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性，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，以根据细胞的需要形成和维持各种细胞器。一个这样的过程是将蛋白质正确地定位到它们指定的细胞器，以实现细胞器的特殊功能。蛋白质靶向的缺陷可能导致关键的细胞过程失败，导致细胞死亡和/或疾病。我的研究小组感兴趣的是了解蛋白质通过内质网(ER)进入各种细胞器的机制。其中一个细胞器就是过氧化物体。这种小的细胞器含有酶，这些酶参与了对有机体的生存至关重要的各种生物反应。然而，对过氧化物体是如何形成的仍然缺乏基本的了解。我们最近已经证明，过氧化体从内质网接收到它们的一些膜蛋白。这种从内质网到过氧化体的蛋白质输出不依赖于传统的蛋白质退出途径。因此，我们的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运输到过氧化酶体的基本机制(S)。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，因为过氧化物体功能在多细胞生物体之间是保守的，如植物，在这些生物体中，过氧化物体在它们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中过氧化物体形成的理解，而且通过这些研究开发的创新技术也可以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方面的培训，他们将为在加拿大学术界、政府和工业界成功的职业生涯做好充分准备。**

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.**