Bioanalytical techniques and affinity assays for DNA damage and molecular interactions

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This research program will focus on developing analytical techniques and ultrasensitive assays for analysis of minute amounts of DNA damage and for studying interactions involving G-protein-coupled receptors (GPCRs). A variety of endogenous and environmental agents can damage human DNA, leading to various adverse health outcomes. Thus, it is crucial to detect DNA damage. Current immunoassays using antibodies cannot detect multiple types of DNA damage. The proposed research will use DNA repair proteins to recognize and bind to multiple types of DNA damage. Combined with capillary electrophoresis separation and laser induced fluorescence detection, the new affinity assays will enable detection of a wide range of DNA damage that is relevant to environmental, occupational, and clinical exposure, such as UV radiation, cancer treatment drugs, and other environmental carcinogens. GPCRs mediate most of our physiological responses to hormones, neurotransmitters and environmental stimulants. Much effort has been directed to determining structures of GPCRs, but little is understood about the dynamic interactions The proposed research will establish unique laser induced fluorescence polarization assays with capillary electrophoresis separation to study the conformation changes and binding domains of GPCRs interactions with their ligands. These assays and studies are useful to therapeutic development because GPCRs represent the largest class of molecular targets with proven therapeutic value. This research will strengthen our established excellence in bioanalytical chemistry, foster inter-disciplinary collaborations, and train multidisciplinary people to address analytical challenges facing biochemical and environmental studies.