A&P Seminar - Katharine White

The Analytical and Physical Seminar Series presents: Katharine White

University of Notre Dame

Host: Lauren Webb

Title: Regulation of cell behaviors by pH: The pluses and minuses of protein electrostatics

Refreshments served at 3:15pm

Location: WEL 2.122

Transient increases in intracellular pH (pHi) are necessary for normal cell processes of cell-cycle progression, migration, and differentiation while dysregulated pHi dynamics are linked to diseases such as neurodegeneration and cancer. While the effects of pHi on global cell behaviors are well established, the proteins and molecular mechanisms that drive these pH-sensitive responses are largely unknown. Furthermore, a lack of tools to directly, specifically, and spatiotemporally manipulate pHi has restricted experiments probing how pH dynamics alter individual cell behaviors. A primary topic of the seminar will be work identifying the molecular mechanisms driving dynamic pH-sensitive functions of both wild-type and mutant proteins. Together, our computational, biophysical, and cellular analyses reveal a conserved role for pHi in regulating function of modular SH2 signaling proteins to drive cell behaviors. Moreover, our data suggest that cancer mutations cluster in these conserved networks to abrogate pH-sensitive regulation of activity and contribute to the hyper-activation of cell signaling in cancer.