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

这个跨学科的项目将开发一个名为最大口径（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，特别是在波动很重要的情况下，如单分子和少粒子系统。该项目的重点是开发更好的动力学模型，用于分子和细胞生物物理学。MaxCal将被应用于分析遗传拨动开关、遗传计时器、三基因阻遏电路以及具有激活和阻遏的合成遗传振荡器B的研究。亚克隆ComK基因调控反馈系统。一种方法来识别隐藏的动力学状态，从单分子噪声数据也将进行研究。 PI将与他的实验合作者一起测试和推进MaxCal，激励新的实验，并深入了解这些复杂系统的原理。因此，该项目将有助于分析快速增长的实验数据，以及合成生物学家的电路设计。MaxCal的原理具有广泛的实用性：从纳米结构和纳米电机设计到神经系统建模，生态学，车辆交通，经济物理学和星际化学。该项目将影响多个外展工作和新的合作/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MaxCal和本项目正在开发的生物学随机物理。本提案中的MaxCal应用程序将被纳入PI与萨里纳布朗伯格共同撰写的《分子驱动力》教科书（用于全球150门研究生和本科生课程）未来版本的NESM章节中。除了在这个项目中培训博士后和研究生外，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要求。PI还将在劳弗中心接待高中生，向他们介绍大学研究，继续他在UCSF发起的传统。MaxCal项目还将通过让来自加州大学伯克利分校、亚利桑那州立大学和得克萨斯大学西南医学中心的合作者的人员参与进来，为更广泛的教育做出贡献。PI将在Laufer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。该项目由物理学部的生命系统物理学计划和分子和细胞生物科学部的分子生物物理学计划共同支持。

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.