Lipid transport machinery in cellular membranes

细胞膜中的脂质运输机制

• 批准号: RGPIN-2018-04070
• 负责人: Lee, JyhYeuan
• 金额: $ 2.26万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=744324
• 关键词: Lipid; transport; machinery; cellular; membranes

Cells, the minimal unit of all life forms on Earth, use fat and water as the primary media to allow biological factors to operate in full function for cell survival. Fat is the building block of cellular barriers inside individual cells and on the cell surface. These barriers create waterproof compartments to allow multiple biological and chemical reactions to work simultaneously, and also provide gateways allowing reaction products to travel among the internal cell compartments or between adjacent cells. Lipids are the microscopic elements of fat, and to survive, cells keep the lipid pool in balance and place various kinds of lipids in their appropriate confines. The critical biological question is what controls the timely exchange of lipids across the fat barriers and the precise response to the total level of lipids in a living organism. Our research will investigate how lipids are moved across such fat barriers by protein machineries, a key element to understanding how cells survive. Specifically, this NSERC project will focus on a group of lipid trafficking proteins called “active lipid transporters”. This type of proteins resides in the fat barriers and consumes ATP (the primary energy currency in all living beings) to pump lipids from one side of the barriers to the other side. Our research team will study how this type of proteins works by analyzing the microscopic events underlying their fat-controlling function and by building models to see through the atomic details. Ultimately, our research program will lay the foundation for comprehensive understanding the chemical and physical basis that will explain the impact of inactivation of “active lipid transporters” on the cell survival in all living organisms.

细胞是地球上所有生命形式的最小单位，它以脂肪和水为主要媒介，使生物因子在细胞生存中充分发挥作用。脂肪是细胞内部和细胞表面的细胞屏障的组成部分。这些屏障形成了防水隔室，允许多种生物和化学反应同时进行，也提供了通道，允许反应产物在内部细胞隔室之间或相邻细胞之间流动。脂质是脂肪的微观成分，为了生存，细胞保持脂质池的平衡，并将各种脂质置于适当的范围内。关键的生物学问题是，是什么控制着脂质跨越脂肪屏障的及时交换，以及生物体内脂质总水平的精确反应。我们的研究将调查脂质是如何通过蛋白质机制越过这些脂肪屏障的，这是理解细胞如何生存的关键因素。具体来说，这个NSERC项目将关注一组被称为“活性脂质转运蛋白”的脂质转运蛋白。这种类型的蛋白质存在于脂肪屏障中，并消耗ATP（所有生物的主要能量货币）将脂质从屏障的一边泵到另一边。我们的研究团队将通过分析这类蛋白质控制脂肪功能背后的微观事件，并通过建立模型来观察原子细节，来研究这类蛋白质的工作原理。最终，我们的研究计划将为全面理解化学和物理基础奠定基础，这将解释“活性脂质转运体”失活对所有生物细胞存活的影响。