Macroautophagy in Drosophila development

最近，一种被称为自噬的生物过程引起了人们的极大关注，因为它与衰老、营养代谢、压力和人类疾病有关。自噬的字面意思是“自我吞噬”，描述的是细胞，即我们身体组织的组成部分，降解自己的一部分，以便回收和再利用的过程。这一过程通常用于维持动态平衡，但也可以作为一种适应性反应，使细胞能够在营养缺乏等应激条件下生存下来。越来越多的证据表明，自噬还参与了许多发育过程，如细胞生长、组织重塑、细胞碎片的去除、细胞特征的获得和长寿。然而，自噬影响这些发育过程的机制仍然不清楚。我的研究计划的长期目标是阐明自噬在整个有机体的正常发育中的功能。为了实现这一目标，我和我的受训者将利用一个简单的生物模型系统--果蝇，它与人类分享许多遗传和细胞成分，包括自噬所需的成分。这项提议的短期目标是研究自噬和脂类代谢之间的联系。了解这些联系很重要，因为脂类代谢的调节可能是自噬影响动物发育和应激反应的重要方式之一，而且我们知道脂类本身对生长、能量储存和细胞信号传递等过程至关重要。在这项研究中，我们将确定自噬和脂代谢的新调节因子，并阐明当这些调节因子改变时对生物体的影响。 总体而言，这项研究将为自噬功能和脂肪代谢之间的联系提供宝贵的见解，并有助于理解在发育过程中调节这些过程的生理效应。这项研究的另一个结果将是确定通过自噬调节脂质周转所需的新成分--因为这是一个新的研究领域，拟议的研究将提供独特的培训机会，它具有高度创新和重大影响的潜力。

A biological process called autophagy has garnered enormous attention recently due to its association with aging, nutrient metabolism, stress and human diseases. Autophagy literally means "self-eating" and describes a process in which cells, components of tissues in our bodies, degrade parts of themselves for recycling and re-use. This process typically serves to maintain homeostasis but it can also act as an adaptive response, enabling cells to survive conditions of stress such as nutrient deprivation. Accumulating evidence indicates that autophagy is also involved in numerous developmental processes such as cell growth, tissue remodeling, removal of cell fragments, acquisition of cellular traits and longevity. However, the mechanisms by which autophagy impacts these developmental processes remain ill defined. The long-term goal of my research program is to elucidate the functions of autophagy in normal development in the context of a whole organism. To achieve this goal, my trainees and I will utilize a simple model organism system, the fruit fly, which shares many genetic and cellular components with humans including those required for autophagy. The short-term goal of this proposal is to examine the links between autophagy and lipid metabolism. It is important to understand these links because the regulation of lipid metabolism may be one essential way that autophagy impacts animal development and stress responses, and because we know that lipids themselves are crucial for processes such as growth, energy storage and cell signaling. In this study, we will identify new regulators of autophagy and lipid metabolism, and elucidate the consequences to an organism when these regulators are altered.      Overall, this research will provide invaluable insights into the links between autophagy function and lipid metabolism, and contribute to an understanding of the physiological effects of modulating these processes in different tissues during development. Another outcome of this research will be the identification of new components that are required for regulating lipid turnover by autophagy – because this is a newly emerging research area, the proposed research will provide unique training opportunities and it has potential for high innovation and significant impact.