Stochastic Transport in Biology: From Molecules to Ecosystems

智力优势：传输现象与生物组织的所有层次有关，并且跨越了许多数量级的长度和时间尺度。这一范围的一端是分子过程，如离子在细胞膜上的运输；另一端是鸟类和动物在大陆间的迁徙。这些现象的一个共同特征是它们本质上的随机（随机）特征以及它们发生的结构复杂和动态环境。单细胞生物在寻找有利条件时的运动依赖于随机的分子水平，受体结合事件来决定它在每个时刻的运动方向，这给它的整体轨迹带来了随机性。因此，分子水平上的随机性产生细胞水平上的随机性。此外，动态环境的复杂性导致了令人惊讶的运输行为。这样的观察结果提出了一个假设，即在一个组织水平上的随机过程可以以可预测的方式在更高组织水平上的随机输运现象中表现出来。本项目将建立一个基于扩散物理学的通用理论框架，在生物组织的三个不同层次上研究这些思想。在分子水平上，本项目将探索随机性如何影响分子马达驱动蛋白的运输，以及多个马达拉动相同的超分子货物的集体运输行为。在细胞水平上，该项目将描述沿着细胞骨架网络在细胞中进行的由马达驱动的货物运输，这些网络最初被认为是静态的，或者更现实地说，是随着时间尺度的变化而变化的，与运输过程本身相当。最后，在多细胞水平上，本项目将开发模型，探索细胞通信和空间复杂性在蓝藻多细胞群落向光源移动的运输驱动模式形成中的作用。更广泛的影响：对分子、细胞和多细胞组织水平上运输的基本物理的基本理解将对生物研究和生物技术具有广泛的意义，特别是对运输过程的优化设计和控制。此外，本研究产生的一般理论将对动态计算机网络上的信息传递和路由问题以及大规模动态生态和人类网络上的人口扩散问题产生影响。PI和联合PI还将在其机构内和当地区域开展各种外联活动。PI将继续为生物科学专业的学生开发和教授一套成功的、创新的、以微积分为基础的、新生水平的物理课程，该课程使用生物实例来激发和说明物理概念。随着新的计算实验室和基于flash动画的互动网站的增加，课程将进一步发展，使学生能够在计算机上探索物理概念及其生物联系。PI将与当地社区大学合作，培训教师使用这些新教材，这些教材旨在为生命科学入门课程增加一个令人兴奋的、定量的重点。额外的外展活动以当地高中为目标，并与联合项目合作，在湾区的高中开展活动，特别是针对妇女和社会经济背景较差的学生。

Intellectual Merit: Transport phenomena are relevant to all levels of biological organization and span length and time scales ranging over many orders of magnitude. Examples on one end of this range are molecular processes such as the transport of ions across cellular membranes and on the other end, migrations of birds and animals over inter-continental distances. A common feature of these phenomena is their intrinsically stochastic (random) character and the structurally complex and dynamic environments in which they occur. A single-celled organism moving in search of favorable conditions relies on stochastic molecular-level, receptor-binding events to determine its direction of motion at each moment, which introduces randomness to its overall trajectory. Thus, randomness at the molecular level produces randomness at the cellular level. Furthermore, the complexity of dynamic environments leads to surprising transport behaviors. Such observations suggest the hypothesis that stochastic processes at one level of organization can manifest themselves in stochastic transport phenomena at higher levels of organization, in predictable ways. This project will develop a versatile theoretical framework, based on the physics of diffusion, to investigate these ideas at three distinct levels of biological organization. At the molecular level, this project will explore how stochasticity influences transport by the molecular motor kinesin and also the collective transport behavior of multiple motors pulling the same supra-molecular cargo. At the cellular level, the project will characterize the motor-driven transport of cargo across the cell along cytoskeletal networks which, to first approximation, are considered static or, more realistically, are changing over timescales comparable to the transport process itself. Finally, at the multi-cellular level, this project will develop models to explore the role of cellular communication and spatial complexity in transport-driven pattern formation in multi-cellular communities of cyanobacteria moving toward a light source. Broader Impacts: A fundamental understanding of the basic physics of transport at the molecular, cellular and multi-cellular levels of organization will have broad significance for biological research and biotechnology, in particular for the optimal design and control of transport processes. In addition, the general theories arising from this research will have implications for such problems as information transfer and routing on dynamic computer networks and the spreading of populations on large-scale, dynamic ecological and human networks. The PI and Co-PI will also engage in a variety of outreach activities within their institutions and in the local region. The PI will continue to develop and teach a successful and innovative calculus-based, freshman-level physics sequence for biological science majors, that uses biological examples to motivate and illustrate physical concepts. The course will be further developed with the addition of new computational labs and a flash-animation based, interactive website that allows the students to explore physical concepts and their biological connections on their computers. The PI will partner with local community colleges to train instructors in the use of these new course materials, which are designed to add an exciting, quantitative focus to the introductory life science curriculum. Additional outreach activities are targeted at local high schools and, in conjunction with the Co-PI, at high schools in the Bay Area, especially for women and students from underprivileged socioeconomic backgrounds.