Thursday, November 21, 2024
11/21/2024
Project Summary Emerging findings by us and others have revealed critical non-lethal functions of caspases across diverse animal phyla. Our published and unpublished findings indicate marked roles for caspases in ensuring multiple aspects of development including cell-cell communication, cell migration, protein homeostasis, and regulating stress responses. Moreover, our data indicate that a caspase target expressed in the same cell at the same time as the caspase may not be acted upon by the caspase until a specific developmental time point suggesting additional layers of regulation. It is not known how specific non-lethal caspase functions are mediated. Based on our recent findings, it is likely that caspases require other components, such as E3 ligases, to execute these non-lethal functions. We hypothesize that caspases function in complexes with other proteins that confer non-apoptotic specificity according to developmental stage, tissue type, and environmental status. Over the next five years, the critical goals for my lab are to: 1) identify how caspase modulates p38 MAPK-mediated signaling network to support neuronal integrity, 2) understand how UBR E3 ligases coordinately regulate cell fate, and 3) identify novel caspase functions in gene expression and metabolic regulation. Our proposed cross-disciplinary studies include genetic screens, biochemical analyses, translatomics, proteomics, metabolomics, and structure-function studies. The objective of the proposed studies is to understand how proteolytic mechanisms mediate diverse cellular regulatory functions in response to developmental or environmental cues.
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