Project Details
Projekt
Coordination Funds
Applicant
Professorin Dr. Sabine Strahl
Subject Area
Biochemistry
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 289991887
The overwhelming success of massive genome sequencing can give the impression that the key to understanding life lies only in our genome. Strikingly, however, there are other layers of complexity; one of the most diverse is the post-translational modification of proteins by combinations of different sugar moieties, which is found in all domains of life. N-glycosylation, O-mannosylation and C-mannosylation are prevalent and highly conserved glycosylation pathways. Their precise interplay is essential for proper protein function, with effects ranging from enabling correct folding and protein localization to establishing precisely shaped gradients of secreted glycosylated morphogens. The glycosylation pathways start in the endoplasmic reticulum and in many cases the acceptor proteins receive more than one type of glycan. The crucial importance of the process is reflected by the wide range of hereditary diseases resulting from disruptions to these pathways (congenital disorders of glycosylation, CDGs) causing devastating, complex multisystemic syndromes.The extraordinary complexity of glyco-modification has severely hampered systematic approaches aiming at decoding their action across scales. To address this challenge, the Research Unit has gathered experts addressing glycosylation at and across all levels - from the structural to the inter-molecular, cellular, organ and the organismal. They combine genetic, structural and lipid biochemistry, glycomics and (glyco)proteomics, molecular and cell biology, as well as developmental approaches, always with a close focus on the patients’ perspective.The tight interactions of the participating groups in the first funding period have established new mechanistic insights and novel approaches that shed light on the molecular mechanisms underlying complex glycosylation disorders. Newly established animal models for CDGs provide the basis for the integration of the combined expertise to address the mechanistic implications, starting at the level of altered glycosylation and the resulting consequences for the decoration of the target proteins. Striking evidence underpins a tight interconnection of all three types of glycosylation, highlighting the need to study the complex effects as a team of synergizing experts in order to ultimately resolve structure function relationships and their consequences in the organismal context as a foundation for the development of novel diagnostic tools and new therapeutic approaches.
DFG Programme
Research Units
