Quantifying Single Molecule DNA-ligand Interactions

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The objective of this project is to develop single molecule manipulation methods for the quantitative study of DNA-ligand interactions and to use these methods to investigate specific biologically important interactions. In addition to method development, this work will shed light on important problems ranging from the fundamental biophysics of DNA-small molecule interactions to the biophysical and biochemical mechanisms of complex protein interactions involved in DNA replication and recombination. The following three specific aims will be addressed to accomplish the above goals. 1. To probe the biophysical mechanism of DNA-small molecule interactions using DNA stretching. 2. To probe the binding mechanism of single-stranded DNA binding proteins, which are essential components of DNA replication. 3. To investigate the role of important DNA replication and recombination proteins from the bacteriophage T4 system. The PI has developed innovative biophysical methods for examining DNA binding in exquisite detail using single molecule manipulation. The results will have a significant impact beyond this field; as such methods may be adapted to examine a wide variety of important biological systems. The PI also has a strong track record of training graduate and undergraduate students in interdisciplinary research at the interface of physics, chemistry, and biology, including active collaborations with minority-serving and undergraduate institutions. The broader impacts of this research also extend into the classroom, where the PI has developed a new Advanced Physics Laboratory course, which contains several advanced research level experiments, including the use of optical tweezers and atomic force microscopy. Experiments developed by the PI are made publicly available for use by scientists at other institutions. The PI also makes significant contributions to undergraduate teaching, bringing examples from his research into the classroom in courses such as Physics for Pharmacy and Physics for the Life Sciences. This project is supported by the Molecular Biophysics Program in the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences and the Division of Physics in the Mathematical and Physical Sciences Directorate.