Schwerpunkt

1. Signalling pathways in inflammatory bowel disease (IBD)
Staff: Ana Mandic, Julien Verdier, Silvia Roubrocks
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal system of unknown aetiology that affects patients of all age groups including children. Intracellular signalling pathways such the NF-κB and MAP-kinase pathways are master regulators of inflammation but also of cellular development and survival. A balanced activation of these pathways seems to be important to maintain homeostasis in the gastrointestinal tract and experimental studies and data from patients suggest that NF-κB and MAP-kinase pathways are dysregulated in the course of IBD.

Using animal and cell culture models, we are currently studying the role of C-June N-terminal kinases (JNK) in IBD. Furthermore, we are part of a collaborative research initiative that aims at revealing oscillating biological processes such as the NF-κB pathway associated with IBD by applying a systems medicine approach. The international SysmedIBD consortium led by Werner Müller, Manchester consists of mathematicians, systems biologists, geneticists, molecular and cellular biologists, immunologists and clinicians. The objective of the project in Aachen together with clinical centres at the Universities of Maastricht and Liverpool is to link the basic research, mathematical modelling and discovery of small molecules back to the clinical situation of IBD patients. The aim of these projects is to define new treatment targets and biomarkers that may predict the disease’s course and the outcome of treatment.

 

2. Development of glycan-functionalized microgels for specific binding of Clostridium difficiletoxins
Staff: Silvia Roubrocks, Ana Mandic
The project funded by the SFB 985 combines expertise from polymer chemistry (Alexander Kühne, DWI, RWTH Aachen), glycobiotechnology (Lothar Elling, Helmholtz-Institute, RWTH Aachen), and biomedical science (our group, external collaborator Ralf Gerhard, MH Hannover) with the goal of developing a novel non-antibiotic therapy for Clostridium difficile (C. difficile) associated disease (CDAD), a disorder that represents a worldwide increasing health problem.

3. Recognition of intestinal food and microbial antigens by the adaptive immune system during homeostasis and inflammation
Staff: Eveline Bennek, Lisa Frehn, Anke Jansen, Teresa Langen
Collaborators: Thomas Kufer, Uniklinik Köln; IngaBenz / Alexander Schmidt, Uni Münster; Claude Parsot / Phillippe Sansonetti, Institut Pasteur, Paris; Gerda Wurpts / Stefani Röseler,Hautklinik, UKA

The immune system of the gastrointestinal tract in confronted with an enormous amount of potentially harmful antigens derived from food and the microbiotic flora. During homeostasis intestinal antigens trigger mainly a tolerogenic immune response, whereas in the course of an infection with a pathogen proinflammatory effect or responses are induced and required for pathogen clearance. Dysregulated immune responses to the microbiotic flora and food are found in patients with inflammatory bowel disease and food allergy, respectively.
We are aiming to understand the differential potency of food antigens that are present assoluble proteins and microbial-derived antigens that are associated with proinflammatory molecules such as bacterial cell wall components (e.g. LPS or peptidoglycans) to induce T and B cell responses in the gastrointestinal tract.
To this end, we are analysing serum and stool antibody levels against food and floral antigens in IBD and food allergy patients as well as in controls. Furthermore, we are using animal models to study the intestinal immune response to model antigens either in soluble form or expressed in different compartments of a non-pathogenic Escherichia coliduring homeostasis and intestinal inflammation.
The objective of the project is to further understand the mechanisms that underlie tolerance versus effector responses induced by luminal antigens and, thus, to define new therapeutic strategies for IBD and food allergy.