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The objectives of my research reflect my interests in inorganic chemistry, biochemistry and biophysics. Using an integrative approach, I plan to utilize protein design to create simple model systems that provide insights into the functioning of more complex biological systems. One objective is to study biological membrane fusion, a process required for viral infection, intracellular transport and neurotransmitter release. Small protein domains that can bind to helical membrane fusion proteins and inhibit fusion will be designed as tools for studying membrane fusion, and as possible antiviral agents against HIV, influenza, etc. Another research objective is to probe the molecular basis of gene regulation and DNA repair through the design of small protein domains that can bind specifically to particular portions of DNA, allowing us to control gene expression through binding or chemical modification. A third interest in the lab is the design of small metal-binding domains as models for naturally occuring metalloproteins. Two specific targets include the metalloregulatory protein merR which binds mercury and is involved in heavy metal detoxification in bacteria, and the Zn-containing Ada demethylase, which repairs methylation damage in E. coli.
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