9734178 Marko This is a CAREER award integrating research and education which is jointly funded by the Divisions of Materials Research, Physics, Molecular and Cellular Biology and the Mathematical and Physical Sciences Directorate Office of Multidisciplinary Activities. The grant involves teaching and research on the application of condensed matter physics to problems in molecular and cell biology. In the past fifty years biology has largely become based on the physical science of organic molecules. This understanding has largely been the domain of (bio)chemistry. However, with the advent of new tools that allow us to manipulate large protein, RNA and DNA molecules, biochemists and biologists are being faced with a new class of problems related to the physical chemistry of huge macromolecules. There has been tremendous progress in our understanding of the statistical physics of large molecules in the past two decades. However, even the basic ideas from polymer science are largely unknown to biologists, and even to most biochemists. Further, while in principle useful, much of polymer statistical mechanics is ill-adapted for application to biopolymers. Most of polymer physics is aimed at homopolymers or large-block copolymers subject to relatively weak physical interactions on the scale of kT; by contrast biopolymers are almost always heteropolymers whose function is defined by their sequence, and their functions often involve interruption of chemical bonds characterized by eV energies. This research will attempt to fill the gap between polymer science and molecular biology using a two-pronged teaching and research approach. In the classroom, a cross- disciplinary course will be developed aimed at undergraduates in both physics and biology. This course will be integrated with a laboratory which will provide hands-on experience with measurements of motion and forces at the sub-cellular level. Lab projects will include analysis of microtubule dynami c instability, study of elastic response of vesicles, study of cell and organelle motility in cell cultures, and physical properties of single DNA molecules; they will all involve quantitative analysis of video microscopy data. This will introduce physics students to exciting research possibilities which are developing in the field of molecular biophysics, and at the same time can provide some basic background in polymer physics to biology students. The research program complements the course development by focusing on theoretical descriptions of test tube experiments on biomolecules, and the extension of those descriptions to activity of biomolecules in living cells. The main interest is on the interaction of DNA molecules with one another, and with enzymes which modify DNA structure. The long term goal is a theoretical understanding of the enzyme systems which regulate the structure and topology of prokaryote and eukaryote chromosomes. The main question is how do cells duplicate, recombine and segregate their centimeter-long genomic DNA's without fatal entanglements or breakages. %%% This is a CAREER award integrating research and education which is jointly funded by the Divisions of Materials Research, Physics, Molecular and Cellular Biology and the Mathematical and Physical Sciences Directorate Office of Multidisciplinary Activities. The grant involves teaching and research on the application of condensed matter physics to problems in molecular and cell biology. ***
