Spatial and temporal mechanisms underlying aggregate formation

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This project will address fundamental questions about how cells respond to and manage newly misfolded and aggregating proteins. Proteins are folded into specific shapes that confer function; however, through aging or stress, proteins can undergo misfolding and can aggregate. This change in shape due to misfolding and aggregation can alter the function of the protein. The goal of this project is to understand how the cell initially responds and manages these newly formed aggregates. This project will have broader impacts by providing training opportunities for non-traditional groups in STEM, specifically by integrating underrepresented minorities and first-generation students in transformational research experiences. Additionally, the PI will continue to provide accessible research experiences to students at a rural institution, many of whom are first generation, through an inquiry-based laboratory course focused on protein aggregation. This project will identify the cellular mechanisms that move and sequester newly formed protein aggregates in both space and time using a powerful suite of tools that pair microscopy, genetics, and biochemistry. Experiments will determine how cytoskeletal networks contribute to the trafficking of different types of aggregates within the cell, and how aggregates are sequestered over time. Taken together, this project will provide a mechanistic understanding at the molecular level of how the cell manages newly formed aggregates and reveal conserved pathways that ensure a proper response in the presence of stress or age.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.