CAREER: Theoretical Approaches to Single-molecule Biophysics

职业：单分子生物物理学的理论方法

• 批准号: 0845099
• 负责人: Olga Dudko
• 金额: $ 79.36万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-15 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0845099&HistoricalAwards=false
• 关键词: CAREER; Theoretical; Approaches; Single; molecule

The objective of this CAREER project is to understand the fundamental physical principles that govern the structure formation and functioning of biological macromolecules at the single-molecule level. The strategy is to use the great explanatory power of non-equilibrium physics to tackle otherwise intractable problems in molecular and cell biology, and conversely to motivate new physical concepts through the exploration of biological processes at the level of individual biomolecules. The research plan includes four interrelated projects: (1) Revealing mechanisms of living cell processes from single-molecule manipulations. The project addresses the challenging task of extracting novel information from experimental outputs. (2) Analyzing the effect of experimental variables on single-molecule manipulations. The project will establish the ways to disentangle the factors in the experimental setup from the information about the biomolecule of interest. (3) Formulating multistate theory of single-molecule force spectroscopy. This project will enable the study and prediction of new phenomena that can emerge at higher levels of complexity. (4) Understanding the role of multidimensional free energy landscapes in the mechanical unfolding of complex biomolecules. This approach will help design experiments that examine secondary and tertiary structure in complicated biomolecules.This research plan will build a foundation for achieving the PI's long-term goals of extending single-molecule biophysical theory to the cellular level and accessing the machinery of a living cell. The foundation for excellence in education will be built upon the following contributions. (1) Incorporating research activities into undergraduate courses, which are designed to mimic the processes an investigator undertakes in writing a publishable research paper and defending the content of their manuscript with peers. (2) Innovations in teaching that have the potential to transform how people learn science. These include the use of Personal Response System clickers, the most powerful and flexible student response system available, as well as making increasing use of computer simulations for creating interactive "virtual" physics experiments. 3) Bringing underrepresented groups into the research pipeline at the undergraduate level. California State University San Marcos will be the lead partner in efforts to extend leading-edge biological physics into the curriculum at teaching universities. As outreach remains a significant challenge for the physics community, advantage will be taken of the widespread interest in living systems to ensure this challenge has been met. The PI believes that biological physics must become a mainstream course in all physics departments. The designed innovative curriculum, integrated with research, training and outreach activities, will enable training of a new cadre of scientists equally competent in advanced physics and computation as in biochemical reactions, experimental protocols and biological databases. This approach will be used as a means to create a national and international awareness of biological physics and physics frontiers research, and to make UCSD the world leader in combining the principles, language and tools of physics with those of biology, so as to engender a revolution in our understanding of living processes. This project is jointly supported by Molecular Biophysics in the Division of Molecular and Cellular Biosciences and by the Physics of Living Systems program in the Physics Division.

该职业项目的目标是了解在单分子水平上控制生物大分子的结构形成和功能的基本物理原理。该策略是利用非平衡物理学的强大解释力来解决分子和细胞生物学中其他棘手的问题，并反过来通过探索单个生物分子水平的生物过程来激发新的物理概念。该研究计划包括四个相互关联的项目：（1）通过单分子操作揭示活细胞过程的机制。该项目解决了从实验输出中提取新信息的挑战性任务。 (2)分析实验变量对单分子操作的影响。该项目将建立将实验设置中的因素与感兴趣的生物分子信息分开的方法。 (3) 建立单分子力谱的多态理论。该项目将能够研究和预测可能以更高复杂程度出现的新现象。 (4)了解多维自由能景观在复杂生物分子的机械展开中的作用。这种方法将有助于设计检查复杂生物分子中二级和三级结构的实验。该研究计划将为实现 PI 的长期目标奠定基础，即将单分子生物物理理论扩展到细胞水平并了解活细胞的机制。卓越教育的基础将建立在以下贡献之上。 (1) 将研究活动纳入本科课程，旨在模仿研究者撰写可发表的研究论文并与同行捍卫其手稿内容的过程。 (2) 教学创新有可能改变人们学习科学的方式。其中包括使用个人响应系统答题器，这是目前最强大、最灵活的学生响应系统，以及越来越多地使用计算机模拟来创建交互式“虚拟”物理实验。 3）将代表性不足的群体纳入本科阶段的研究渠道。加州州立大学圣马科斯分校将成为主要合作伙伴，致力于将前沿生物物理学扩展到教学大学的课程中。由于推广仍然是物理学界的一项重大挑战，因此将利用对生命系统的广泛兴趣来确保应对这一挑战。 PI认为生物物理学必须成为所有物理系的主流课程。设计的创新课程与研究、培训和推广活动相结合，将能够培训一支新的科学家骨干队伍，他们在先进物理和计算、生化反应、实验方案和生物数据库方面同样有能力。这种方法将被用来作为一种手段来提高国家和国际对生物物理学和物理学前沿研究的认识，并使加州大学圣地亚哥分校成为将物理学与生物学的原理、语言和工具相结合的世界领导者，从而在我们对生命过程的理解上引发一场革命。该项目由分子和细胞生物科学部的分子生物物理学和物理部的生命系统物理学项目共同支持。