Arp2/3 complex branching kinetics and cell motility

Yale University, New Haven CT

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Abstract

[unreadable] DESCRIPTION (provided by applicant): My background is in physics. I have experience in modeling, mechanical properties of soft condensed matter, and solid-state devices from Chih-Kang Shih's lab in Austin, Texas. My thesis project on the mechanical properties of cell and polymer gels has led me to my current career goal of becoming an independent biophysics researcher. Because my undergraduate and graduate training lacked a background in biology, I chose a biochemistry laboratory for my post-doctoral training. The Pollard lab has the microscopy, and biochemistry resources and expertise to complete my training. Additionally, structured group meetings and weekly journal article review sessions will broaden my understanding of all aspects of biochemistry, cell biology, and molecular biology. With the proposed research I plan to complete my post-doctoral training and proceed to a career in quantitative biophysics and bioengineering research with a strong background in the biologist's prospective. [unreadable] [unreadable] The actin cytoskeleton provides the majority of the structural stability to the cell shape and the dynamics of this network leads to cell motility. Cancer cells rely on this system for the motility in order to metastasize. Central to the rearrangement of the actin cytoskeleton is the nucleation of new actin filaments in specific regions of the cell cortex. The Arp2/3 complex provides efficient nucleation of new actin filaments from the sides of existing ("mother") filaments and may also contribute to nucleation in the absence of a mother filament. The branches provide structural stability and increase the propulsive force of the actin network. The purpose of my proposed research is to understand the branching mechanism and to find ways to inhibit branching. Existing methods for measuring the kinetics of branching have led to conflicting interpretations. Direct observation by total internal reflection microscopy will clarify the steps in branch formation. Identification of inhibitors will provide a method to verify the role of branching by Arp2/3 complex in vivo. [unreadable] [unreadable]