate BGCs in native strains will be pursued using genetic engineering or chemical elicitor approaches. State-of-the-art analytic methods and instrumentation at HIPS will facilitate the discovery, isolation and structure elucidation of novel compounds from new wild type and heterologous host strains. Following compound discovery, the biosynthetic pathways of isolated compounds will be elucidated by comprehensive in vivo and in vitro studies. Finally, the bioactivity of new compounds will be tested and their mode-of-action will be analyzed. The successful PhD candidate will have the opportunity to work on the following topics:
1.    Heterologous expression of BGCs from myxo- and other bacteria. 
2.    Isolation, purification, and structure elucidation of compounds produced by previously uncultured myxobacteria
3.    Characterization of the biosynthetic pathways of compounds discovered in this study. 
4.    Bioactivity testing and mode-of-action analysis of compounds discovered in this study. 
In summary, our final goal is to learn about new chemistry from nature and to produce novel compounds with improved activities based on the acquired knowledge.

Project-related publications

Autologous DNA mobilization and multiplication expedite natural products discovery from bacteria, Xie et al. (2024), Science

Discovery of the Pendulisporaceae: An extremotolerant myxobacterial family with distinct sporulation behavior and prolific specialized metabolism, Garcia et al. (2024), Chem

The Sandarazols are Cryptic and Structurally Unique Plasmid-Encoded Toxins from a Rare Myxobacterium, Panter et al. (2021) Angewandte Chemie

Bacteria as genetically programmable producers of bioactive natural products, Hug et al. (2020), Nature Reviews Chemistry

Production optimization and biosynthesis revision of corallopyronin A, a potent anti-filarial antibiotic, Pogorevc et al. (2019), Metabolic Engineering

• Group leader: Rolf Müller
• Research group: Microbial Natural Products
• Site: Helmholtz Institute for Pharmaceutical Research Saarland (Saarbrücken)

The project aims to develop small molecules tailored to be directed to their target site, i.e. bile and liver, in the context of bacterial infections. Although general concepts exist, so far, it is not known which specific properties are needed to enable compounds to reach selected target sites and how to localize compounds based on their pharmacokinetic properties. To understand and finetune pharmacokinetic properties of the small molecules, provided by a medicinal chemistry team, the successful applicant will employ cellular accumulation assays and develop transporter-based assays, such as for common drug transporters, like OATP1B1, OAT1, to investigate affinities and extend of directed transport essential for the target indication. Beside investigation of standard ADME properties, such as metabolic stability, lipophilicity, protein binding and stability in relevant physiological fluids, the successful applicant will, first, use genetic engineering methods to induce stable overexpression of drug transporters in cell lines. Next, these cell lines will be employed to establish transporter-based assays with the appropriate positive controls to investigate compound properties. Specifically, the successful applicant shall comprehensively characterize compounds regarding their substrate and inhibitory properties regarding specific drug transporters. Thereby, biochemical methods will be used to understand transporter affinities and kinetics of transport, important for design and optimization of small molecules. Further, the successful applicant will determine cellular accumulation in transporter-based and primary cell assays using mass spectrometry. Ultimately, the project will not only deliver in vitro transporter assays for pharmacokinetic characterization and compounds characterized regarding their uptake properties, but it will also develop and propose guidance for specific properties needed for target-site-directed delivery.

Project-related publications

Metzen A, Rox K. A streamlined HPLC-MS/MS workflow for rapid screening of cellular accumulation of small molecules. 2026. ChemMedChem. 21(4):e202400753. doi:10.1002/cmdc.202500753

Rox K. Exploiting PK/PD methods for optimizing and accelerating drug development of innovative anti-infectives. 2026. ChemMedChem. 21(2):e202500743. doi: 10.1002/cmdc.202500743

Rox K, Kühne A, Herrmann J, Jansen R, Hüttel S, Bernecker S, Hagos Y, Brönstrup M, Stadler M, Hesterkamp T, Müller R. Interaction of the atypical tetracyclines chelocardin and amidochelocardin with renal drug transporters. 2024. ACS Pharmacol Transl Sci. 7(7):2093-2109. doi: 10.1021/acsptsci.4c00183

Meiers J, Rox K, Titz A. Lectin-targeted prodrugs activated by Pseudomonas aeruginosa for self-destructive antibiotic release. 2022. J Med Chem. 65(20):13988-14014. doi: 10.1021/acs.jmedchem.2c01214

• Group leader: Katharina Rox
• Research group: Pharmacokinetics and Pharmacodynamics 
• Site: HZI Campus (Braunschweig)

The project aims to develop small molecules tailored to be directed to their target site, i.e. bile and liver, in the context of bacterial infections. The molecules to be developed within the context of this project act as pathoblockers, i.e. they inhibit virulence, but do not affect the bacterium itself. Therefore, the project targets to understand which dosing is necessary for a successful therapy in preclinical models and in the clinics. Moreover, it is essential to understand the necessity and the impact of backbone antibiosis on top of the pathoblocker-treatment. First, the successful candidate will develop in silico pharmacodynamic models taking into account (a) the inhibitory properties with respect to affinity and kinetics from in vitro assays toward the target enzyme as well as (b) bactericidal and bacteriostatic properties of potential backbone antibacterials using growth-kinetic in silico models based on in vitro wet lab data. Further, the successful applicant will build in silico pharmacokinetic models (compartmental and/or physiologically-based PK models) to predict pharmacokinetic behavior in preclinical species and translate the pharmacokinetic properties toward human application. For the PK models, in vitro pharmacokinetic data will be used in the sense of a bottom-up approach and later validated with in vivo data from preclinical species for selected candidate molecules. It is aimed to develop class-specific PK models to evaluate the potential for acceleration of drug development and medicinal chemistry efforts. To support this, AI methods can be used. Finally, it will be of importance to link PK and PD models to predict doses and dosing regimens needed for efficacy in preclinical models as well as in clinical trials by taking into account the distinct physiological properties from preclinical to clinical. Therefore, the different PK/PD models will probe different scenarios to select the best molecule in class. Moreover, in silico interaction studies with potential backbone antibacterials will be performed to mimic clinically realistic scenarios. Finally, the project aims to reveal PK/PD properties of pathoblockers in conjunction with backbone antibacterials to provide a pathway toward clinical development for treatment of target-site-specific bacterial infections.

Project-related publications

Rox K. Exploiting PK/PD methods for optimizing and accelerating drug development of innovative anti-infectives. 2026. ChemMedChem. 21(2):e202500743. doi: 10.1002/cmdc.202500743

Mishra S, Rox K. Effective, but safe? Physiologically based pharmacokinetic (PBPK)-modelling-based dosing study of molnupiravir for risk assessment in pediatric subpopulations. 2024. ACS Pharmacol Transl Sci. 7(12):4112-4122. doi: 10.1021/acsptsci.4c00535

Rox K, Kühne A, Herrmann J, Jansen R, Hüttel S, Bernecker S, Hagos Y, Brönstrup M, Stadler M, Hesterkamp T, Müller R. Interaction of the atypical tetracyclines chelocardin and amidochelocardin with renal drug transporters. 2024. ACS Pharmacol Transl Sci. 7(7):2093-2109. doi: 10.1021/acsptsci.4c00183

Rox K, Heyner M, Krull J, Harmrolfs K, Rinne V, Hokkanen J, Perez Vilaro G, Diez J, Müller R, Kröger A, Sugiyama Y#, Brönstrup M#. A physiologically-based pharmacokinetic/ pharmacodynamic model for treatment of Dengue infections applied to the broad-spectrum antiviral soraphen A. 2021.  ACS Pharmacol Transl Sci 4(5):1499-1513 doi: 10.1021/acsptsci.1c00078

• Group leader: Katharina Rox
• Research group: Pharmacokinetics and Pharmacodynamics 
• Site: HZI Campus (Braunschweig)

Influenza A viruses (IAVs) are zoonotic pathogens with their principal natural reservoir in wild birds. To establish infection in a new host, inhaled viruses must first traverse the respiratory mucus layer before reaching susceptible epithelial cells. However, it remains poorly understood how differences in mucus composition between host species influence viral penetration, infectivity, and host adaptation. In this project, we will investigate respiratory mucus from different human and animal sources as a potential barrier to zoonotic virus transmission. We will characterize its biochemical composition and biophysical properties, including protein/sugar content and viscosity. Using complementary virus-mucus interaction and penetration assays, we will determine how influenza viruses bind to, move through, and retain infectivity within these distinct mucus environments. By comparing viruses of human and avian origin across host-specific mucus samples, we aim to identify whether individual IAV strains are preferentially adapted to the mucus of particular host species. The project will reveal how mucus composition and physical organization shape viral mobility and infectivity before contact with epithelial cells. More broadly, this work will establish respiratory mucus as an active determinant of host restriction and cross-species transmission rather than a passive physical barrier. It will thereby contribute to a better understanding of the early events that govern zoonotic emergence and may help identify mucus-associated factors that limit or facilitate viral adaptation to new hosts.

Project-related publications

Zanin M, Baviskar P, Webster R, Webby R. The Interaction between Respiratory Pathogens and Mucus. Cell Host Microbe. 2016 Feb 10;19(2):159-68.

• Group leader: Christian Sieben
• Research group: Nano infection biology
• Site: HZI Campus (Braunschweig)

Influenza A virus (IAV) entry begins with multivalent engagement of cell-surface receptors, yet it remains unclear how viral morphology influences receptor-proximal signalling before internalisation. IAV particles can vary markedly in shape, ranging from predominantly spherical to elongated filamentous virions. These differences may alter the geometry and duration of virus-cell contacts and thereby affect receptor clustering, adaptor recruitment, and entry pathway selection. We have developed an inverted cell attachment assay that enables controlled contact between individual viruses and the plasma membrane while preventing virus entry and productive infection. Using this approach, we monitored virus-receptor interactions and the induction of clathrin-mediated endocytosis. Complementary phosphoproteomic analyses revealed distinct signalling responses downstream of activated plasma-membrane receptors. We hypothesize that spherical and filamentous IAV particles generate distinct receptor-proximal signalling outputs because their different contact geometries induce differential receptor organisation and recruitment of signalling adaptors. These differences may influence endocytic uptake and intracellular trafficking. To test this hypothesis, we will compare IAVs with predominantly spherical or filamentous morphologies. We will generate cell lines expressing fluorescently tagged signalling adaptor proteins or relevant subunits, including SH2-domain-containing proteins. After validating the expression, localisation, and functionality of these fusion proteins, we will combine the inverted cell attachment assay with quantitative live-cell imaging to measure adaptor recruitment, spatial organisation, and activation kinetics at individual virus-cell contacts. This project will determine how viral shape influences receptor organisation and signalling before entry. More broadly, it will establish particle morphology as a functional determinant of host-cell engagement and provide a mechanistic framework for understanding how virion geometry contributes to influenza virus entry and trafficking.

Project-related publications

Broich, L., Wullenkord, H., Osman, M.K. et al. Single influenza A viruses induce nanoscale cellular reprogramming at the virus-cell interface. Nat Commun 16, 3846 (2025). 2. Schlegel, J. and Sieben, C. (2026), Organizing the interface—Plasma membrane architecture and receptor dynamics in virus-cell interactions. FEBS Lett

• Group leader: Christian Sieben
• Research group: Nano infection biology
• Site: HZI Campus (Braunschweig)

Respiratory syncytial virus (RSV) remains one of the most important viral pathogens of the respiratory tract and a major cause of severe disease in infants, older adults, and immunocompromised patients. Although prophylactic antibodies and vaccines have recently improved prevention for defined risk groups, therapeutic options for established RSV infection remain limited. This project therefore addresses a highly relevant unresolved question: how does proteolytic processing of the RSV envelope proteins F and G shape the biological properties of infectious particles, including how they enter target cells, how they respond to antiviral entry inhibitors, and how stable they remain under airway-relevant conditions? The doctoral researcher will address this question using a combination of recombinant RSV genetics, quantitative entry assays, perturbation of host proteases, and infection models ranging from established cell lines to primary human airway cultures. The project is conceptually exciting because it links fundamental mechanisms of virus maturation to clinically relevant questions of antiviral susceptibility and transmission. It offers the opportunity to define how producer-cell-dependent maturation programs generate distinct RSV particle states and how these states determine infection in the next target cell. The project is embedded in the Pietschmann laboratory, which provides an outstanding environment for this work. The lab has a strong international track record in mechanistic studies of enveloped virus entry, virus-host interactions, antiviral mode of action, and viral resistance, including substantial expertise in RSV pseudotype systems, RSV entry inhibitors, and primary airway models. This combination of biological relevance, mechanistic depth, and experimental expertise makes the project highly attractive for a PhD candidate seeking rigorous training at the interface of molecular virology and translational infection research.

Project-related publications

Berg K, Haid S et al. Respiratory syncytial viral load drives ciliated cell dedifferentiation and suppresses antiviral immunity. Science Advances (2026). https://doi.org/10.1126/sciadv.aed4499

Sake SM, et al. Drug repurposing screen identifies lonafarnib as respiratory syncytial virus fusion protein inhibitor. Nature Communications (2024). DOI: 10.1038/s41467-024-45241-y.

Sake SM et al. Respiratory Syncytial Virus Two-Step Infection Screen Reveals Inhibitors of Early and Late Life Cycle Stages. Antimicrobial Agents and Chemotherapy (2023). DOI: 10.1128/aac.01055-22.

Risso-Ballester J, et al. A condensate-hardening drug blocks RSV replication in vivo. Nature (2021). https://doi.org/10.1038/s41586-021-03703-z.

Blockus S, et al. Labyrinthopeptins as virolytic inhibitors of respiratory syncytial virus cell entry. Antiviral Research (2020). DOI: 10.1016/j.antiviral.2020.104774.

Haid S, et al. Identification of a human respiratory syncytial virus (hRSV) cell entry inhibitor by using a novel lentiviral pseudotype (hRSVpp) system. Journal of Virology (2016). DOI: 10.1128/JVI.03074-15.

• Group leader: Thomas Pietschmann
• Research group: Experimental Virology
• Site: TWINCORE, Centre for Experimental and Clinical Infection Research (Hannover)

Respiratory syncytial virus (RSV) remains a major cause of acute respiratory disease in infants, older adults, and immunocompromised individuals. While recent vaccines and prophylactic antibodies have improved prevention, key determinants of RSV transmission remain poorly understood. A central unresolved question is how the physical and biochemical properties of RSV particles, together with the airway mucus environment, shape viral stability, infectivity, and airborne transmission potential. This project will investigate whether producer-cell-dependent differences in RSV virion morphology influence particle stability in respiratory fluids and aerosol-relevant environments. It will further examine whether distinct particle shapes, as well as the maturation and cleavage states of the RSV envelope proteins F and G, alter infection of physiologically relevant airway target cells. In parallel, the project will focus on the airway mucus milieu, examining how mucin composition, mucin glycosylation, and inflammation-associated changes in mucus influence RSV stability, release, and interactions with ambient air. Together, these studies aim to provide mechanistic insight into how RSV particles survive outside the producer cell and remain infectious under transmission-relevant conditions. Conceptually, this work links molecular virology, mucosal biology, and environmental exposure biology to define how RSV transmission is shaped not only by the virus itself, but also by the airway environment through which it passes. The project is embedded in the Laboratory of Transmission Immunology at the Helmholtz Centre for Infection Research, whose work integrates immunology, aerobiology, environmental virology, airway and mucosal models, in vitro and in vivo transmission approaches, and analysis of respiratory droplets and secretions. This environment provides an excellent setting for a PhD candidate seeking interdisciplinary training at the interface of respiratory virology, mucosal immunology, and airborne transmission research.

Project-related publications

Wang, C. C., Prather, K. A., Sznitman, J., Jimenez, J. L., Lakdawala, S. S., Tufekci, Z., & Marr, L. C. (2021). Airborne transmission of respiratory viruses. Science (New York, N.Y.), 373(6558), eabd9149. https://doi.org/10.1126/science.abd9149

Pastey MK, McCurdy III LH and Graham B (2025) Decoding respiratory syncytial virus morphology: distinct structural and molecular signatures of spherical and filamentous particles. Front. Cell. Infect. Microbiol. 15:1597279. doi: 10.3389/fcimb.2025.1597279

Gee YJ, Sea YL, Lal SK. Viral modulation of lipid rafts and their potential as putative antiviral targets. Rev Med Virol. 2023; 33(2): e2413

Port Julia R., Morris Dylan H,… Munster Vincent J. (2023) Host and viral determinants of airborne transmission of SARS-CoV-2 in the Syrian hamster eLife 12:RP87094 doi.org/10.7554/eLife.87094.2

• Group leader: Julia Port
• Research group: Laboratory of Transmission Immunology
• Site: HZI Campus (Braunschweig)

Mitochondria are increasingly recognized as key regulators of immune cell activation and inflammatory disease. This PhD project will investigate how genetic defects affecting mitochondrial function alter immune cell behavior in patients with mitochondrial disease, potentially increasing susceptibility to infection and contributing to chronic immune dysregulation. Working within an interdisciplinary team of scientists and clinicians in Germany (Charité, Berlin) and France (INSERM, Bordeaux), you will use cutting-edge single-cell multi-omics approaches to characterize immune cell states at high resolution.

Your role. In the PhD, you will:

• develop a new approach for parallel single-cell mtDNA genotyping and transcriptome profiling
• characterize metabolic and functional alterations in immune cells from patients with mitochondrial disease
• analyze and interpret complex datasets in collaboration with interdisciplinary partners
• help coordinate communication and exchange between collaborating teams in Germany and France

Your profile:

• Master’s degree in biology, immunology, molecular medicine, bioinformatics, or a related field
• hands-on experience in molecular biology, immunology, genomics, or computational data analysis
• strong English communication skills
• the ability to work independently as well as collaboratively in an international team

What we offer

• structured doctoral training
• an interdisciplinary and international research environment
• close collaboration with leading clinical and research partners in Germany and France
• access to advanced technologies and research infrastructure at HIRI

Project-related publication

Lesbats J, et al. (2025) Macrophages recycle phagocytosed bacteria to fuel immunometabolic responses Nature 640(8058):524-533; 

Chou CL et al. (2025) Single-cell RNA-seq using UltraMarathonRT expands the known transcriptome 2025.10.06.680646; 

Wendisch D. et al. (2021) SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis. Cell 184(26):6243-6261.e27.

• Group leader: Emmanuel Saliba
• Research group: Single-cell analysis
• Site: Helmholtz Institute for RNA-based Infection Research (Würzburg)

Macrophages are central to the immune response, yet many intracellular bacterial pathogens have evolved to survive and replicate within them. Understanding how these pathogens reprogram host cells is a major challenge in infection biology. This PhD project will investigate how intracellular bacteria manipulate macrophage functions and reshape host cell regulatory programs during infection. The project is based in the Saliba lab, which has developed a unique technology using RNA metabolic labeling to measure dynamic changes in the host cell transcriptome with exceptional temporal resolution (Toussaint et al. BioRxiv 2026; Erhard et al. Nature 2019; Erhard et al. Nature Reviews Methods Primers 2022). Building on this foundation, the PhD candidate will help establish a novel single-cell approach that combines chromatin accessibility profiling with nascent RNA measurements to capture macrophage remodeling at multiple regulatory layers. This highly innovative project sits at the interface of RNA biology, epigenomics, and infection biology, offering the opportunity to contribute to methodological development as well as fundamental biological discovery.

Your role

As a PhD candidate, you will:

• develop a new approach for parallel single-cell ATAC-seq and nascent RNA profiling
• investigate how macrophages are remodeled during intracellular bacterial infection
• analyze and interpret complex datasets in close collaboration with interdisciplinary partners
• contribute to an ambitious international research environment and present your work in scientific meetings

Your profile

You bring:

• a Master’s degree in biology, immunology, molecular medicine, bioinformatics, or a related field
• practical experience in molecular biology, genomics, immunology, or computational data analysis
• strong communication skills in English
• curiosity, initiative, and the ability to work both independently and collaboratively

What we offer

We offer:

• a cutting-edge PhD project at the forefront of infection biology and single-cell genomics
• structured doctoral training and close scientific mentoring
• an interdisciplinary and international research environment
• access to advanced technologies and excellent research infrastructure at HIRI
• strong opportunities for scientific exchange, collaboration, and career development

Project-related publications

Toussaint et al. BioRxiv 2026; Erhard et al. Nat Rev Met Primer 2022; Erhard et al. Nature 2019;

• Group leader: Emmanuel Saliba
• Research group: Single-cell analysis
• Site: Helmholtz Institute for RNA-based Infection Research (Würzburg)

Clostridioides difficile infections (CDI) are the leading cause of nosocomial gastrointestinal disorders. Primary risk factor and initiating event for CDI is antibiotic exposure which adversely affects the gut microbiota, thereby disrupting colonization resistance against C. difficile. However, the likelihood and/or severity of CDI is determined by secondary risk factors, most prominently an advanced age. So far, it remains an open question how ageing contributes to an increased susceptibility to nosocomial CDI. This knowledge gap is hampering the development of targeted prophylactic strategies. In this project, we follow the hypothesis that ageing dampens specific intestinal immune functions, such as the host-protective ILC3-IL22 axis, which increases the risk for CDI directly and/or via the microbiota. We will address the questions (1) How ageing affects host protective intestinal responses to CDI, (2) How age-related changes in intestinal immunity affect C. difficile virulence and the relative contribution of the microbiota and (3) we will explore microbiota-based interventions to prevent age-related susceptibility to CDI. The project is a tandem project with immunologists from the Charité in Berlin, and is embedded in a DFG-funded research unit focusing on dissecting protective and predisposing factors during hospital-acquired infections.

• Group leader: Franziska Faber
• Research group: RNA Biology of gram-positive Bacteria
• Site: Helmholtz Institute for RNA-based Infection research (Würzburg)