Grant: Doctoral: Vanier Canada Graduate Scholarships

We have only limited knowledge of the mechanisms underlying the formation of a peroxisome, an organelle responsible for many biochemical reactions, notably lipid metabolism. Peroxisomes are essential for normal human development and physiology, as demonstrated by the lethality of the peroxisome biogenesis disorders, a group of autosomal recessive diseases in which multiple peroxisomal metabolic pathways are dysfunctional because peroxisome biogenesis is compromised. Peroxisome biogenesis is controlled by at least 32 proteins termed peroxins that are encoded by the PEX genes. To date, mutations in 12 PEX genes have been shown to give rise to the peroxisome biogenesis disorders. De novo peroxisome biogenesis occurs at the endoplasmic reticulum, another compartment in the cell, and the trafficking of proteins from the endoplasmic reticulum to the peroxisome and the control of peroxisome division prior to inheritance of peroxisomes during cellular division is poorly characterized. My novel work showing that some members of the Pex28p/29p and Pex30p/31p/32p family of proteins localize to both the endoplasmic reticulum and the peroxisome and our previous work showing that these proteins are involved in controlling peroxisome size and number will allow us for the first time to address all these aspects of peroxisome biogenesis that hitherto had remained enigmatic. I am currently working on defining the precise role these proteins play in regulating peroxisome formation, division and inheritance. This work will significantly advance our understanding of basic peroxisome biology and of the relevance of peroxisomes in human development. Given that an understanding of the molecular mechanisms controlling peroxisome biogenesis is key to understanding the peroxisome biogenesis disorders, elucidating the role Pex28p/29p and Pex30p/31p/32p play in this process will open up increased possibilities for curing these diseases.