CAREER: Data-Driven Models for Biological Dynamics

活细胞是一个活跃的环境，大的生物分子(如蛋白质或DNA)在这里运动、碰撞和反应。目前的实验间接观察生命系统中的这些过程，因此，解释间接观察的数据是理解和数学描述细胞内发生的事情的关键挑战。拟议的工作将有助于数量生物学的发展，因为它考虑了如何从目前可用的实验数据中推断出数据驱动的模型。这种建模将产生新的理论框架，以捕捉生物分子的扩散及其波动的形状最终如何维持生命。将开展以生物学和物理学交叉为重点的活动，目的是提高科学素养。将为广大受众开发一门新的生物物理学入门课程，并将开展若干外联活动。本科生和高中生将通过美国化学协会项目种子参与这项研究，特别强调招募女性和来自贫困背景的学生。印第安纳波利斯动物园将举办一个夏令营项目(8-12岁)，主题是“细菌塞伦盖蒂：探索细菌动物群”。该项目有两个总体目标：1)提取单分子构象动力学模型(从单分子力谱)，这将有助于超越马尔可夫模型范式，并表征生物分子的构象记忆，连接新生链中的动力学和功能，在不同条件下折叠的蛋白质，以及活跃的(ATP-水解)马达；2)直接从荧光相关光谱开发数据驱动的框架，用于复杂拥挤的细胞环境中的异常扩散。该奖项由分子和细胞生物科学部的细胞动力学和功能计划以及物理系的生命系统物理计划共同支持。

The living cell is an active environment where large biological molecules (such as proteins or DNA) move, collide and react. Current experiments observe these processes indirectly in living systems and as a result, interpreting data from indirect observation is a key challenge in understanding and mathematically describing what happens inside cells. The proposed work will contribute to the development of quantitative biology by considering how data-driven models can be inferred from currently available experimental data. This modeling will produce novel theoretical frameworks to capture how the diffusion of biomolecules and their fluctuating shapes ultimately sustain life. Activities focused on the intersection of biology and physics will be undertaken with the goal of advancing science literacy. A new introductory course in biophysics will be developed for a wide audience, and several outreach activities will be undertaken. Undergraduate and high school students will be engaged in the research through the American Chemical Society Project SEED, with special emphasis placed on recruiting women and students from underprivileged backgrounds. A Summer Camp Program (for ages 8-12) will be held at the Indianapolis Zoo on the subject "The Bacterial Serengeti: exploring the bacterial fauna". The project has two overall goals: 1) Extracting models of conformational dynamics of single molecules (from single molecule force spectroscopy) that will help go beyond the Markov model paradigm and characterize conformational memory of biomolecules linking dynamics and function in nascent chains, folded proteins under varying conditions, as well as active (ATP-hydrolyzing) motors; 2) Developing data-driven frameworks for intracellular anomalous diffusion in the complex crowded cellular environment directly from fluorescence correlation spectroscopy.This award is supported jointly by the Cellular Dynamics and Function program in the Division of Molecular and Cellular Biosciences and by the Physics of Living Systems program in the Division of Physics.