Cataloguing Chromosome Instability Mutants: Implications for Cell Biology, Cancer and Therapeutics

The accumulation of mutations in the DNA of human cells can lead to tumour formation. More than 80 percent of solid tumours exhibit chromosome instability (CIN) – the property that results in an unequal distribution of DNA to each daughter cell upon cell division. The genetic instability associated with these tumours may allow them to adapt quickly and remain in the body.

Dr. Peter Stirling's research is focused on generating a comprehensive database of genetic mutations that lead to CIN, using the Baker's yeast cell model. The results will then be translated to related human genes. Using yeast to identify candidate human CIN genes has already been successful for a handful of genes and Dr. Stirling's project will extend this effort. The candidate CIN genes identified will provide important insight into the biology underlying tumour formation. Further, the results will validate interesting CIN genes relevant to cancer in human cells and provide greater understanding regarding the mechanisms of CIN for those genes.

Additionally, Dr. Stirling is also working to identify secondary genes whose mutations cause cell death in combination with a CIN mutation. By validating these "synthetic lethal mutant gene combinations" in human cells, Dr. Stirling will have defined drug targets for tumours carrying mutations in a particular CIN gene. And, working in collaboration with researchers at the University of British Columbia, Dr. Stirling will identify small molecules (i.e. drugs,) that selectively kill tumour cells based on the identified second-site mutations. Overall, the results will reveal new aspects of tumour biology, identify new anti-cancer drug targets and contribute to the development of new anti-cancer drugs.