UbiBodies - A New Generation of Specific and Versatile Single Domain Antibodies Against Ubiquitin Chains

• Applicant: Julian Koch
• Subject Area: Biochemistry ; Cell Biology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 521996691

Ubiquitination, the modification of target proteins with the 8.6 kDa protein Ubiquitin, is now recognised as one of the largest and most complex signalling systems in eukaryotic cells. It controls virtually all aspects of cell biology through eight distinct types of polymeric Ub modifications (Ub chains) assembled on substrates. Yet, we know very little about the cellular functions of the six so-called ‘atypical’ chains. This is mainly due to a lack of reagents that can specifically detect these chains. I aim to pioneer the development of a new class of Ub chain-specific single domain antibody (sdAbs) reagents and use them to start elucidating hitherto unknown fundamental biology regulated by atypical Ub. Large, highly diverse phage libraries of sdAbs will give us a competitive edge for in vitro selection by phage display. Starting with one highly relevant Ub chain type, M1-Ub, this project will set up a workflow for generating and testing Ub chain-specific sdAbs. The Ub chain-specific sdAbs, termed ‘UbiBodies’, will be used for detection, enrichment, and functional, cellular analyses of individual Ub chain types. Our UbiBodies will therefore establish a new regimen of reagents that allow studies of the largely unexplored roles of the atypical Ub chains with immense potential for ground-breaking discoveries in the field of cell biology.

• DFG Programme: WBP Fellowship
• International Connection: Denmark
• Host: Professor Rune Busk Damgaard, Ph.D.