Persönlicher Status und Werkzeuge

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Research Program of the GRK 1482

A key hypothesis of the GRK 1482 is that nutritional components (high fat diet, dietary lipid composition, iron) and luminal bacteria (derived from fermented food and inherent gut microbiota) modulate a highly interactive network of cells (epithelial, immune and nerve cells) and mediators (hormones and metabolic intermediates) in the gut.

A careful evaluation of the first generation of PhD projects based on the publication output and the research potential for future development was used to guide the selection process for the future research program.

Research projects of the 1st PhD generation successfully established molecular mechanisms of microbe-host interactions in infectious and IBD-related animal models. Specifically lactobacilli and enterococci served as model organisms to identify bacterial structures that mediate beneficial or deleterious effects in the disease-susceptible host. As a consequence, we further focus on commensal bacteria to characterize the molecular mechanisms of microbe-host interaction (blue labelled projects). A first step to implement metagenomic tools in studying the complex gut microbial ecosystem was integrated as a new angle towards the GRK theme of microbe-host interactions. In addition to microbes, we decided to emphasize on iron as an additional luminal factor with great relevance in human nutrition and IBD. Parallel to research axis of microbe-inflammation-immune function, the second major line of research within the GRK highlights the role of the gut interface as a sensing and signaling organ for metabolic dysfunctions. Thus, projects labelled green (epithelial) and orange (subepithelial) will address the role of epithelial-derived inflammatory signals on metabolic pathologies, bile acids on brown adipocyte differentiation and energy expenditure, as well as effects of enteric endocrine signals on melanocortinergic circuits in the enteric nervous system and the brain. Finally, human studies on the genetic and molecular basis of fructose-intolerance as well as angiotensin and RANTES effects on gut hormone secretion relate to the effort to move basic science into human translation.

A unique technology and research model platform: The research consortium compiles a unique list of methodologies at the level of molecular and cellular technologies as well as a variety of animal models in the research areas of IBD as well as diet-induced obesity and metabolic dysregulations. A variety of new cutting-edge technologies are availabe within the next generation of GRK including a new germfree mouse facility for gnotobiotic experiments, a mouse metabolic phenotyping unit and sequencing facilities. Together with capturing and imaging techniques including laser dissection and confocal microscopy, luminescent reporter gene imaging in mice (Xenogen-LUX-Camera system) and fast neuro-imaging the GRK is fully equipped to study cellular mechanisms in model systems with different levels of complexity (cultured cell, nematode, mouse), as well as in humans.