Prof. Irmgard Förster, LIMES Institute Bonn
Importance of chemosensing receptors for intestinal immune homeostasis
The intestinal immune system represents the largest reservoir of immune cells in the body and is constantly exposed to antigenic challenges via dietary constituents, commensals and pathogens. Besides protein antigens, lipids and fibre, low molecular weight metabolites and environmental or food-derived chemicals exert important influences on the regulation of immunity. Such chemicals are recognized by various types of chemosensing receptors, such as the ligand-activated transcription factor Aryl hydrocarbon receptor (AhR), G-protein coupled receptors and nuclear hormone receptors. We are specifically interested in the function of the AhR and its regulator AhR repressor (AhRR), as well as gpr84, that both share the ligand 3,3'-diindolylmethane, a derivative of glucobrassicin found in green vegetables. In addition, the AhR, pregnane X receptor (PXR) and constitutive androstane receptor (CAR) appear to cross-regulate each other and thereby may jointly regulate immune functions in the intestine. The project will involve the generation of multi-gene knockout mouse models using Crispr/Cas technology and the application of multi-color flow cytometry for immune phenotyping. In addition, we will perform dietary intervention studies, functional assessment of intestinal barrier function using colitis models, as well as studies on neuro-immune crosstalk. The impact of the chemosensing receptors on gene expression in immune cells will be investigated by global transcriptome and epigenetic analyses.
Prof. Veronika Lukacs-Kornek, Institute of Experimental Immunologie (IEI)
Prof. Dr. Lukacs-Kornek and her team are focusing to determine the role and impact of stromal cells on immunregulation during priming in secondary lymphoid organs and within the tumor microenvironment. Stromal cell biology is an emerging field that investigates how these non-hematopoetic cells contribute to disease development. The PhD candidate will contribute in a research project that focuses on stroma-immune cell cross-talk in the tumor milieu. The applied techniques involve flow cytometry, working with in vivo animal models involving cell culture and confocal/intravital microscopy analyses. The candidate will learn various immunological assays to address the function of stromal cells and will use genomic analyses to address the various subpopulations within and outside of the tumor environment.
Prof. Katrin Paeschke, Medical Clinic III
The research group is interested in understanding the impact of secondary G-rich structures for immune response. In detail. In recent year it has been shown that G-rich regions can fold into G-quadruplex DNA or RNA structures. Due to their stability, location and evolutionary conservation these structures can influence DNA replication, transcription and DNA repair events. Due to their stability a tight regulation of G4 formation and unfolding is essential to preserve genome stability. In recent years it is clear that changes in genome stability have a huge impact on immune response. In the project, he/she will shed light on G4 mediated genome instability and how these structures are sensed by the immune pathway. He/She will use different genome wide, biochemical and molecular biological techniques in human tissue culture cells. See Paeschke et al 2011 Cell, Paeschke et al 2013 Nature, Wanzek et al 2017 NAR or Sauer Nat Comm 2019 for more information on the work in the Paeschke lab (www.paeschkelab.de).
Prof. Alexander Pfeifer, Institute of Pharmacology and Toxicology
Obesity has become a worldwide threat to the public health and efficient treatments are urgently needed. Obesity is characterized by an unhealthy increase in adipose tissue, due to hypertrophy and hyperplasia of adipocytes. In addition, during development of obesity inflammatory processes are involved as observed by massive influx of immune cells, e.g. myeloid cells, into adipose tissue. This inflammatory state of adipose tissue affects also other organs and results in obesity associated co-morbidities like insulin resistance, cardiovascular disease, and diabetes (Sanyal et al., 2017). Two types of adipose tissue do exist, white adipose tissue (WAT) and brown adipose tissue (BAT) (Pfeifer and Hoffmann, 2015). Whereas WAT is mostly considered to be the main storage for body fat, BAT is characterized as specialized fat tissue that is able to dissipate energy as heat. This metabolically active adipose tissue has been discovered in adult humans and it is considered as an attractive target for developing anti-obesity therapies (Gnad et al., 2014). Brown-like fat cells were also identified within WAT and contribute to energy expenditure (Hoffmann et al., 2015; Mitschke et al., 2013). In obesity, BAT function is impaired and its phenotype switches to WAT. Within this project we would like to investigate the role of different immune cell subsets especially in BAT and WAT function and plasticity.
Dr. Florian Schmidt, Institute of Innate Immunity
The research group of Florian I. Schmidt seeks to uncover how the appropriate inflammatory response against pathogens and other signatures of danger is achieved at the cellular and molecular level. This requires exquisite sensitivity, but also measures to prevent false alarms and to downmodulate inflammatory responses.We have generated cellular biosensors to detect inflammasome and interferon responses and apply them to understand the inflammatory responses to viruses in a comparative manner, focusing on fundamental cellular processes rather than specific virus families. We have also begun to investigate cellular control mechanisms to contain or end inflammatory processes, which are to date only poorly understood.In order to gain novel insights, we heavily invest in novel technologies with a focus on strategies to manipulate cellular processes in human (primary) cells. To do so, we are in the process of developing a comprehensive collection of custom-made alpaca single domain antibodies (nanobodies or VHHs), which we will use to perturb, visualize and ultimately understand immunological signaling cascades in the responding cell types at endogenous protein levels.
Prof. Sven Wehner, Department of Surgery
Our group is interested in the contribution of peripheral neuroimmune pathways in the biology of intestinal and pancreatic disorders. Enteric glial cells, specialized cells of the enteric nervous system, have been identified by us and others to play an important immunomodulatory role in intestinal homeostasis. During inflammation, glial cells undergo phenotypical changes and can either promote or suppress inflammation. Importantly, increased numbers of glial cells have been observed in developing adenocarcinomas of the colon and pancreas, suggesting that these cells play a prominent role in tumor development and progression. The mechanisms of this are, however, poorly understood. In this PhD project we will investigate the role of glial cells in intestinal and pancreatic tumor formation. In vitro studies including cultures of primary glial cells and cancer cell lines and in vivo animal models of colon and pancreatic cancer will help us understand the role of glial cells in the biology of these diseases. Collaborations with international partners in Amsterdam will allow us to address the role of the microbiome in glial cell biology in homeostasis and cancer. The optimal candidate has an expertise in (primary) cell culture techniques and animal disease models. Further expertise in flow cytometry and fluorescence microscopy are of advantage but not required. We offer a position in a growing international team of medical and basic scientists. A lab rotation to our Dutch collaborator (AMC, Amsterdam) can be part of the PhD training.
Prof. Christoph Wilhelm, Institue of Clinical Chemistry and Clinical Pharmacology
The work is focused on understanding aspects of the dietary regulation of the immune system. In particular the project includes the investigation of how diets (e.g. ketogenic diets) and dietary components drive or prevent chronic inflammation and the metabolic pathways important for the activation of innate lymphoid cells (ILC) in heath and disease. The overall aim is to identify dietary interventions strategies to treat chronic inflammatory conditions such as asthma, inflammatory bowl disease or psoriasis. We seek for candidates with strong background in cellular immunology, molecular cell biology or biochemistry.