CAREER: The Interaction of Ions with DNA: An X-ray Scattering Study

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Two of the most important molecules of life, DNA and RNA, are uniformly negatively charged. Nature takes advantage of the strong interactions between charged particles (e.g., the strong attraction of particles with opposite charges or repulsion of the ones with like charges), to control the shape and function of these nucleic acids. This research project uses x-ray scattering, a newly demonstrated experimental technique, to address fundamental questions about the interaction of positively charged counter-ions with negatively charged nucleic acids. To maintain electrical neutrality in solution, DNA is associated with positively charged partners ranging from small ions to large proteins. Numerous biological processes, including gene regulation and DNA repair, are regulated by the interactions of DNA with charged molecules. These strong interactions are also exploited in the design of pharmaceuticals, small molecules that target and modify DNA. This importance of DNA-charge interactions provides strong motivation for fundamental studies of the properties of these systems. This experimental project is designed to probe these interactions using model DNA systems. This work builds on recent experiments performed at the Cornell High Energy Synchrotron Source in which anomalous small angle x-ray scattering was used to distinguish the scattering signature of a single ionic species (e.g. Rb counterions) from all other atoms/ions in a multi-component system (e.g. DNA in a solution of RbCl). These preliminary measurements enabled unprecedented, quantitative measurements of the spatial distributions of these counterions around the DNA. This project will provide new data to rigorously test conflicting theoretical models of the pertinent interactions. The long-term goal of this project is to exploit this new technology to address biologically relevant questions, such as the role of charged ligands in facilitating attractive forces between DNA strands. This attraction is of fundamental importance to our understanding of how DNA is packaged and stored in our cells. Broader Impacts: This work will have impact in a number of arenas linked together by the theme of promoting interdisciplinary work to a wide audience. The activities range from participation in K-12 outreach through the development of a program to establish a pipeline from predominantly female undergraduate institutions to the Applied Physics graduate program. A successful pilot version of this pipeline program will serve as a model for future efforts. In addition, an Engineering Distribution course will be developed for Cornell undergraduates. The course focuses on interdisciplinary science by introducing important, current topics in molecular biology to students of engineering and physical sciences. Research and Education will be integrated through this course by introducing three new modules. These modules are inspired by the proposed research program and leverage on Cornell's unique research facilities.