CAREER: Integrated Teaching and Research on Molecule and Cell Biophysics

这是一个综合研究和教育的职业奖，由材料研究部、物理部、分子和细胞生物学部以及多学科活动的数学和物理科学理事会办公室共同资助。该资助涉及凝聚态物理在分子和细胞生物学问题中的应用的教学和研究。在过去的五十年里，生物学在很大程度上以有机分子的物理科学为基础。这种理解在很大程度上属于（生物）化学领域。然而，随着新工具的出现，使我们能够操纵大的蛋白质、RNA和DNA分子，生物化学家和生物学家正面临着一类与巨大大分子的物理化学有关的新问题。在过去的二十年里，我们对大分子统计物理学的理解有了巨大的进步。然而，即使是聚合物科学的基本思想，生物学家，甚至大多数生物化学家，在很大程度上也是未知的。此外，尽管高分子统计力学在原则上是有用的，但它在生物高分子上的应用并不适用。大多数聚合物物理学都是针对均聚物或大嵌段共聚物的，它们在kT尺度上的物理相互作用相对较弱；相比之下，生物聚合物几乎都是异聚物，其功能由其序列决定，其功能通常涉及以eV能量为特征的化学键的中断。本研究将尝试用双管齐下的教学和研究方法来填补高分子科学和分子生物学之间的空白。在课堂上，将针对物理学和生物学的本科生开设跨学科课程。本课程将与实验室相结合，该实验室将提供亚细胞水平运动和力测量的实践经验。实验室项目将包括微管动力学不稳定性分析、囊泡弹性响应研究、细胞培养中细胞和细胞器运动研究以及单个DNA分子的物理性质；它们都将涉及视频显微镜数据的定量分析。这将向物理专业的学生介绍分子生物物理学领域正在发展的令人兴奋的研究可能性，同时也可以为生物专业的学生提供一些高分子物理的基本背景知识。该研究计划通过关注生物分子试管实验的理论描述以及这些描述在活细胞中生物分子活动的扩展来补充课程发展。主要的兴趣是DNA分子之间的相互作用，以及与修饰DNA结构的酶的相互作用。长期目标是对调节原核生物和真核生物染色体结构和拓扑结构的酶系统的理论理解。主要的问题是细胞如何复制、重组和分离它们的厘米长的基因组DNA，而不会造成致命的缠结或破坏。这是一项综合研究和教育的CAREER奖，由材料研究部、物理部、分子和细胞生物学部以及多学科活动数学和物理科学理事会办公室共同资助。该资助涉及凝聚态物理在分子和细胞生物学问题中的应用的教学和研究。＊＊＊

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. ***