The Division of Materials Research and the Division of Molecular and Cellular Biology jointly fund this award. It supports theoretical research and education at the interface of condensed matter physics and biology. The PI aims to illuminate the workings of three paradigmatic molecular devices through the analysis of experiments performed by collaborators. o DNA loop formation mediated by repressors such as LacI and GalR is an important mode of bacterial gene regulation. Recent and pending experiments on the effect of direct physical manipulation on loop formation will yield insight into the structure of the "repressosome" complex. Analysis will be performed by a combination of transfer-matrix and other methods. o Gene transcription is widely believed to create torsional stress in DNA. The resulting torsional stress can in turn affect the transcription of nearby genes, induce structural transitions in the DNA, and perhaps even assist the disassembly of nucleosomes downstream of the polymerase. New experiments directly demonstrate torsional stress by using recombinase to clip out supercoiled segments from a transcribing, linear DNA construct. These experiments will be analyzed to confirm their interpretation, and to access experimentally the free energy of supercoiling and compare it to earlier predictions. o The ribosome remains the Everest of molecular machines, despite spectacular progress in determining its structure. Experiments now underway will determine the effects of physical forces on the speed of ribosome translation. The analysis of these experiments involves entropic forces. Required analytic tools will be constructed and used to help interpret the experiments. In addition, the PI will characterize the material properties of a recently discovered DNA conformation, left-handed "L-DNA" created when B-form is stretched and undertwisted. Teaching and outreach: Extending the PI's undergraduate course and textbook in ways that have been requested by users of the preliminary versions helps integrate research and education. The work will be distributed electronically in the form of additional draft chapters of the book. Other projects will be undertaken to help a broader group of instructors to create courses in biological physics. Material created in the course, including classroom demonstrations, will also enter into the PI's lectures to high school students at Penn's Summer Science Academy. The proposed work will also give one graduate student interdisciplinary training leading to a Ph.D. Broader impact: Yesterday's discovery is today's tool. The development of techniques for the manipulation and interrogation of single biomolecules has led to an era in which these techniques can be used to extract lessons about the mechanisms of molecular machines and other nanoscale devices used in living cells. For example, this research will forge links between the micrometer world of optical manipulation and the nanometer world of molecular machines by determining the stresses (stretching force and torque) on molecules in terms of the observed or controlled conditions on the ends of the long tethers used to manipulate them. The educational component of the project will contribute to the education of scientists trained in both biological and physical techniques by extending the PI's prior work to create and disseminate both graduate and undergraduate courses on biological physics. %%% The Division of Materials Research and the Division of Molecular and Cellular Biology jointly fund this award. It supports theoretical research and education at the interface of condensed matter physics and biology. The PI aims to use methods of theoretical condensed matter physics to illuminate the workings of molecular devices relevant to biological cell function and physical aspects of genetic regulation. New experimental techniques have opened a window into the materials properties of individual biological molecules and have enabled the building of links between the structure of biomolecules and the actual function of molecular devices. This research will involve close work with experimentalists and the analysis of experiments on biomolecular devices performed by the PI's collaborators. Teaching and outreach: Extending the PI's undergraduate course and textbook in ways that have been requested by users of the preliminary versions will help integrate research and education. The work will be distributed electronically in the form of additional draft chapters of the book. Other projects will be undertaken to help a broader group of instructors to create courses in biological physics. Material created in the course, including classroom demonstrations, will also enter into the PI's lectures to high school students at Penn's Summer Science Academy. The proposed work will also give one graduate student interdisciplinary training leading to a Ph.D. Broader impact: Yesterday's discovery is today's tool. The development of techniques for the manipulation and interrogation of single biomolecules has led to an era in which these techniques can be used to extract lessons about the mechanisms of molecular machines and other nanoscale devices used in living cells. For example, this research will forge links between the micrometer world of optical manipulation and the nanometer world of molecular machines by determining the stresses (stretching force and torque) on molecules in terms of the observed or controlled conditions on the ends of the long tethers used to manipulate them. The educational component of the project will contribute to the education of scientists trained in both biological and physical techniques by extending the PI's prior work to create and disseminate both graduate and undergraduate courses on biological physics. ***
