Biochemistry Seminar

http://chemistry.cornell.edu/yimon-aye

Precisely timed and spatially regulated electrophilic chemical signals are the essence of biochemical redox signaling. However, defining the precise biological impacts of localized signals that engage with specific protein targets under physiologic conditions has proven to be highly challenging. This talk presents a unique set of proximity-directed chemical tools that enables powerful interrogation into functional consequences of specific redox events through precision electrophile targeting in living systems. With this in vivo-validated redox-targeting toolset, we identify bona fide "first responders" that interact with native signaling electrophiles under electrophile-limited (true k_cat/K_m) conditions. Our data illuminate these first responders as novel signaling nodes, interchanging electrophile and conventional signaling codes such as phosphate and ubiquitin for decision making at organismal level. Our unique chemical biology toolset sets the stage for ruling in gain-of-function (or dominant loss-of-function) electrophilic modifications and relating them to phenotype in an unbiased experiment that is not hampered by functional redundancy. The NSF CAREER, NIH Director's New Innovator, Beckman Young Investigator, Office of Naval Research Young Investigator, Pershing Sohn Prize, and Sloan Fellowship programs are acknowledged for research support.