This award supports theoretical research at the interface of physics and biology. The goal is to develop statistical physics models of chromosomes in cells that connect their structure to their function. In biology chromosomes are typically described as carriers of genetic information. They are also multi-component and dynamic polymer-like structures made of DNA and proteins that exhibits elements of both regularity and randomness. At the micron scale genes on chromosomes are often localized to particular regions of the cell, within which they undergo diffusive motion. This spatial and temporal organization of chromosomes has been quantitatively characterized using cell biology techniques but the rules that connect these physical properties to their function are largely unknown. The goal of this proposal is to develop coarse grained models based on ideas from statistical physics, which will elucidate the physical mechanisms that link chromosome structure at the micron scale to its function. Two fundamental biological processes will be considered: transcription and DNA recombination. The key question that will be addressed is how these processes are modulated and controlled by the spatial and temporal organization of genomes in cells. One of the key features of the theoretical research supported by this award is a close collaboration with experimental labs that study transcription and recombination quantitatively at the single molecule and single cell level. Theoretical predictions based on specific physical mechanisms of transcription and recombination will be tested in these labs.
This award will support graduate students working at the interface of physics and biology. Physics graduate students engaged in research supported by this award will closely collaborate with biology students in collaborating labs. This mode of graduate training will promote an interdisciplinary research environment that will result in the cross-fertilization of ideas between statistical physics and molecular and cell biology. It will provide physics students with a unique opportunity to learn from students in life-science fields and help train them for research in interdisciplinary teams, which are being deployed with increasing frequency in industry and academia to tackle the outstanding challenges in biology and medicine.
NON-TECHNICAL SUMMARY
Chromosomes are biological structures that perform functions that are essential to life, such as replication of DNA, the repair of damaged DNA, and the synthesis of new proteins. Chromosomes are also large molecular structures consisting of DNA and proteins whose shape and motion within the cell can be described in quantitative details using ideas from physics. The research supported by this award will provide the link between the biological functions of chromosomes and their physical attributes. In particular, it will lead to mathematical descriptions of how the nature of the dynamic and folded state of chromosomes within cells specifies their biological function. A mathematical description will be developed for the search process by which two genes on the same chromosome find each other within the crowded environment of the cell so as to enable the exchange of genetic material that occurs in the process of DNA recombination. Also, there is an abundance of experimental evidence that the folded state of DNA can interfere with the reading of genes in the process of transcription that leads up to protein synthesis, and the proposed research will formulate quantitative models of this unusual structure-function relation. The outcome of these theoretical investigations will be concrete proposals for quantitative experiments on DNA and chromosomes which will be carried out in collaborating biology laboratories that study DNA recombination and transcription. The combined theoretical and experimental approaches will lead to a precise quantitative description of chromosome structure and function.
This award will support graduate students working at the interface of physics and biology. Physics graduate students engaged in theoretical research supported by this award will closely collaborate with biology students. These activities will promote an interdisciplinary research environment that will result in the cross-fertilization of ideas between statistical physics and molecular and cell biology. This environment will also provide the students with a unique opportunity to learn from students in biological fields and help train them for research in interdisciplinary teams which are being deployed with increasing regularity in industry and academia to tackle the outstanding challenges in biology and medicine.
