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General Area:
My laboratory's research is focused on the dynamics and kinetics of protein-induced, conformational changes in DNA and the structures of nucleo-protein assemblies relevant to transcriptional regulation. We use single molecule experimentation, in particular the tethered particle motion technique with and without magnetic tweezers. We also use scanning force microscopy in collaboration with David Dunlap in the Cell Biology Department.
Current Projects: The λ switch is the most well studied example of a genetic switch in nature. It determines the fate of E. coli bacteria which have been infected by the bacteriophage λ. Upon infection, the newly injected viral DNA can either integrate in the bacterial genome and be passively replicated with it or it can circularize and be actively replicated. In the first case, the virus will be quiescent, until an external event triggers it, in the second case it will cause the lysis and death of the bacteria. What determines the choice between these two behaviors is mostly the λ repressor protein, which recently has been discovered to mediate the formation of a large stable loop in the DNA that effectively represses the lytic genes. We are interested in studying the molecular mechanism at the basis of this switch; this involves understanding the exact role of the λ repressor protein molecules participating in the DNA loop, and characterizing the kinetics and thermodynamics of loop formation and breakdown. Furthermore, we are interested in studying the interplay between DNA looping and supercoiling, which contributes to transcriptional regulation. Instrumentation Development: We are developing a novel single molecule microscope that will allow simultaneous observation of DNA conformations and protein activity. We are interested in understanding how certain motor enzymes are affected by protein-induced DNA conformational changes. We believe that single molecule experiments can provide a unique look into the molecular mechanisms responsible for transcriptional regulation. Theory: We formulate computational and analytical models, which are necessary to validate, explain and interpret the experimental data. Website: www.physics.emory.edu/faculty/finzi/
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