BME PhD Prospectus Defense - Chris Sloas

  • Starts: 2:30 pm on Tuesday, October 23, 2018

Title: “Engineering Mechanotransduction in Mammalian Cells”

Committee: John T. Ngo, PhD – BU BME (Advisor, Chair); Michael Smith, PhD – BU BME; Mary Dunlop, PhD – BU BME; Stephen Blacklow, PhD – Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology.

Abstract: Mechanical forces in the cellular microenvironment are crucial to differentiation, development, and homeostasis. Furthermore, disrupted mechanical environments are hallmarks of diseases such as fibrosis and atherosclerosis. In order to study mechanobiology, researchers have developed diverse methods to precisely control forces applied to cells. However, there do not yet exist complementary genetic tools to study mechanobiology from the inverse perspective, controlling how cells perceive and respond to these forces. Here, we combine protein engineering, synthetic biology, and single molecule techniques to design novel mechanosensitive proteins that specify how mammalian cells interpret mechanical information at cell-cell and cell-matrix interfaces. We first demonstrate a strategy to engineer genetically encoded tensiometers that respond to tunable levels of force by building upon the Notch mechanoreceptor. We next investigate improvements to synthetic Notch mechanotransduction that can enable ultra-sensitive ligand detection. Lastly, we describe the use of transforming growth factor-β as a modular platform for signaling through mechanosensitive growth factors. Through this study, we will develop a mechanogenetic toolkit that provides a deeper understanding of mechanotransduction design principles and enables controllable force-based signaling for tissue engineering and cell therapy applications.

24 Cummington Mall, room 103

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