Grant: Project Grant

Autophagy is a cellular process capable of degrading subcellular components in response to stress. One of the best characterized stressors that upregulates autophagy is nutrient starvation. Under starvation there is an increase in autophagy, a cellular recycling program, which helps survival and maintains essential cellular functions. Dysregulation of autophagy has been described in several human diseases. In this grant we are focused on characterizing how signaling from nutrient sensors is transmitted to the autophagy pathway. We have discovered multiple mechanisms linking a key enzyme in the autophagy pathway to nutrient sensing. By uncovering these regulatory pathways, we will gain a better understanding of the cellular stress response and the mechanisms contributing to autophagy related disease. To realize the biological impact of these fundamental discoveries the principal applicant has assembled a group of researchers who are experts in mouse models of disease, fly genetic models, and a mass spectrometry lab, which will compliment our expertise in pathway identification. We also have a standing collaboration with a major biotechnology company Abcam, who will build tools to assist the study and make them available to the research community.