April 22, 2015 700 Clark Hall, 4:00 pm
Yimon Aye Cornell University
No more mixed signals: On-demand redox targeting remodels biological stress response
One of the major contemporary challenges in modern cell signaling is to map how specific chemical signal inputs are directly linked to specific biologic signal outputs. Since these responses are dynamical in a cell, ideally, we must understand each process with precise timing. In the emerging field of redox signaling, these challenges are significant because the temporal dynamics of regulated redox responses are critical for complex stage-dependent and gene/pathway-specific physiologic orchestrations—such as cytoprotective responses during embryonic development or in lifespan regulation. General approaches to study redox responses in any living system had been to expose entire specimens to reactive chemical signals. Not only does such a bolus dosing method provide little information on timing and specificity, phenotypic responses from uncontrolled flooding are often linked to oxidative stress instead of physiologic redox signaling. Targeted knockdown approaches are not amenable to studying the precise consequences of redox signaling on demand, and also without perturbing existing protein–protein interactions. The functional redundancies among multiple sites of cysteines render mutagenesis strategies often less tractable in studying gene-specific redox impacts. The Aye laboratory has developed a unique light-activatable chemistry that enables on-target redox stimulation in living systems. The platform pinpoints the consequences of specific redox events against an unmodified background, thereby enabling the reconstruction of individual stress response pathways of importance in physiology and disease states. The talk highlights our early accomplishments, latest results, and future promises in this arena. Host: Warren Zipfel
Biophysics Colloquium chair: Warren Zipfel