Jan 7, 2016
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| Carolyn Hoff Lynch RoomFor inquiries contact Camille Pride at campride@sas.upenn.edu Title: Cytoskeletal structural plasticity in force generation and mechanosensation Abstract: Cytoskeletal filaments play a central role in the generation and transmission forces essential to fundamental biological processes including cell division, differentiation, and morphogenesis, and their dysfunction in disease states such as cancer. Utilizing structural studies with cryo-electron microscopy and complimentary biophysical / cell biological approaches, we aim to uncover the detailed mechanisms of the macromolecular interactions which orchestrate these events. At the molecular level, they are driven by conformational changes in the component proteins of these filaments, tubulin and actin, as well as their binding partners. I will discuss my previous studies of the GTP hydrolysis-dependent conformational cycle underlying microtubule dynamic instability, which is critical for generating forces to segregate chromosomes during mitosis and is the target of several chemotherapeutic drugs. I will then focus on our ongoing efforts to visualize conformational changes in actin filaments and closely associated binding partners key for both generating forces (myosin motor proteins) and sensing forces (adhesion proteins and, provocatively, actin filaments themselves) to facilitate mechanotransduction. By dissecting the detailed molecular mechanisms of mechanosensation pathways, our long-term aim is to develop novel targets for therapeutic intervention in cancer metastasis and regenerative medicine.
