Grant: Discovery Grants Program - Individual

A biological process called autophagy has garnered enormous attention due to its association with aging, nutrient metabolism, stress, and human diseases. Autophagy literally means "self-eating" and describes a process in which cells 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. Autophagy is also involved in numerous developmental processes such as cell growth, tissue remodeling, removal of cell fragments, acquisition of cellular traits and longevity. The core autophagy-related (Atg) proteins required for the autophagy process have been identified in multiple different organisms, but the regulatory inputs and molecular mechanisms by which autophagy carries out its cellular and physiological functions remain ill defined. The long-term goal of my research program is to elucidate the cellular functions and physiological roles 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 investigate the influence of sex on the function of autophagy and autophagy-related proteins. Our recent preliminary data, along with emerging evidence in the literature, indicate that sex influences autophagy-related phenotypes. However, the possible influence of sex is largely overlooked in the majority of autophagy investigations, especially since many autophagy studies are conducted in two dimensional cell culture systems. In this study, we will use the fruit fly model system to determine how sex influences autophagy responses and the functions of the core autophagy-related proteins. We will elucidate molecular mechanisms that contribute to sex-specific autophagy-related phenotypes, and be the first to perform a large unbiased screen to identify potential new modifiers of sexually dimorphic autophagy-related phenotypes. Overall, these short term goals will contribute important new knowledge that is fundamental to our long term goal of understanding the physiological roles of the core autophagy-related (Atg) proteins in the context of a whole organism.