Decoding the Ubiquitin and Autophagy Signaling Networks - ABSTRACT The research program described in this proposal focuses on an in-depth exploration of the ubiquitin and autophagy pathways, which partake in a process called proteome homeostasis, or proteostasis, and is an essential cellular process. Over the course of this proposal, our team aims to uncover novel aspects of molecular intricacies of ubiquitin regulation and to explore the mechanisms underlying selective autophagy in response to various cellular stimuli. Regarding the ubiquitin machinery aspect of our work, our goal is to identify and understand the cellular relevance of recently discovered regulatory switches for ubiquitin signaling. For the autophagy facet of our work, we aim to enhance our comprehension of singular regulatory factors we’ve identified, which are involved in this complex biological process. This program combines our expertise in quantitative mass spectrometry, biochemistry, and cell biology to investigate the different aspects of proteostasis dynamics and its disruption in proteostasis-related diseases. Our investigation aims not only to advance scientific knowledge but also to have a substantial impact on healthcare by reducing our current limitations in understanding disease mechanisms.