Unconventional ER exit pathway in mammalian Cells

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A hallmark of eukaryotic cells is the diverse array of subcellular organelles that compartmentalize the various biochemical reactions essential to life. These cells have developed elegant cellular processes to form and maintain the various organelles based on the needs of the cell. One such process is the correct targeting of proteins to their designated organelle to allow for the specialized functions of the organelle. A defect in protein targeting can lead to failure of critical cellular processes leading to cell death and/or disease. My research group is interested in understanding the mechanisms through which proteins exit the endoplasmic reticulum (ER) to various organelles. One such organelle is the peroxisome. This small organelle houses enzymes, which are involved in a wide variety of biological reactions that are critical for the survival of the organism. Yet, a basic understanding how peroxisomes are formed is still lacking. We have recently shown that peroxisomes receive some of their membrane proteins from the ER. This export of protein from ER to peroxisomes is independent of conventional protein exit pathways. Therefore, the overall goal of our research proposal is to understand the basic mechanism(s) by which proteins are transport from the ER to peroxisome in mammalian cells. We will address this using state-of-the-art imaging technology coupled with genetics and biochemical techniques. These studies will have broad contextual importance since peroxisome function is conserved between multi-cellular organisms, like plants, where peroxisomes play a critical role in their growth. Ultimately, the findings through this research will not only further our understanding of peroxisome formation from the ER but also the innovative techniques developed through these studies can also be utilized to examine other topics of cell biology. Moreover, it will provide training in cutting-edge microscopy techniques to developing young scientists who will be well prepared for successful careers in Canadian academia, government, and industry.**