Inferring the Physics of Living Systems from Dynamic Light Microscopy Data

在这个项目中，PI将研究收缩肌动蛋白网络在驱动果蝇胚胎形状变化和形态发生中的作用。收缩肌动蛋白网络越来越多地被证明在包括细胞分裂和胚胎发生在内的细胞运输的基本生物学过程中起着核心作用。提出了一种基于物理的方法，将荧光显微镜数据的定量分析与机制、基于物理的建模相结合，以研究这些过程。这种数据驱动的建模方法带来的一个主要挑战是对相互竞争的物理模型进行公正的评估。为了应对这一挑战，我们探索了一个贝叶斯推理框架，该框架在数据生成过程中对噪声进行建模，以系统地测试传输机制的相互竞争的假设。该研究项目的具体贡献包括对动态、收缩的肌动蛋白网络如何在包括细胞分裂和胚胎发生在内的基本生物过程中运输细胞器和整个细胞进行统一的物理理解。此外，一种数据驱动的方法将基于物理的传输模型与荧光显微镜数据集连接起来，这将对生物物理社区具有广泛的实用性。收缩肌动蛋白网络是存在于真核细胞中的蛋白质网络，在细胞分裂、细胞运动和组织发育中起重要作用。然而，对于肌动蛋白在亚细胞尺度上的短时间尺度动态收缩如何机械地相互作用以协调更大长度和时间尺度上的细胞运输，尚不存在机械的、物理的理解。解决这一机制需要一种定量的、基于物理的方法，在从单个细胞到细胞集合的多个尺度上模拟收缩驱动的运输。目前的项目处于这一研究领域的前沿，这对我们科学地理解收缩肌动蛋白网络在发育中的作用具有重要意义。PI正在推进的教育计划包括加强本科和研究生课程，包括在生物工程系、物理生物学系开设新的研究生选修课，以及在麻省理工学院举办新的全学院范围的生物物理学系列研讨会。作为目前研究项目的结果，PI正在建立一个网络服务器，用于客观的，贝叶斯分析运输测量，以推断各种科学学科中的物理运输模型，更新一个网络服务器，用于将基于物理的建模集成到蛋白质的分子动画，蛋白质组装和细胞骨架动力学中，用于教育目的，并为City ona Hill的学生开发一个分子和细胞生物物理学虚拟实验室。波士顿地区一所为少数族裔服务的当地特许高中。PI的教育和研究活动将通过不断轮换来自本科生生物工程研究经验项目和麻省理工学院本科生研究机会项目的本科生以及来自发展中国家的本科生来进一步传播。

In this project the PI will investigate the role of contractile actin networks in driving shape changes and morphogenesis in Drosophila embryos. Contractile actin networks are increasingly being shown to play a central role in fundamental biological processes involving cellular transport including cell division and embryogenesis. A physics-based approach that integrates quantitative analysis of fluorescence microscopy data with mechanistic, physics based modeling is proposed to investigate these processes. A major challenge posed by this data-driven modeling approach is the unbiased evaluation of competing physical models. To meet this challenge, a Bayesian inference framework is explored that models noise in the data generation process to systematically test competing hypotheses of transport mechanisms. Specific contributions of this research project include a unified, physical understanding of how dynamic, contractile actin meshworks operate to transport organelles and entire cells during basic biological processes including cell division and embryogenesis. Further, a data-driven approach to bridging physics-based transport models with fluorescence microscopy data sets is explored that will be of broad utility to the biological physics community. Contractile actin networks are protein networks present in eukaryotic cells that play an important role in cell division, cell movement, and tissue development. However, a mechanistic, physical understanding of how short time-scale, dynamic contractions of actin at the subcellular scale interact mechanically to coordinate cellular transport at larger length and time-scales does not exist. Resolving this mechanism requires a quantitative, physics-based approach that models contraction-driven transport at multiple scales ranging from single cells to collections thereof. The present project is at the forefront of this research area, which is of great importance to our scientific understanding the roles of contractile actin networks in development. Educational initiatives being advanced by the PI include undergraduate and graduate curriculum enhancement, including the new graduate elective offered in the Department of Biological Engineering, Physical Biology, and a new Institute-wide seminar series in Biophysics at MIT. As a result of the present research project, the PI is establishing a webserver for objective, Bayesian analysis of transport measurements to infer physical transport models in a variety of scientific disciplines, updating a webserver for integration of physics-based modeling into molecular animations of proteins, protein assemblies, and cytoskeletal dynamics for educational purposes, and developing a virtual laboratory in molecular and cellular biophysics for students at City on a Hill, a local charter high school serving under-represented minorities in the Boston area. Educational and research activities of the PI will be further disseminated via continuous rotation of undergraduate students from the Biological Engineering Research Experience for Undergraduates program and MIT's Undergraduate Research Opportunities Program, as well as from developing foreign countries.