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

该职业奖的研究目标旨在了解生物化学信号网络设计的原则。细胞的关键功能，生长，分化和特殊性质的产生，是通过生化反应网络进行的。该研究将研究基础物理学设定的理论极限，例如导致化学动力学速率波动和扩散噪声的热波动，以及生物化学信号的准确性。物理定律所设定的极限性能的想法将被探索，以了解生化信号处理的细胞，从一个单一的网络元素，如生化开关的水平，组织的信号网络管理精确的形态梯度检测在早期胚胎发育。设计原则，确保鲁棒性的固有噪声源将调查各种生化信号网络，如细菌趋化性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充分表征的细菌信号转导网络的背景下，从信息论的考虑进行探索。组织原则，如在物理极限的性能将被用来约束未知和部分已知的分子机制。属于本CAREER活动长期范围的协同活动涉及与生物学家就直接受实验启发的问题进行的持续合作。这些包括了解新月柄杆菌营养吸收的最佳策略以及生物膜形成初始阶段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，并提供种子倡议，进一步发展新生的研究生生物物理学计划在印第安纳州大学物理系，布卢明顿，并与本科课程接口。它包括三个层次的课程开发，为非科学家，本科科学专业以及高级研究生。教育和宣传工作的主要目标是，科学家和非科学家都面临需要多学科培训和思考的问题，该奖项由数学和物理科学局物理处和生物科学局分子和细胞生物科学处提供资金。

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.