Unconventional ER exit pathway in mammalian Cells

真核细胞的一个标志是亚细胞细胞器的多样化排列，这些细胞器划分了生命所必需的各种生化反应。这些细胞已经发展出优雅的细胞过程，根据细胞的需要形成和维持各种细胞器。其中一个这样的过程是蛋白质正确靶向其指定的细胞器，以允许细胞器的特殊功能。蛋白质靶向的缺陷可导致关键细胞过程的失败，从而导致细胞死亡和/或疾病。我的研究小组对了解蛋白质通过内质网（ER）进入各种细胞器的机制很感兴趣。过氧化物酶体就是这样一种细胞器。这个小细胞器容纳酶，酶参与各种生物反应，这些反应对生物体的生存至关重要。然而，对过氧化物酶体如何形成的基本认识仍然缺乏。我们最近已经证明过氧化物酶体从内质网接收一些膜蛋白。这种从内质网到过氧化物酶体的蛋白质输出与传统的蛋白质出口途径无关。因此，我们研究计划的总体目标是了解哺乳动物细胞中蛋白质从内质网转运到过氧化物酶体的基本机制。我们将使用最先进的成像技术结合遗传学和生化技术来解决这个问题。这些研究将具有广泛的背景重要性，因为过氧化物酶体的功能在多细胞生物（如植物）之间是保守的，过氧化物酶体在植物的生长中起着关键作用。最终，通过这项研究的发现不仅将进一步加深我们对内质网过氧化物酶体形成的理解，而且通过这些研究开发的创新技术也可用于研究细胞生物学的其他主题。此外，它将为发展中的年轻科学家提供尖端显微镜技术的培训，这些年轻科学家将为加拿大学术界，政府和工业界的成功事业做好准备

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.**