Stochastic Transport in Biology: From Molecules to Ecosystems

智力价值：运输现象与所有级别的生物组织和跨度、长度和时间尺度有关，涉及许多数量级。这一范围的一端是分子过程，例如离子通过细胞膜的运输，另一端是鸟类和动物跨越洲际距离的迁徙。这些现象的一个共同特征是其内在的随机性，以及它们发生的结构复杂和动态的环境。单细胞有机体在寻找有利条件时，依赖于随机的分子水平的受体结合事件来确定其在每个时刻的运动方向，这给其整体轨迹带来了随机性。因此，分子水平上的随机性产生了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交通行为。这样的观察表明，假设一个组织级别的随机过程可以以可预测的方式在较高组织级别的随机传输现象中表现出来。这个项目将开发一个基于扩散物理学的通用理论框架，以在生物组织的三个不同层面上研究这些想法。在分子水平上，这个项目将探索随机性如何影响分子马达运动蛋白的运输，以及拉动同一超分子货物的多个马达的集体运输行为。在细胞一级，该项目将描述细胞骨架网络上的马达驱动的货物运输，这些细胞骨架网络基本上被认为是静态的，或者更现实地说，正在改变与运输过程本身相当的时间尺度。最后，在多细胞水平上，该项目将开发模型来探索细胞通信和空间复杂性在蓝藻向光源移动的多细胞群落中运输驱动的图案形成中的作用。更广泛的影响：在组织的分子、细胞和多细胞层面上基本了解运输的基本物理学，将对生物学研究和生物技术，特别是对运输过程的最佳设计和控制具有广泛的意义。此外，这项研究的一般理论将对动态计算机网络上的信息传输和路由以及大规模、动态生态和人类网络上的种群传播等问题具有一定的指导意义。和平协会和共同和平协会还将在其机构内和在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个成功和创新的基于微积分的新生水平的物理序列，使用生物实例来激励和说明物理概念。这门课程将进一步发展，增加新的计算实验室和一个基于Flash动画的互动网站，允许学生在他们的计算机上探索物理概念和他们的生物联系。PI将与当地社区大学合作，培训教师如何使用这些新的课程材料，旨在为生命科学入门课程增加一个令人兴奋的定量重点。更多的外展活动针对的是当地的高中，并与联合PI一起，在湾区的高中，特别是针对妇女和具有贫困社会经济背景的学生。

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.