Photoprocesses in biology are fundamentally necessary for life and include photosynthesis, DNA damage and repair, vitamin D synthesis and vision. My research interests lie in understanding the very fast (ultrafast) dynamics in the fundamental pericyclic, and isomerization reactions underlying these bioprocesses, with nucleic acid damage in particular a recent research focus. We also develop new tools to further probe these processes and increase our understanding of them.
Our approach is to use whatever techniques are best suited for probing the environment and dynamics of biological molecules, usually spectroscopic probes, and then to develop better probes for the specific questions that arise out of these preliminary experiments. Computations are used to direct and refine hypotheses. This unique approach has allowed us to identify and quantify the structural and environmental elements which influence photochemical reactions and photophysical processes of biomolecules. This approach has also allowed us to investigate much bigger questions, such as the origins of molecular life on earth and the molecular basis for cancer. Individual projects and our progress on them are described below.
Nucleic acid excited-state dynamics and photochemistry. Currently, the largest research effort in my group is being devoted to the molecular origins and physiological consequences of the differential response of RNA and DNA to UV light and other environmental agents. While the health consequences of DNA irradiation by UV light are well-known, surprisingly little is known about RNA's response to UV light at either the molecular or cellular levels. Such studies have implications in organic photochemistry, the molecular origins of life and mechanisms for UV-induced disease, such as skin cancer and aging.
Nucleic acid damage detection. We have worked on the development of probes to detect nucleic acid damage, including DNA and RNA molecular beacons, fluorescently labelled hairpins, fluorescent organic and inorganic dyes. These are general, non-destructive, sensitive probes of nucleic acid damage for both in vitro and in vivo applications. The technique is more sensitive, simpler to perform, and more general in the forms of nucleic acid damage detected than current assays. We have also worked on the development of DNA and RNA microplates and microarrays for massively-parallel detection of nucleic acid damage, repair and protection on genome-wide scales. Probing deeper the structural determinants of nucleic acid reactivity provides a greater insight into the molecular factors which determine disease. By providing a platform for a complete survey of nucleic acid genome across the whole organism, causal relationships can be established in such important ailments as cancer, aging, and other DNA damage-related diseases. (Publications 59, 60)
More details and links to papers will be uploaded soon.