Open Positions

The research focus of the "Cellular Virology" group is localized in interdisciplinary basic research. It covers the interface between virology, immunology, RNA biology and the new, highly innovative topic of extracellular vesicles. Using both classical and self-developed methods from all these fields, we explore diverse mechanisms which activate and inhibit innate immune signaling. These innate defense processes are evolutionary conserved pathways which restrict viral replication and spread. However, innate immunity itself must also be fine-tuned to cellular requirements to prevent damage to the organism by the antiviral mechanisms themselves. In the context of the advertised position, cellular regulatory mechanisms of innate immunity will be investigated. In particular, we are investigating a previously unknown regulatory mechanism of innate immunity signaling through a naturally occurring metabolite. This mechanism is to be characterized and its effect on viral infections investigated. For more information about our group and our research, please also see our homepage.

The convergence of photons into electrochemical signals is the first step in vision. Light perception occurs in the outer segments (OS) of photoreceptor cells in the retina. The structure and function of the OS is highly regulated and dysfunction leads to blindness. In this project, we aim to understand the molecular regulation of OS formation and loss. This is key to inducing the regeneration of these light-sensitive antennae in stem cell-derived human photoreceptors and to restoring light sensitivity in a retinal degenerative disease called retinitis pigmentosa (RP). In RP, rod photoreceptors, which are important for night vision, degenerate due to rod-specific mutations. However, unaffected cone photoreceptors, which mediate high-acuity daytime and color vision, first lose their OS before they also progressively die. To date, the molecular events underlying OS loss in cone photoreceptors during and after rod degeneration are unknown. Here, we propose a systems-level survey at the transcriptomic level to reveal the molecular insults in cones. Subsequently, we will exploit the molecular players as therapeutic tools via gene therapy.

The lab of Kerstin Ludwig is offering 4 projects.

Project I - Investigating the molecular effects of genetic variants contributing to immune diseases

Despite significant advances in identifying genetic variants that contribute to immune traits and diseases, our understanding of the molecular and pathophysiological effects of these variants remains limited. Current computational algorithms used to annotate genetic variants often fall short, particularly when it comes to variants in the non-coding regions of the genome, where tissue- and cell-type-specific regulatory mechanisms are likely at play. Additionally, the rapid advancement of sequencing technologies now enables the generation of individual genome sequences at an unprecedented scale. As these technologies are increasingly applied in clinical settings, the number of genetic variants requiring accurate biological interpretation continues to grow. In this PhD project, you will investigate the functional effects of known genetic risk variants associated with selected immune phenotypes. By (i) systematically mapping base substitutions in the protein-coding regions of clinically relevant immune genes and (ii) analyzing the disease-associated variants in their non-coding regions, you will help to shed light on the genetic underpinnings of both monogenic and multifactorial types of immune diseases as well as infections. Utilizing human biomaterials and in vitro cell models, you will explore the molecular impact of these variants across the entire allelic spectrum, deepening our understanding of immune-related pathologies.

Project II - Exploring molecular variability of the immune system and its contribution to common diseases through integrative analyses of multiomics data. 

Recent advances in multiomics technologies (e.g., genomics, transcriptomics, proteomics) have unlocked new opportunities to understand the molecular complexity of the immune system. However, the role of molecular variability in shaping immune traits and its potential associations with common diseases remains largely unexplored. This PhD project will leverage systematic multiomics measurements to investigate how molecular variations in the immune system contribute to health and disease. You will integrate genetic data from genome-wide association studies and genome sequencing with data from additional various biological layers, to develop a comprehensive understanding of immune trait variability. This data-driven computational project will explore regulatory networks and pathways that govern immune responses, ultimately aiming to identify potential biomarkers for disease risk and progression. This research provides a unique opportunity to work at the intersection of immunology, genetics, and molecular biology. Using cutting-edge technologies, you will investigate how immune variability influences disease susceptibility. By collaborating with a multidisciplinary team of experts in bioinformatics, immunology, and systems biology, you will contribute to advancing personalized medicine and improving therapeutic strategies.

Project III - Genetic epidemiology of host genetics in infection and disease

As observed during the SARS-CoV-2 pandemic, there is substantial interindividual variability in phenotypes following contact with pathogens, both in the acute phase and over the long term. A portion of this variability can be attributed to differences in the host’s genetic makeup. Moreover, genetic factors underlying infection outcomes are likely to impact the host’s immune system, potentially contributing to other non-infectious diseases. In this project, we will employ genetic epidemiology approaches to identify genetic factors associated with infection outcomes and their relationships with various dimensions of common diseases. By leveraging large biomedical databanks, such as the UKBiobank and Allof Us, we will analyze cohort-level data to uncover genetic contributions to disease progression following infections and the associated health risks mediated by these infections. As a PhD candidate, you will engage in comprehensive data analysis of large datasets, utilizing advanced statistical methods and bioinformatics tools to investigate how host genetic variations influence responses to infections. You will explore the relationships between genetic factors and disease trajectories, contributing to our understanding of susceptibility and resilience in the face of infectious agents. This research presents a unique opportunity to work at the forefront of genetic epidemiology, collaborating with a multidisciplinary team of researchers specializing in genetics, epidemiology, immunology, and infectious diseases. We welcome motivated candidates with a strong background in epidemiology, statistics, or related fields to apply for this position.

Project IV

The Ludwig and the Paeschke lab search jointly for two PhD students.

Genomes can form non-canonical (non-B) DNA structures such as guanine quadruplexes (G4). These have been shown to carry biological information beyond the primary sequence and are often located in non-coding regions of the genome. In humans, genetic variants in non-coding regions have been identified as contributors to many multifactorial diseases, and are hypothesized to mediate their effects via modifications to cell-type specific gene expression programs. This collaborative project aims at dissecting the contribution of genetic variation in G4 structures to human trait variation and disease. The project will employ an interdisciplinary approach combining human genetics and molecular biology/biochemistry. Large-scale genetic datasets, including summary statistics from genome-wide association studies (GWAS), will be analyzed to determine if risk variants are enriched within sequences capable of forming G4s. Selected findings will be confirmed at the molecular level, by analyzing downstream effects in cellulo and investigating how, whether individually or as part of multi-variant haplotypes, they affect G4 formation and stability, and how this impacts protein binding. This project is a tandem project which will train two students in complementary research areas, bridging the gap between computational biologists and molecular biochemists. PhD1 will primarily perform the computational work integrating sequences with the potential to form G4s with large-scale systematic genetic and functional data sets. The successful candidate is expected to have a background in life science informatics, bioinformatics, computational biology and/or data science. PhD2 will perform most wet lab experiments and, therefore, should have a background in either molecular biology or cell biology. If you are interested in applying for this project, please indicate your preference (PhD1 or PhD2).

The Ludwig and the Paeschke lab search jointly for two PhD students.

Genomes can form non-canonical (non-B) DNA structures such as guanine quadruplexes (G4). These have been shown to carry biological information beyond the primary sequence and are often located in non-coding regions of the genome. In humans, genetic variants in non-coding regions have been identified as contributors to many multifactorial diseases, and are hypothesized to mediate their effects via modifications to cell-type specific gene expression programs. This collaborative project aims at dissecting the contribution of genetic variation in G4 structures to human trait variation and disease. The project will employ an interdisciplinary approach combining human genetics and molecular biology/biochemistry. Large-scale genetic datasets, including summary statistics from genome-wide association studies (GWAS), will be analyzed to determine if risk variants are enriched within sequences capable of forming G4s. Selected findings will be confirmed at the molecular level, by analyzing downstream effects in cellulo and investigating how, whether individually or as part of multi-variant haplotypes, they affect G4 formation and stability, and how this impacts protein binding. This project is a tandem project which will train two students in complementary research areas, bridging the gap between computational biologists and molecular biochemists. PhD1 will primarily perform the computational work integrating sequences with the potential to form G4s with large-scale systematic genetic and functional data sets. The successful candidate is expected to have a background in life science informatics, bioinformatics, computational biology and/or data science. PhD2 will perform most wet lab experiments and, therefore, should have a background in either molecular biology or cell biology. If you are interested in applying for this project, please indicate your preference (PhD1 or PhD2).

Our research focus lies in the field of musculoskeletal immunology. The overall goal is to understand the cellular and molecular mechanisms of musculoskeletal immune responses to develop novel immunology-centered diagnostic and therapeutic options to better predict and treat musculoskeletal pathologies. Specifically, our current studies investigate immune responses in the context of implants and during bone homeostasis.

We are seeking a highly motivated, team-oriented PhD student to conduct research on aspects of osteo- and trauma immunology. The candidate will combine cellular and molecular immunology techniques with in vivo disease models and patient-derived samples to dissect the underlying mechanisms of the communication between immune system and musculoskeletal apparatus. The PhD student will be integrated into the local graduate program BIGS Immunosciences and Infection with outstanding training opportunities in multidisciplinary, interconnected scientific fields and will be supported by additional mentoring and networking opportunities.

Obesity is an epidemic of global concern, with nearly half of all adults being overweight. Western diet, rich in fat and lipids and poor in aryl hydrocarbon receptor (AHR) ligands, acts on the adipose tissue and affects cellular programming and cellular communication. Eosinophils, through effects on other immune and stromal populations, are key players in adipose tissue physiology and counteract diet-induced metaflammation. Adipose tissue eosinophils have a distinct transcriptional signature when compared to blood eosinophils or those from other tissues, but which transcription factors control adipose tissue eosinophil functions has not been determined. Our previous work demonstrated that eosinophils adapt to the local tissue environment and this adaptation to the intestine is partially controlled by the transcription factor AHR, which regulates a range of eosinophil functions (Diny et al., J Exp Med 2022). This project aims to uncover how dietary regulation of AHR affects adipose tissue eosinophil function and thereby the response to diet-induced obesity.

B cell Immunology / Mucosal Immunology

Our body sites are populated by a diverse community of microbes, the microbiota. Secretory Immunoglobulin A (SIgA) antibodies on our mucosal surfaces neutralize pathogens and regulate our microbiota. In intestinal immunity, SIgA has a dual role. Despite immune exclusion of pathogens, SIgA facilitates retro-transcytosis of luminal antigens to promote specific IgA induction. However, the impact of constant SIgA-mediated antigen sampling on intestinal B cell immunity and the microbiota remains unknown. To address this, we use a variety of immunological and microbiological methods. This includes but is not limited to germ-free and gnotobiotic model systems, flow cytometry, in vitro binding assays, single B cell sequencing and monoclonal antibody generation. This project aims to decipher SIgA's potential to boost gut immunity to design effective mucosal vaccines and promote gut health

The lab of Kaan Boztug is offering 2 projects

The Boztug lab at the University Hospital Bonn has a focus on deciphering the molecular origin of inborn errors of immunity and is integrated with the Excellence Cluster ImmunoSensation². Prof. Kaan Boztug is the newly recruited Clinical Director of the Department of Pediatric Immunology and Rheumatology at the University Hospital of Bonn and PI of an ERC Consolidator grant (iDysChart), integrating basic research into mechanisms of immune dysregulation and clinical translation.

Project I - Investigating the molecular basis of autoimmunity and autoinflammation in inborn errors of immunity with aberrant actin dynamics

We invite highly qualified candidates for a PhD position to investigate the molecular mechanisms underlying autoimmunity and autoinflammation in actin-mediated immune defects. In previous work from our lab, we have identified novel immune-mediated actinopathies including HEM1 deficiency or DOCK11 deficiency and deciphered the underlying molecular pathomechanisms (see Salzer E et al., Science Immunol 2020; Block et al., New Engl J Med 2023). 

For this project, we will investigate the cellular and molecular defects arising from a genetic variants affecting actin-regulatory proteins, including novel disease-causing genes. We will decipher the differential effects of immune actinopathies on immune cell development and function, and compare the (epi)genetic profiles characteristic of individual genetic defects. These studies will be complemented by modeling disease mechanisms in suitable cell line and zebrafish model systems. 

Project II - Investigating the molecular basis of autoimmunity and autoinflammation in inborn errors of immunity with aberrant actin dynamics

We invite highly qualified candidates for a PhD position to investigate the molecular mechanisms in a novel type of combined immunodeficiency affecting both T- and B-cell development and function. In previous work from our lab, we have successfully deciphered underlying disease mechanisms in other combined immunodeficiencies (see Shahin T et al., Science Immunol 2021; Block et al., New Engl J Med 2023; Köstel Bal et al., Blood 2023). 

For this project, we will investigate the molecular mechanisms underlying aberrant T- and B-cell development including defective stromal cell interaction and compare molecular signaling defects and profiles using single-cell RNA sequencing to known genetic etiology of combined immunodeficiency. We will dissect underlying mechanisms of autoimmunity and autoinflammation such as defective T- and B-cell receptor signaling and excessive inflammasome activation. Based on our findings, we will also consider the potential for therapeutic intervention, supported by both CRISPR- and chemosensitivity screening.

In the Liedmann lab our research is focused on generation-spanning immune regulation. How does the environment influence the epigenetic landscape of our germ cells? How are changes to the epigenetic landscape transmitted through generations? And how does that shape the immunity of our children and grandchildren? Questions like these are driving our work. To answer those questions, we utilize human and mouse germ cells, in vivo model systems, and state of the art sequencing technologies.
 

We are looking for candidates with

• a strong motivation to work in the field of environmental immunology
• a master’s degree or equivalent
• a background in immunology, epigenetics, or a related field
• the ability to work with in vivo models
• a collaborative attitude and ability to work both independently and in a team
• very good English skills