Lipid transport machinery in cellular membranes

细胞是地球上所有生命形式的最小单位，它使用脂肪和水作为主要介质，允许生物因素充分发挥细胞生存的功能。脂肪是单个细胞内和细胞表面的细胞屏障的积木。这些屏障创建了防水隔间，以允许多种生物和化学反应同时进行，并提供了允许反应产物在内部细胞隔间或相邻细胞之间传播的通道。脂类是脂肪的微观元素，为了生存，细胞要保持脂池的平衡，并将各种脂类放置在适当的范围内。关键的生物学问题是，是什么控制着脂类跨越脂肪屏障的及时交换，以及对生物体内脂类总水平的准确反应。我们的研究将调查脂肪是如何通过蛋白质机制跨越这些脂肪屏障的，这是了解细胞如何生存的关键因素。具体地说，这项NSERC项目将专注于一组被称为“活性脂类转运蛋白”的脂类运输蛋白。这种类型的蛋白质驻留在脂肪屏障中，并消耗ATP(所有生物中的主要能量货币)，将脂质从屏障的一侧输送到另一侧。我们的研究团队将通过分析潜在的脂肪控制功能的微观事件，并通过建立模型来了解原子细节，来研究这种类型的蛋白质是如何工作的。最终，我们的研究计划将为全面了解化学和物理基础奠定基础，这些基础将解释“活性脂质转运体”失活对所有活着的有机体细胞生存的影响。

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.