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Short linear interaction motifs as specificity determinants in the ubiquitin system – discovery, mechanisms and therapeutic opportunities

Project description

Better understanding of the ubiquitin system

The ubiquitin system is a promising source of therapies for the treatment of numerous human diseases that pose a societal challenge. Short linear interaction motifs, or SLiMs, are important in the mechanisms that allow the ubiquitin system to be used for treating some diseases, but they remain underused. The EU-funded UBIMOTIF project aims to train young researchers in the science of SLiMs using a multidisciplinary and intersectoral approach along with cutting edge technology. The impact of UBIMOTIF will be unprecedented, providing insight into the ubiquitin system as well as novel therapeutic opportunities and a skilled workforce that can fill the exhausted pipelines of European companies.

Objective

A major challenge is the lack of therapeutic approaches for numerous human diseases, which poses a societal challenge. The ubiquitin system is a major promising source for novel therapeutic approaches but its potential has not been fully exploited due to limited insight and lack of researchers trained in understanding and identifying avenues to target the ubiquitin system. Ubiquitin ligases and deubiquitinating enzymes (DUBs) comprises enzymes that actively add or remove ubiquitin from proteins to regulate cell physiology. How these enzymes selectively recognize their substrates is largely unknown but an emerging theme is that a globular domain in the enzyme binds a short linear interaction motif (SLiM) in the substrate. SLiMs are short peptide motifs that constitute ideal entry points for understanding the ubiquitin system as they provide detailed insight into substrate selection and how this regulates the underlying biology. Further, SLiMs provide direct routes to therapeutic exploitation as they serve as peptide scaffolds for drug development and tools to highjack the ubiquitin system. The potential of SLiMs has not been capitalized upon because a method for efficient identification was missing, interactions between relevant partners were lacking and this has hampered training of young researchers. UBIMOTIF overcomes these barriers by exploiting novel technological advances to identify SLiMs and uniting outstanding complementary researchers and industrial partners with a common vision to provide outstanding training of early career scientist in SLiMs and the ubiquitin system. The UBIMOTIF topic provides ideal training of young researchers, as it requires a multidisciplinary and intersectorial approach providing training in multiple cutting-edge technologies. The impact of UBIMOTIF will be unprecedented insight into the ubiquitin system, novel therapeutic opportunities and a skilled workforce that can fill the exhausted pipelines of European companies.

Coordinator

KOBENHAVNS UNIVERSITET
Net EU contribution
€ 808 268,10
Address
NORREGADE 10
1165 Kobenhavn
Denmark

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Region
Danmark Hovedstaden Byen København
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 808 268,10

Participants (10)