Our lab is located in the Michael Smith Laboratories at the University of British Columbia. We are part of the Department of Medical Genetics, and associated with the Department of Biochemistry and Molecular Biology and the Genome Science + Technology graduate programs.
The major focus of our laboratory is the molecular biology of eukaryotic chromosome transmission. Genetic and molecular approaches are used to study determinants that control the mitotic and meiotic segregation of chromosomes in the yeast Saccharomyces cerevisiae. Genetic perturbation causing a chromosome instability (CIN) phenotype in cancer cells is now widely recognized to be a major predisposing condition in cancer initiation and/or progression. S. cerevisiae has proven to be an excellent experimental organism for the study of mitotic cell division and the chromosome transmission cycle. One line of research is aimed at defining the DNA sequence elements essential to centromere function and at identifying genes that encode or regulate the function of kinetochore proteins that directly interact with centromeric DNA. A second line of research involves analysis of a large reference collection of mutants (ctf mutants) that are defective in chromosome segregation and that define genes required for kinetochore function, sister chromatid cohesion, chromosome structure, and control of cell cycle progression at mitosis. A third line of research focuses on the Anaphase Promoting Complex (APC), which acts as an E3 activity in the ubiquitination of key cell cycle regulatory proteins (eg., mitotic cyclins) that regulate transition from metaphase to anaphase and exit from mitosis.
Our research is designed to analyze the molecular basis of genome stability in yeast and to identify cognate components in mammalian species. The long-term goal is to understand the mechanisms of action of these functions and how their activities are coordinated in the cell cycle. Basic studies on genes required for chromosome transmission fidelity, kinetochore function, and mitotic checkpoint surveillance (basic themes of our research) are directly relevant to cancer. Further elucidation of the genetic basis of CIN in model organisms will provide a mechanistic basis for understanding this process, and will provide candidate genes for those CIN genes mutated in cancer. Knowledge gained from this work therefore provides insight into normal cell cycle controls and how these controls are overridden in disease.
The major focus of our laboratory is the molecular biology of eukaryotic chromosome transmission.