CAREER:Research and Education in Theoretical Biophysics: Physical Principles Governing Biochemical Signaling Networks

这个职业奖的研究目标旨在理解控制生化信号网络设计的原则。细胞的关键功能，生长、分化和特殊特性的产生，都是通过生化反应网络来完成的。该研究将检验基础物理学设定的理论限制，例如导致化学动力学速率波动的热波动和扩散噪声，以及生化信号的准确性。在物理定律设定的极限下，将探索性能的概念，以了解细胞的生化信号处理，从单个网络元件的水平，如生化开关，到早期胚胎发育中控制精确形态梯度检测的信号网络的组织。确保对固有噪声源的鲁棒性的设计原则将研究各种生化信号网络，如细菌趋化信号转导网络和光转导在脊椎动物视网膜细胞。生物化学信号处理的最优性将在信息理论考虑的良好特征的细菌信号转导网络的背景下进行探讨。在物理极限下的性能等组织原则将用于约束未知和部分已知的分子机制。属于该职业活动长期范围的协同活动包括与生物学家就直接受到实验启发的问题进行合作。这些包括了解新月茎杆菌营养摄取的最佳策略，以及生物膜形成初期运动性和趋化性的作用。教育部分建立在研究平台的跨学科性质上，为进一步发展印第安纳大学布卢明顿分校物理系新生的研究生生物物理学项目提供了种子计划，并将其与本科课程相结合。它包含了三个层次的课程开发，针对非科学家，本科科学专业以及高级研究生。教育和推广工作的强烈目标是这样一种观念，即科学家和非科学家都面临着需要多学科训练和思考的问题。该奖项的资金由数学和物理科学理事会的物理系以及生物科学理事会的分子和细胞生物科学系提供。

The research objective of this CAREER award aims at understanding the principles governing the design of biochemical signaling networks. The cell's crucial functions, growth, differentiation and the generation of specialized properties, are carried out by networks of biochemical reactions. The research will examine the theoretical limits set by fundamental physics, such as thermal fluctuations leading to chemical kinetic rate fluctuations and diffusive noise, on the accuracy of biochemical signaling. The idea of performance at the limits set by physical laws will be explored to understand biochemical signaling processing by the cell, from the level of a single network element, such as a biochemical switch, to the organization of the signaling network governing precise morphogen gradient detection in early embryonic development. Design principles ensuring robustness to inherent sources of noise will be investigated for various biochemical signaling networks, such as the bacterial chemotaxis signal transduction network and phototransduction in vertebrate retinal cells. Optimality in biochemical signal processing will be explored in the context of the well-characterized bacterial signal transduction network from information theoretic considerations. Organizing principles such as performance at physical limits will be used to constrain unknown and partially known molecular mechanisms. Synergistic activities that fall under the long-term scope of this CAREER activity involve ongoing collaborations with biologists on problems inspired directly by experiments. These include understanding optimal strategies in nutrient uptake by Caulobacter crescentus and the role of motility and chemotaxis in initial stages of biofilm formation. The educational component builds on the interdisciplinary nature of the research platform and provides seed initiatives for further developing the nascent graduate biophysics program in the Physics department at Indiana University, Bloomington, and interfacing it with the undergraduate curriculum. It encompasses the development of courses at three levels, for non-scientists, undergraduate science majors as well as advanced graduate students. The education and outreach efforts are strongly aimed at the notion that scientists and non-scientists alike are confronted by issues and problems that require multidisciplinary training and thinking.Funding for this award is provided by the Division of Physics in the Directorate for Mathematical and Physical Sciences and by the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences.