CAREER: Spatiotemporal Regulation of Clathrin-mediated Endocytosis

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This Faculty Early Career Development (CAREER) project is designed to understand the mechanisms employed by cells to regulate the uptake of membrane-bound molecules into cells. Cells often use a protein called clathrin to coat membranes which in turn engulf molecules that are bound for internalization. The results of this project will provide a comprehensive understanding of clathrin-mediated internalization that can be extended to the everyday interaction of cells with their environment. This research program will also help establish educational outreach activities for high school students from underrepresented areas of Columbus, OH. To attract young generations to science, research opportunities and a program of seminars will be organized in collaboration with a local tuition-free public high school. The PI will initiate a new program, Self Efficacy in STEM thRough Vicarious Experience (SERVE), to alleviate gender imbalance in STEM fields by boosting female student's self-efficacy in math and sciences. The PI will ensure that the graduate students in his research group will actively participate in the outreach activities and develop skills required for conveying their scientific knowledge and experience to non-scientific audiences. The PI will also work in partnership with the Ohio State University Master's to PhD Bridge Program to support and train a master's level student from underrepresented groups. Despite being the most intensely studied membrane transporters, due to the lack of experimental approaches that allow correlation of structural and temporal properties of clathrin coats, fundamental aspects of clathrin-mediated endocytic mechanism remain unclear. Research led by the PI revealed that the mechanical properties of cells dictate the dynamic and structural properties of endocytic clathrin coats. In the first part of this CAREER research program, the PI will characterize the initiation and maturation dynamics of endocytic clathrin-coated structures at distinct membrane tension and curvature levels to establish the factors determining the initiation, stability and curvature of endocytic clathrin coats. The PI will then determine the dynamics of clathrin-coated structures during cellular processes associated with spatiotemporal tension gradients to elucidate the origin of heterogeneity in clathrin-mediated endocytic trafficking in cells. Characterizing the spatiotemporal regulation of clathrin coat formation and identifying the molecular underpinnings of its heterogeneity will develop a holistic view and systems level understanding of clathrin-mediated endocytosis. The long term goals of this CAREER development plan will allow researchers to delineate the interplay between mechanical cues and membrane traffic during cellular and tissue level morphological changes that are essential for normal biological function.