Open PhD Project
The following PhD projects are available in 2026 (earliest possible start in May 2026)
The epithelial cells of the gastrointestinal (GI) tract are in constant contact with microbial products and have to balance tolerance of commensals and defense against pathogens. To sense the microbial world, epithelial cells are equipped with innate immune receptors, such as toll-like receptors or inflammasomes. Our group uses adult stem cell derived organoids to better understand epithelial innate immunity and the host response to infection. Organoids are 3-dimensional, primary cell cultures. Analyzing human and murine GI organoids, we found that innate immune receptor expression is highly organized in the GI tract: Each segment of the GI tract expresses a specific set of innate immune receptors. We now wonder, how this spatial organization develops and how this impacts the defense against pathogens. In this project, we will use CRISPR/Cas9-mediated genetic modification of human GI organoids to analyze the impact of specific genes on innate immune receptor expression. We will further use infection models, such as EPEC infection of human intestinal organoids, to better understand the importance of innate immune recognition in infection.
References:
DOI: 10.1136/gutjnl-2019-319919
DOI: 10.1016/j.ydbio.2016.09.014
Innate lymphoid cells (ILCs) are tissue-resident lymphocytes that play a critical role not only in immunity to infection but also in maintaining and regulating tissue homeostasis. Our recent work has demonstrated that ILCs support nutrient uptake in the small intestine and that alterations in their effector programs can profoundly influence systemic metabolism (Gronke, Nature 2019; Guendel, Immunity 2020; Diefenbach, Immunity 2020).
In this project, we aim to explore the role of group 3 ILCs (ILC3) and their effector molecules in mediating metabolic adaptation during pregnancy. Pregnancy represents one of the most metabolically demanding physiological states, resembling a naturally occurring form of metabolic syndrome. However, the contribution of immune components—and of ILCs in particular—to the organism’s adaptation to these metabolic challenges remains largely unknown.
Our preliminary data suggest that pregnancy induces intestinal growth, leading to an increase in enterocyte numbers that enhance nutrient absorption. Strikingly, mice lacking ILC3 exhibit impaired intestinal growth and reduced nutrient uptake, which correlate with lower birth weights in their offspring. Moreover, offspring from mothers with impaired intestinal adaptation during pregnancy display, as adults, increased susceptibility to inflammatory and metabolic disorders.
Building on these findings, this project will address three specific aims:
- Mechanistic memory: Determine how suboptimal metabolic “experience” during pregnancy and lactation is “stored” in the immune system and in tissues.
- Metabolic profiling: Characterize in detail the metabolic alterations in offspring from control vs. ILC3-deficient mothers.
- Therapeutic exploration: Assess whether these pathways can be modulated to enhance resilience to inflammatory and metabolic diseases.
Through these studies, we aim to uncover fundamental principles of immune–metabolic crosstalk during pregnancy and identify novel pathways that support maternal and offspring health.
Funding: ERC AdvG, DFG
Most cells in our bodies contain two copies of each autosomal gene, one inherited from our mother, and one from our father. Interestingly, evidence over the last 30 years has shown that our gene copies (alleles) are not equally used, and especially immune response genes, can display an allelic bias or exclusion. Using primary patient samples and murine models, this project aims to resolve the contribution of variable allele usage to the inflammatory response and pathogen detection, and seeks to understand how transcriptional variability couples with genetic diversity to alter innate immune cell population dynamics and host defense.
We have recently shown through DBLalpha tag analyses that asymptomatic, dry-season infections express fewer and lower levels of the var genes compared to clinical wet-season cases (Ceesay a& Kampmann 2025). This restricted profile of variant surface antigens (VSAs) suggests an immune evasion strategy, allowing parasites to persist at low levels by avoiding antibody recognition and minimizing cytoadhesion. Now, we will use single-cell and bulk RNAseq to define complete transcriptional landscape of P. falciparum in persistent infections. We will track parasites from individuals infected from the wet into the dry season and interrogate VSA expression, var gene switching, and potential total loss of var expression, compared to acute clinical cases. Host humoral and inflammatory response will be integrated to fully elucidate the molecular mechanism promoting longer circulation of iRBCs in dry season asymptomatic infections (Andradre 2020), and reveal P. falciparum immune evasion strategies.
NK cells are innate lymphocytes that play critical roles in immune defense against viral infections and cancer. Despite being regulated by germline-encoded receptors, NK cells can undergo clonal expansion and epigenetic remodeling, acquiring memory-like properties that enhance their responsiveness to specific stimuli—particularly following infection with cytomegalovirus (CMV). Our recent findings reveal the long-term persistence of highly expanded CMV-specific NK cell clones carrying somatic mutations. These mutations are enriched in cancer driver genes and immune-related pathways, suggesting functional consequences that may contribute to clonal selection and persistence. This challenges the conventional view of NK cell regulation and introduces somatic genetic variability as a novel mechanism influencing immune cell fitness. The goal of this project is to investigate the molecular and functional consequences of selected somatic mutations on NK cell proliferation, survival, and effector functions. Through a combination of genetic perturbation, genomics, and cellular assays, we aim to elucidate how these variants contribute to NK cell clonal expansion and long-term memory, and how they may enhance antiviral responses. These studies will advance our understanding of NK cell memory formation and could inform novel strategies to optimize NK cell-based immunotherapies for infection and cancer.
References:
Rückert T, […], and Romagnani C, Nat Immunol 2022
Hammer Q, Rückert T,.. and Romagnani C, Nat Immunol 2018a
Hammer Q, Rückert T and Romagnani C, Nat Immunol 2018b
Immunological memory enables the immune system to adapt to pathogen encounters, leading to enhanced functionality and protection against reinfection. Mechanistically, memory formation involves shifts in immune receptor repertoires through clonal expansion of antigen-specific cells, accompanied by extensive epigenetic, transcriptional, and metabolic rewiring. These processes generate long-lived memory populations capable of mounting rapid and potent recall responses.
While the mechanisms driving memory formation in the adaptive immune system are well defined, recent discoveries of memory-like behavior in innate immune cells raise fundamental questions about the similarities and differences between primary and recall responses in the innate immune system.
In the Romagnani lab, we study Natural Killer (NK) cell responses to Cytomegalovirus (CMV) infection, which induce the clonal expansion of “adaptive” NK cells resembling classical immune memory. This PhD project will use in vitro models to investigate primary and recall responses of human CMV-specific NK cells, combining functional assays, flow cytometry, single-cell genomics, and gene editing. These approaches will elucidate the receptor requirements, response kinetics, and gene-regulatory networks that shape CMV-specific NK cell behavior.
The PhD candidate will build on established experimental pipelines and extensive preliminary datasets, integrating wet-lab and computational methods. The ultimate goal is to develop a quantitative understanding of how receptor stimulation and cellular states are integrated over time to orchestrate NK cell effector responses — thereby identifying novel molecular checkpoints that could inform improved NK cell-based immunotherapies.
References:
Rückert T, […], and Romagnani C, Nat Immunol 2022
Hammer Q, Rückert T,.. and Romagnani C, Nat Immunol 2018a
Hammer Q, Rückert T and Romagnani C, Nat Immunol 2018b