This award supports interdisciplinary research and education at the interface of theoretical statistical physics and biology. The Division of Materials Research and the Division of Molecular and Cellular Biology contribute funding to this award.
Biophysical experiments in living cells provide a quantitative description of how the processes of life are orchestrated in space and time. Fluorescence microscopy, quantitative PCR, DNA chips, fluorescence correlation spectroscopy, and many other modern techniques of cellular and molecular biology are being used with increasing regularity to examine viral infection, regulation of gene expression, structure and dynamics of mitotic and interphase chromosomes, cell motility, and the self-assembly of molecular motors. These experiments are often quantitative in nature providing information about the length, time, and energy scales associated with life's processes. At the same time in vitro experiments on purified components are providing an equally quantitative picture of the same processes when isolated from their natural surroundings. The PI to develop a practical theoretical framework for organizing the wealth of quantitative data provided by biophysical experiments in vivo and for reconciling this data with results from in vitro studies. In particular, the PI seeks to develop quantitative models of DNA and chromosome structure in living cells and to understand how physical attributes of DNA play out in transcription, replication, recombination and DNA damage repair. Statistical physics models of polymers will be used to construct effective models for DNA and chromatin in vivo. The central question that PI aims to address is: To what extent can the complexity of the cellular interior be described by a few parameters? For example, in the case of interphase chromosomes in yeast, their structure and dynamics will be considered from the point of view of a polymer confined to the nucleus and tethered at various locations along the nuclear periphery. Comparing the results of theoretical calculations with fluorescence experiments, will lead to the determination of the effective, in vivo, contour length and persistence length for interphase chromosomes. The PI's collaborations enable expermental tests of the central theoretical ideas that will be developed. Physics graduate students working with the PI on the problems outlined in this proposal will closely collaborate with biology students in the three experimental labs thus creating an intellectual environment in which interdisciplinary research will be able to flourish. The proposed research will be tightly coupled to a number of teaching initiatives at the interface of physics and biology. These are the further development of courses for the Biological Physics major at Brandeis, initiated by the PI, as well as completing a textbook on the "Physical Biology of the Cell", which the PI has been writing with collaborators. The PI is taking part in four-month long research rotations which are mandatory for first year graduate students in the Life Sciences at Brandeis. Students doing a rotation with the PI will gain valuable experience in quantitative modeling as practiced by physicists that they can apply in their thesis work and later in their careers as biomedical researchers.
NON-TECHNICAL SUMMARY: This award supports interdisciplinary research and education at the interface of theoretical statistical physics and biology. The Division of Materials Research and the Division of Molecular and Cellular Biology contribute funding to this award.
With the advent of new experimental techniques, there has been a literal explosion of quantitative data on biological systems with the potential to provide insight into the processes of life. The physical sciences are able to make significant contributions to understanding these data. This award supports such research. The PI will apply statistical physics to develop quantitative models of DNA and chromosome structure in living cells with an aim to better understand the role physical attributes of DNA play in cellular processes involving DNA, such as transcription, replication, recombination and DNA damage repair. The research will address the extent to which simplified models can capture the essential physical processes that underlie the function of DNA in various cellular processes.
Physics graduate students working with the PI on the problems outlined in this proposal will closely collaborate with biology students in the three experimental labs thus creating an intellectual environment in which interdisciplinary research will be able to flourish. The proposed research will be tightly coupled to a number of teaching initiatives at the interface of physics and biology. These are the further development of courses for the Biological Physics major at Brandeis, initiated by the PI, as well as completing a textbook on the "Physical Biology of the Cell", which the PI has been writing with collaborators. The PI is taking part in four-month long research rotations which are mandatory for first year graduate students in the Life Sciences at Brandeis. Students doing a rotation with the PI will gain valuable experience in quantitative modeling as practiced by physicists that they can apply in their thesis work and later in their careers as biomedical researchers.
