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）在其中移动，碰撞和反应。目前的实验在生命系统中间接观察这些过程，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定量生物学的发展，考虑如何从目前可用的实验数据推断数据驱动的模型。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，目标是提高科学素养。将为广大受众编制一个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学会SEED项目参与研究，特别强调招募来自贫困背景的妇女和学生。夏令营计划（8-12岁）将在印第安纳波利斯动物园举行，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（从单分子力光谱学），这将有助于超越马尔可夫模型范式和表征生物分子的构象记忆连接动力学和功能的新生链，折叠蛋白质在不同的条件下，以及活性（ATP水解）马达; 2）开发数据-在复杂拥挤的细胞环境中，直接从荧光相关光谱中获得细胞内异常扩散的驱动框架。该奖项由细胞动力学和功能计划共同支持在分子和细胞生物科学部和物理学部的生命系统物理学计划。

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.