DNA damage recognition mediated by repair proteins carrying [4Fe4S] clusters and understanding proton-coupled electron transfer processes using a lipid-modified electrochemical platform

Abstract

In my postdoctoral work (Caltech), I unraveled the mechanism by which a collection of DNA-processing proteins contg. redox-active [4Fe4S] metallocofactors detects DNA lesions and upholds genome integrity in a timely and synchronized fashion. DNA damage, as arise with defective repair, lead to cancer. I utilized electrochem., AFM, EPR, UV-Vis, CD, EMSA gel assay, and in vivo growth and rescue assay to understand the signaling and damage detection processes facilitated by [4Fe4S] enzymes with low cellular copy nos. Exptl. and biophys. modeling results validate a DNA damage search mechanism enabled by redox-active [4Fe4S] cluster proteins via long-range DNA-mediated charge transfer that explains the fast lesion detection kinetics obsd. in living organisms. My PhD work (UIUC) includes facilitating and controlling the oxygen redn. reaction by using bio-inspired catalysts and so-called hybrid bilayer membranes (HBMs), which are self-assembled monolayers covered by a lipid layer. The latter work explores how HBMs supported on electrodes can be used to independently control the thermodn. and kinetics of both proton and electron transfer processes in proton-coupled electron transfer reactions and thereby modulate the turover frequency and selectivity of catalysts. Over the course of my academic training and research career, I have published 13 papers (with 6 addnl. manuscripts in prepn.). My interests are broad, but center around self-assembly, electrocatalysis, synthesis, and protein and reaction dynamics. I have always enjoyed opportunities to conduct research that crosses traditional fields of study. My postdoctoral fellowship will end in July 2018 and I am eager and ready to start my independent academic career. Building upon a strong foundation in inorg., anal., and biol. chem., I will devise new methodologies to understand reaction landscape in a complex environment and develop org.-inorg. hybrid platforms to promote efficient catalysis relevant to alternative energy conversion scheme.