Grant

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

Funder: European Commission

Dimensions: grant.8587222

Affiliations

Organisations

  1. (1) Institute of Molecular Biology, grid.424631.6
  2. (2) University of Tartu, grid.10939.32
  3. (3) GlaxoSmithKline (United Kingdom), grid.418236.a
  4. (4) Hebrew University of Jerusalem, grid.9619.7
  5. (5) ETH Zurich, grid.5801.c
  6. (6) Uppsala University, grid.8993.b
  7. (7) University of Copenhagen, grid.5254.6, KU

Research Organisations

Abstract

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.

NORA University Profiles

University of Copenhagen

Funding information

Funding period: 2019-2023

Funding amount: EUR 4147223

Grant number: 860517

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Fields of Research