Molecular and cellular mechanisms of selective autophagy and their relevance to ageing

现代医学的进步大大提高了人类的预期寿命。其结果是与衰老有关的疾病发病率增加。最近的研究表明，细胞自噬系统的破坏与衰老相关疾病的发展有关。自噬描述了细胞自我吞噬的基本过程。当环境变得不利时，细胞利用自噬来产生物质和能量。它们也用这个过程来清除受损的细胞成分。最初，人们认为自噬是一个随机过程，但越来越多的证据表明，自噬是通过高度控制、选择性和特异性的方式完成的。我们将使用果蝇（Drosophila melanogaster）作为一种可基因修饰的模式生物来研究衰老过程中的自噬，以及它如何有助于选择性处理可能导致衰老的受损和潜在有毒细胞物质。这些机制在果蝇和人类之间非常相似，因此研究结果将与人类健康直接相关。我们的目标是在分子水平上了解自噬是如何起作用的，以及如何确定特定的蛋白质被降解。然后，我们将研究这个过程在衰老过程中是如何受到影响的，以及它是如何开始分解并导致与年龄相关的疾病发展的。该项目将为我们了解选择性自噬的基本机制做出重大贡献，并可能用于旨在开发对抗年龄相关疾病和延长寿命的新策略的应用研究。

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 autophagy system in cells is involved in the development of ageing-related diseases. Autophagy describes the essential process of cellular self-eating. Cells use autophagy to generate materials and energy when conditions become unfavourable. They also use this process to clear damaged cellular components. Initially it was thought that autophagy was a random process but there is growing evidence it is accomplished in a highly controlled, selective and specific manner. We will use the fruit fly, Drosophila melanogaster, as a genetically modifiable model organism to investigate autophagy during ageing and how it can contribute to the selective disposal of damaged and potentially toxic cellular material which may be the cause of ageing. These mechanisms are very similar between fruit flies and humans, so the results will have direct relevance to human health.We aim to understand at molecular level how autophagy works and how specific proteins are identified to be degraded. We will then study how this process is affected during ageing and how it begins to break down and lead to age-related diseases developing.This project will make a major contribution to our understanding of the fundamental mechanisms of selective autophagy and could potentially be used in applied research aimed towards developing new strategies to fight age-related diseases and to extend lifespan.