Camille and Henry Dreyfus Professor of Chemistry (b. 1947)
Principal Research Interests
My laboratory investigates the structure and function of biological systems using many tools and methods, always with a strong physical perspective. Four interconnected themes are being pursued.
First, we are broadly interested in electrostatics in proteins and how electrostatics affect function. Our current work uses vibrational probes whose sensitivity to electric fields can be calibrated by Stark spectroscopy. Probes are introduced on inhibitors, by modification of amino acids and by incorporation of unnatural amino acids, and these are used to map electric fields for comparison with simulations and as probes of the role of protein electrostatics in enzymatic catalysis.
Second, we use supported lipid bilayers as mimics for cell surfaces and as tools in biotechnology. A broad vision is to engineer interfaces between hard surfaces and soft materials, ultimately leading to sophisticated biocompatible interfaces that can be used to control, interrogate or organize complex living systems. Recent work addresses the formation of domains and protein associations with these domains, interactions of DNA, proteins and cells with supported bilayers, and the mechanism of vesicle fusion. This work has motivated the development of advanced optical microscopy methods for probing the interface between membranes on solid supports and cell membranes. A novel type of imaging mass spectrometry is being applied to characterize the lateral organization and composition of bilayers and associated membranes with 50 nm resolution.
Third, we have a long-standing interest in the mechanism of light-driven, long-distance electron transfer in photosynthetic reaction centers, one of the fastest known reactions. This is being studied by femtosecond fluorescence and transient absorption spectroscopy, site-specific mutagenesis and vibrational Stark spectroscopy.
Fourth, related methods are also being used to probe excited state dynamics, solvation, and electronic structure in variants of green fluorescent protein (GFP), widely used in cell biology. Recent work focuses on discoveries of photo-association and -dissociation of split GFPs that can be used to modulate complex functions using light, novel GFPs with alternative folds, and the mechanism(s) of ground and excited state proton transfer.
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