SFB 1449:  Dynamic Hydrogels at Biointerfaces

Subject Area Chemistry
Biology
Medicine
Term since 2021
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 431232613
 

Project Description

The overarching goal of CRC 1449 is to investigate the key physicochemical parameters that determine protective hydrogel function at biological interfaces in health and define abnormalities in disease for the prospective development of novel therapeutic strategies. We focus on the individual and combined contributions of hydrogel components and their functional impact on airway and intestinal surfaces, which constitute the largest biointerfaces of the human body that are covered by hydrogels. In this context, we will include studies of exemplary pulmonary and gastrointestinal diseases, in which abnormal hydrogels play a central role or have been implicated as important determinants of pathogenesis. These examples include i) cystic fibrosis (mucoviscidosis) as a chronic muco-obstructive lung disease triggered by abnormal viscoelastic properties of mucus in the airways; ii) acute respiratory tract infections caused by bacteria and viruses; and iii) inflammatory bowel disease, a chronic disease condition associated with abnormal mucus composition in the gastrointestinal tract. Our overarching approach will determine mucus properties and dynamics at the molecular level including structure, mesh size, charge conditions, viscoelastic and transport behavior, to determine which molecular and functional parameters determine healthy versus disease states. The three main research objectives of the CRC 1449 are: 1. To determine the role of individual hydrogel components, i.e. biomacromolecules, salt and water, in the complex process of hydrogel formation and its structure and function at biointerfaces. 2. To reconstitute synthetic mimics of native hydrogel components and study whether the synthetic hydrogel variants can replicate the native barrier to prevent infection by bacteria and viruses. 3. To define the role of hydrogel properties (mucus/glycocalyx) in health vs. disease and to design new therapeutic concepts to improve hydrogel function, such as new mucus crosslinkers or mucolytics. We are convinced that only a transdisciplinary approach based on expertise in physics, chemistry, material sciences, biology, and medicine that is integrated with frontline modeling approaches will allow the much-needed comprehensive investigations of the complex and dynamic hydrogel networks at biointerfaces of the airways and intestine. The CRC 1449 is driven by biomedical questions with a long-term and increasingly translational perspective throughout three funding periods: (1) understanding the structure, properties and dynamics of hydrogels at biointerfaces (2) dynamic behavior and modeling of native vs. synthetic hydrogels; definition of the barrier function of the mucus and the glycocalyx, as well as the interaction of interfacial layers (3) overcoming barrier dysfunction to prevent infection and inflammation by synthetic mucus-mimetics and therapeutic targeting of mucus (dys)function by mucus modulating agents.
DFG Programme Collaborative Research Centres

Current projects

Applicant Institution Freie Universität Berlin
Participating University Charité - Universitätsmedizin Berlin; Humboldt-Universität zu Berlin; Technische Universität Berlin
Participating Institution Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP)
im Forschungsverbund Berlin e.V.; Max-Delbrück-Centrum für Molekulare Medizin (MDC); Max-Planck-Institut für Kolloid- und Grenzflächenforschung
Wissenschaftspark Potsdam-Golm; Zuse-Institut Berlin (ZIB)
Spokesperson Professor Dr. Rainer Haag