Regulation of isolation membrane remodelling during autophagosome biogenesis by sorting nexins

自噬描述了细胞自我吞噬的有趣而重要的过程。它存在于从酵母到人类的生物体中，进一步证明了它对动物，植物和真菌王国细胞的重要性。细胞利用自噬产生能量和物质，以便在条件变得不利时生存。它们还利用这一过程来处理受损和潜在有毒的细胞成分。这对于长寿细胞尤其重要，例如我们大脑中的神经元，它们必须多年来科普作为细胞功能正常结果而发生的累积损伤。我们现在知道了很多关于自噬是如何在细胞中触发的，以及负责形成自噬体的分子-自噬体是自噬途径的功能单元的膜结合载体-但我们仍然不了解这些结构是如何在细胞内组装的。存在一个称为分选连接蛋白（SNX）的蛋白质大家族，它们在重塑我们细胞内的现有膜中发挥重要作用。我们有初步证据表明其中一些在自噬中的作用，现在希望详细了解这些蛋白质的作用。我们将使用最先进的显微镜和生化分析来描述SNX如何调节正在经历饥饿或试图去除有毒内含物的细胞中的自噬。这些研究将大大推进我们对自噬过程中膜动力学的理解。

Autophagy describes the intriguing and essential process of cellular self-eating. It is found in organisms ranging from yeast to man, further demonstrating its importance for cells across the animal, plant and fungal Kingdoms. Cells use autophagy to generate energy and materials in order to survive when conditions become unfavourable. They also use this process to dispose of damaged and potentially toxic cellular components. This is particularly important in long-lived cells such as the neurons in our brains which have to cope over many years with the cumulative damage that occurs as a normal consequence of cellular function. We now know much about how autophagy is triggered in cells and the molecules responsible for the formation of autophagosomes - the membrane-bound vehicles that are the functional units of the autophagy pathway - but we still do not understand how these structures are assembled within cells. There exists a large family of proteins called sorting nexins (SNXs) that play important roles in remodelling existing membranes within our cells. We have preliminary evidence for a role for some of these in autophagy, and now wish to understand in detail how these proteins act. We will use state-of-the-art microscopy and biochemical assays to describe how SNXs regulate autophagy in cells that are undergoing starvation or are attempting to remove toxic inclusions. These studies will significantly advance our understanding of membrane dynamics during autophagy.