EXC 306: Inflammation at Interfaces

Inflammation at barrier organs (skin, lung, gut) is a central medical problem including many civilisation diseases such as asthma and chronic inflammatory bowel disease. The vision of the cluster of excellence is that barrier problems may be causally involved in many other systemic inflammatory (e.g. coronary heart disease) and malignant (e.g. colorectal carcinoma) disorders.
To improve the multidisciplinary study of barrier disorders, the cluster of excellence will restructure research at five faculties at the universities of Kiel and Lübeck and the Research Center Borstel, Leibniz-Center for Medicine and Biosciences. Twenty-nine principal investigators and 108 additional excellent scientists have established five content- and method-defined research areas by joining their individual research operations, which together will streamline the scientific processes of the investigation of diseases from genomic discovery to model-system based mechanistic understanding and its validation at the patient level. This leads to a new quality of multidisciplinary research translating a synergistic generation of knowledge around etiologically relevant molecule families into application in inflammatory barrier diseases and their treatment.
The research environment forms the basis of an innovative concept of interdepartmental postgraduate education (medicine/life sciences). The applicant institutions have committed to the inauguration of 21 new professorships and departments to complement and strengthen the research environment. The multidisciplinary structure of the cluster of excellence provides the scientific environment for twelve new independent junior research groups ensuring early independence and promoting gender-equality of young scientists. Finally, the establishment of a clinical "Comprehensive Center for Inflammation Medicine" (CCIM) ensures a permanent, multidisciplinary integration between different clinical sub-disciplines and basic research; in addition it facilitates the cooperation with industry.

Chronic Inflammatory Barrier Diseases (CIBD) emerged as an increasing challenge due to their systemic biological effects on the organism and the complex interaction between genetic and environmental factors. In the Cluster’s first funding period (FP-1), the hypothetical disease model led the research process in a linear fashion from a few anticipated disease gene identifications to structure, evolutionary and functional annotation and exploration in patients. However, the unprecedented complexity and breadth of etiologic findings prompted a different approach in the second funding period (FP-2), in which our research strategy was developed further with Research Areas (RA) investigating in-depth key genetic, genomic and functional elements of inflammatory diseases while interacting with Cluster Laboratories (CL). The Cluster “Inflammation at Interfaces” combined the expertise and (inter-)national collaborations of a unique multidisciplinary team of >250 scientists from ten disciplines to drive the research of CIBD. A major achievement of the last decade is a profound change in the scientific culture and governance at all participating institutions/faculties, which has contributed to a significant increase in scientific productivity and visibility. Our local development is unique in its combination of disciplines and its strong concentration on clinical translation. This comprises a critical mass in interdisciplinary patient access across the entire field of CIBD, including re-organization of care for inflammation patients from different subspecialties in Comprehensive Centers for Inflammation Medicine (CCIM). This supports large cohort studies and therapeutic trials. The interdisciplinary research culture that resulted from this structural innovation has led to an outstanding series of high-impact findings. For example, Cluster scientists have led or contributed to many published international genetic meta-analyses and GWAS analyses for CIBD entities. Another developmental highlight of this Cluster was the development of an IL-6 trans-signaling inhibitor, which is currently being tested in a phase 2 trial for a CIBD. Our ongoing Cluster “Precision Medicine in Chronic Inflammation” (PMI) is based on the achievements of the previous Cluster and aims to describe an individual molecular efficacy signature for therapies in patients and will prompt individual choices of anti-inflammatory therapies in the future. The setup of a medical systems biology and a massive investment in IT were important pre-requirements and achievements of the FP-2. The ultimate goal of the new Cluster PMI is to define inflammatory barrier disease at early, not yet clinical, stages once it has reached a point-of-no-return and to develop rational interventions which intercept the further course.