Molecular mechanisms of selective autophagy during the course of ageing

现代医学的进步使人类的预期寿命大大延长。其后果之一是与衰老有关的疾病的发病率增加。最近的研究表明，细胞中自噬的蛋白水解细胞机制的破坏参与了衰老相关疾病的发展。自噬是一个重要的分解代谢过程，涉及通过溶酶体途径降解细胞质物质。当条件变得不利时，细胞利用自噬产生物质和能量。它们也利用这个过程来清除受损的细胞成分。我们将使用果蝇作为一个遗传修饰的模式生物内体运输和选择性自噬在体内衰老过程中的相互作用的机制进行调查。这些机制在果蝇和人类之间非常相似，因此结果将与人类健康直接相关。该项目的主要目标是：1）检查自噬相关蛋白和调节内体运输的蛋白质之间的相互作用2）检查磷酸化是否介导并定义上述相互作用3）检查内体运输突变体如何通过自噬调节衰老。

Advances in modern medicine have led to a significant increase in human life expectancy. A consequence of this has been the increase of the frequency of ageing-related diseases. Recent studies have indicated that a breakdown of the proteolytic cellular machinery of autophagy in cells, is involved in the development of ageing-related diseases. Autophagy is an essential catabolic process that involves the degradation of cytoplasmic material through the lysosomal pathway. Cells use autophagy to generate materials and energy when conditions become unfavourable. They also use this process to clear damaged cellular components. We will use the fruit fly Drosophila melanogaster as a genetically modifiable model organism to investigate the mechanisms of interplay between endosomal trafficking and selective autophagy during ageing in vivo. These mechanisms are very similar between fruit flies and humans, so the results will have direct relevance to human health. The main objectives of the project are: 1) To examine the interaction between autophagy-related proteins and proteins that regulate endosomal trafficking 2) To examine whether phosphorylation mediates and defines the above interactions 3) To examine how endosomal trafficking mutants regulate ageing through autophagy.