SFB 1449:  Dynamic Hydrogels at Biointerfaces

• Subject Area: Chemistry ; Biology ; Medicine
• Term: since 2021
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 431232613

The overarching goal of this CRC is to define the key physicochemical parameters that determine protective hydrogel function at biological interfaces in health, and abnormalities in disease for prospective development of novel therapeutic strategies. To achieve this goal, we will perform a detailed analysis of the physical, chemical and biological properties of synthetic and native hydrogels (i.e. mucus and glycocalyx). We focus on the individual and combined contributions of hydrogel components and their functional impact on airway and intestinal surfaces constituting the largest biointerfaces covered by hydrogels in the human body. In this context, we will include studies of exemplary pulmonary and gastrointestinal diseases, in which abnormal hydrogels 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 as 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 parameters define healthy vs. disease states. We base the approach on our unique capability to (bio)synthetically build key hydrogel components and compare them with the native hydrogels. The three main research objectives of the CRC are i) to determine the structure and role of individual hydrogel components, i.e. glycoproteins, salt and water, in the complex process of hydrogel formation and its function at biointerfaces; ii) to reconstitute synthetic mimics of native hydrogel components and study whether the synthetic hydro-gel variants can recapitulate the native barrier to prevent infection by bacteria and viruses; iii) to define the relationship of hydrogel properties (mucus/glycocalyx) in health vs. disease to design new therapeutic concepts.

• 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 and application of nanoviscosity probes in advanced FLIM studies on synthetic and native hydrogels in vitro (Project Heads Alexiev, Ulrike ;  Block, Stephan ;  Seitz, Oliver )
• A05 - Mapping the interdependency of the gut-lung-axis and hydrogel barrier in health and disease (Project Head Hedtrich, Sarah )
• B01 - The 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 virus 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 - The interplay of microbiota with mucus: (Project Heads Forslund-Startceva, Sofia ;  Fulde, Marcus )
• C01 - Semi-synthetic approaches to probe mucin function (Project Heads Hackenberger, Christian ;  Seitz, Oliver )
• C02 - Rationally designed mucin-like glyco and peptide hydrogels (Project Heads Delbianco, Martina ;  Keller, Bettina ;  Koksch, Beate )
• C03 - Proteomics and Glycomics of Glycocalix and Mucus (Project Heads Mertins, Philipp ;  Pagel, Kevin )
• C04 - Novel polymeric reducing agents as mucus modulators (Project Heads Haag, Rainer ;  Lauster, Daniel Christian ;  Mall, Marcus )
• 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 )
• Z01 - Bioanalytical Core Unit (Project Heads Dernedde, Jens ;  Haag, Rainer ;  Mertins, Philipp ;  Pagel, Kevin )
• Z02 - In vitro and in vivo Hydrogel Model Systems Core Unit (Project Heads 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
• Spokesperson: Professor Dr. Rainer Haag