Title of the presentation:

A systems biology approach to studying organelle biogenesis: a voyage from gene transcription to organelle inheritance.

Biography:

Dr. Richard Rachubinski is Distinguished University Professor and Chair of the Department of Cell Biology at the University of Alberta. After receiving a Ph.D. in cell biology in the laboratory of Dr. John Bergeron at McGill University in 1980, he pursued postdoctoral research at McGill with Dr. Gordon Shore and then at The Rockefeller University in New York with Dr. Paul Lazarow, where he began his continuing interest in peroxisome biogenesis and function. He was Assistant, Associate, and Full Professor in the Department of Biochemistry at McMaster University before assuming his current position at the University of Alberta in 1993. In 2001, he was named Canada Research Chair in Cell Biology and Senior Investigator of the Canadian Institutes of Health Research. In 2002, he was appointed a fellow of the Royal Society of Canada. He has been an International Research Scholar of the Howard Hughes Medical Institute since 1997. His work centers on defining the molecular pathways controlling the biogenesis of the peroxisome, a cellular organelle that performs a variety of important biochemical functions, notably in lipid metabolism and reactive oxygen species detoxification.

Abstract:

A systems biology approach to understanding organelle biogenesis: a voyage from gene transcription to organelle inheritance

Richard A. Rachubinski, Department of Cell Biology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada

John D. Aitchison, Institute for Systems Biology, Seattle, Washington 98103, USA

The peroxisome is an ubiquitous organelle that compartmentalizes a variety of important biochemical functions, notably the oxidation of fats and the inactivation of reactive oxygen species. The requirement for functional peroxisomes is underscored by the lethality of a group of inherited peroxisomal disorders, collectively called the peroxisome biogenesis disorders, in which peroxisomes fail to assemble. One of the exceptional properties of peroxisomes is their highly dynamic nature with respect to changing environmental conditions. We have undertaken a systems biology approach using baker's yeast, Saccharomyces cerevisiae, to achieve a global and predictive understanding of peroxisome assembly, function and dynamics. In our practice of systems biology, we aim to enumerate and quantify all relevant molecular constituents and their interactions involved in the global response governing peroxisome formation; computationally integrate different data types; mathematically model our biological system; and test predictions arising from our systems biology analysis of peroxisomes. Our systems biology approach has centered on 1) transcriptional networks, with a focus on parallel combinatorial control to control timing of the transcriptional response with respect to changes in the environment; 2) quantitative proteomics to evaluate the enrichment of proteins in peroxisomes and define bona fide time- and condition-specific constituents of peroxisomes (proteins move); and 3) a comprehensive screen of the yeast gene deletion library expressing a fluorescently labeled peroxisomal protein to reveal the complexity of the peroxisome biogenic response through quantitative imaging and to identify novel aspects of, and players in, peroxisome biology. Our ultimate goal is a reliable and predictive model of the peroxisome with regard to its biogenesis, function and response in an ever changing environment. This work was supported by grants from the Canadian Institutes of Health Research and the Howard Hughes Medical Institute to R.A.R. and the National Institutes of Health to J.D.A.