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A chemo-affinity toolkit for methylation proteomics

  • Project Leaders: Fraser Hof
  • Institutions: University of Victoria (UVic)
  • Budget: $238,800
  • Competition: 2015 Disruptive Innovation in Genomics - Phase 1
  • Fiscal Year: 2016
  • Status: Active

Human cells contain tens of thousands of proteins, most of them controlled by modifications that can be as small as a single carbon atom with three hydrogen atoms (“methyl group”) added in subtly different ways. Although they are small, these modifications have critical roles to play in switching proteins on or off, or dramatically changing their interaction networks. The analysis of modifications like methyl groups is challenging, because of their chemically subtlety and low abundance. As well, antibodies, though flexible and powerful, are inherently challenged when it comes to the global analysis of methyl modification. Researchers and clinical testing centres worldwide lack a global, reliable, and universally accepted method for doing methyl analysis. The market for methyl-targeted research and diagnostics is growing rapidly and ripe for disruption.

Dr. Fraser Hof and his team at the University of Victoria specialize in supramolecular chemistry – the science of making chemicals that selectively bind other molecules. The team will adapt a family of binding chemicals that can bind methylated proteins. With this proof-of-concept work, the team will demonstrate that agents with the required selectivity are achievable, and establish that they can operate within normal protein analysis (proteomics) workflows. Chemical agents of these kinds can be made in highly reproducible, pure batches, meaning that their performance from batch to batch and lab to lab may be intrinsically superior to those of antibodies. This foundational technology has the potential to transform methylation research, lead to new medicines and diagnostics, and drive new science in dozens of research labs and thousands of diagnostics centres.