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Dr. Chris Overall
Departments of Oral Biological & Medical Sciences
Biochemistry & Molecular Biology
UBC Centre of Blood Research

Degradomics: Systems Biology of the Protease Web

Degradomics is the application of genomic and proteomic techniques to elucidate protease and protease-substrate repertoires—or ‘degradomes’—on an organism-wide scale. We coined this term and pioneered new proteomic techniques to identify cleaved substrates and the downstream effects of proteolysis by ICAT and iTRAQ proteomics. Together with our new proteomic approaches for identifying the N and C termini of proteins and their modifications using N and C Terminal Amine Isotope Labelling of Substrates (TAILS) and PICS (Proteomic Identification of Cleavage Specificity) we are taking a systems biology approach to identify new protease substrates in complex proteomes and in cellular contexts. As part of the Human Proteome Project we are using these high throughput technologies to assign the N and C-termini to proteins on Chromosome 6 and 21. Using a variety of mouse models of disease including arthritis and breast cancer we are applying these approaches to understand the role of proteolysis in sculpting the proteome and modifying signalling pathways. This systems biology approach is revealing new roles for proteases in vivo, new diagnostic indicators of disease, and new drug targets to treat disease.

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