Collaborative Research: Maximum Caliber: An Approach to Modeling Stochastic Dynamics in Biology.

这个跨学科的项目将开发一种称为最大口径(MaxCal)的非平衡物理原理。MaxCal提供了一种建立动力学模型的通用方法，特别是在涨落很重要的情况下，如单分子和少粒子系统。这个项目的重点是开发更好的动力学模型，以应用于分子和细胞生物物理学。MaxCal将用于分析遗传触发开关、遗传计时器、三基因抑制电路，以及研究具有激活和抑制功能的合成遗传振荡器-枯草杆菌ComK基因调控反馈系统。还将研究一种从单分子噪声数据中识别隐藏的动力学状态的方法。PI将与他的实验合作者迭代，以测试和推进MaxCal，激励新的实验，并开发对这些复杂系统的原理的见解。因此，该项目将促进对快速增长的实验数据的分析，以及合成生物学家的电路设计。MaxCal的原理具有广泛的用途：从纳米结构和纳米发动机设计到对神经系统、生态学、车辆交通、经济物理学和星际化学的建模。该项目将影响多个外展工作和新的协作/教育中心。劳弗中心和丹佛大学MCB项目的研究生和博士后将接触到MaxCal和生物学中正在开发的随机物理。这项提案中的MaxCal应用程序将被纳入未来版本教科书(用于全球150门研究生和本科生课程)的NESM章节(S)，该教科书由PI与Sarina Bromberg共同编写。除了在这个项目中培训博士后和研究生，每年至少有一名本科生将接受培训，作为他们荣誉论文的一部分，这是丹佛大学物理和天文学系的一项要求。PI还将在劳弗中心接待高中生，向他们介绍大学研究，延续他在加州大学旧金山分校开创的传统。MaxCal项目还将通过让加州大学伯克利分校、亚利桑那州立大学和德克萨斯大学西南医学中心的合作者的人员参与，为更广泛的教育做出贡献。PI将在劳弗中心的网络服务器上免费提供计算机代码，以供更广泛的使用。该项目由物理部的生命系统物理学项目和分子和细胞生物科学部的分子生物物理学项目共同支持。

This interdisciplinary project will develop a principle of nonequilibrium physics called Maximum Caliber (MaxCal). MaxCal offers a general way to make dynamical models, particularly where fluctuations are important, as in single-molecule and few-particle systems. This project focuses on developing better kinetic models for applications in molecular and cellular biophysics. MaxCal will be applied to analyze a genetic toggle switch, a genetic timer, a three-gene repressilator circuit, and studies of a synthetic genetic oscillator with activation and repression, the B. Subtilis ComK gene regulatory feedback system. A way to identify hidden kinetic states from single molecule noisy data will be investigated as well. The PI will iterate with his experimental collaborators to test and advance MaxCal, motivate new experiments and develop insights into the principles governing these complex systems. Thus this project will facilitate the analysis of the rapidly growing body of experimental data, as well as circuit design by synthetic biologists. The principles of MaxCal have broad utility: from nano-structures and nano-motor design to modeling neural systems, ecology, vehicular traffic, econophysics and interstellar chemistry. The project will impact multiple outreach efforts and new centers for collaboration/education. Graduate students and post docs in the Laufer Center and in the University of Denver's MCB program will be exposed to MaxCal and the stochastic physics in biology that are under development in this project. MaxCal applications from this proposal will be incorporated in the NESM chapter(s) of future editions of the textbook (used in 150 graduate and undergraduate courses worldwide) Molecular Driving Forces that the PI co-authors with Sarina Bromberg. Besides training post docs and graduate students in this project, at least one undergraduate student every year will be trained as part of their honors thesis, a requirement in the department of Physics and Astronomy at the University of Denver. The PI will also host high school students at Laufer Center to introduce them to university research, continuing the tradition he initiated at UCSF. The MaxCal project will also contribute to broader education by involving personnel from collaborators at the University of California, Berkeley; Arizona State University; and the University of Texas Southwestern Medical Center. The PI will make the computer codes freely available on the Laufer Center web server for broader usage.This project is being supported jointly by the Physics of Living Systems Program in the Physics Division and by the Molecular Biophysics Program in Division of Molecular and Cellular Biosciences.