Project Details
SFB 1449: Dynamic Hydrogels at Biointerfaces
Subject Area
Chemistry
Biology
Medicine
Biology
Medicine
Term
since 2021
Website
Homepage
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 431232613
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
- A01 - Hydrogel properties on airway surfaces in health and muco-obstructive lung disease (Project Heads Gradzielski, Michael ; Mall, Marcus )
- A02 - Rheology and mesoscopic structure-dynamics relations of hydrogels (Project Heads Gradzielski, Michael ; Netz, Roland )
- A03 - Probing and modeling of transport properties of hydrogels (Project Heads Block, Stephan ; Netz, Roland )
- A04 - Development, characterization and application of nanoprobes for advanced FLIM studies of synthetic and cellular hydrogels (Project Heads Block, Stephan ; Seitz, Oliver )
- A05 - Mapping the interdependency of the gut-lung-axis and hydrogel barrier in health and disease (Project Heads Bartfeld, Sina ; Hedtrich, Sarah )
- B01 - The alveolar epithelial glycocalyx at the blood-gas barrier of the lung (Project Heads Kübler, Wolfgang ; Ochs, Matthias )
- B02 - Functional role of the alveolar epithelial glycocalyx in pulmonary defense and inflammation (Project Heads Seeberger, Peter H. ; Witzenrath, Martin )
- B03 - Synthesis, biophysical characterization and penetration of mucus-inspired dynamic hydrogels (Project Heads Block, Stephan ; Haag, Rainer )
- B04 - Hydrogel Properties on Intestinal Surfaces in Health and Disease (Project Heads Siegmund, Britta ; Weinhart, Marie )
- B05 - Mucus-microbiota interplay along the gut-lung-axis (Project Heads Forslund-Startceva, Sofia ; Fulde, Marcus ; Schaupp, Laura )
- C01 - Semi-synthetic approaches to probe mucin function (Project Heads Hackenberger, Christian ; Pagel, Kevin ; Seitz, Oliver )
- C02 - Rationally designed mucin-like glyco and peptide hydrogels (Project Heads Delbianco, Martina ; Keller, Bettina ; Koksch, Beate )
- C03 - Glycomic remodeling of glycocalyx and mucus (Project Heads Mertins, Philipp ; Nouailles, Geraldine ; Pagel, Kevin )
- C04 - Novel polymeric reducing agents as mucus modulators (Project Heads Haag, Rainer ; Lauster, Daniel Christian ; Mall, Marcus )
- C05 - Characterization and modulation of protein-retention in hydrogels (Project Heads Hackenberger, Christian ; Lauster, Daniel Christian )
- INF - Information Management and Information Infrastructure in the Collaborative Research Center (Project Heads Ludwig, Kai ; Schütte, Christof )
- MGK - Integrated Research Training Group IRTG “Dynamic Hydrogels at Biointerfaces” (Project Heads Block, Stephan ; Haag, Rainer ; Koksch, Beate ; Pigaleva, Marina )
- Z01 - Bioanalytical Core Unit (Project Heads Dernedde, Jens ; Haag, Rainer ; Ludwig, Kai ; Mertins, Philipp ; Pagel, Kevin ; Pigaleva, Marina )
- Z02 - In vitro and in vivo Hydrogel Model Systems Core Unit (Project Heads Duerr, Julia ; Mall, Marcus ; Siegmund, Britta ; Weinhart, Marie )
- Z03 - Central Tasks of the Collaborative Research Center (Project Head Haag, Rainer )
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)
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