Developing a Landscape Theory for Biological Networks: Principle Concepts and Physical Perspectives

该项目的目标是了解生物网络的功能、健壮性和进化的基本机制。PI将通过几个综合步骤研究生物网络。首先，他将发展一个潜在景观的普遍概念，并在此基础上建立一个理论框架，以全局和物理方式理解生物网络的稳健性，进化和功能。其次，PI将开发有效的计算方法来研究大型现实生物网络的底层景观的功能和特性。通过这种方式，PI将能够在统计上处理大自由度，并超越对巨大状态空间进行搜索的任何计算瓶颈。第三，PI将通过景观框架探索在发育过程中细胞命运决定的特定生物网络和捕食-猎物合成生态系统的动态，揭示结构-功能关系。PI将探索细胞分化方向性的起源。该项目还将探索如何对单细胞细菌进行编程，使其表现出复杂的行为，以及如何以调节基因表达的信号分子的形式，很好地控制信息交换，在相互作用的种群动态中表现出来。该项目的主要智力价值在于通过发展跨不同生物组织水平的景观的通用概念和理论框架，了解全球物理原理、功能和生命系统的稳健性。该项目通过教育、培训和外联活动产生更广泛的影响。PI将通过设计跨学科课程和生物网络系列研讨会来教育不同背景的学生，将他的研究与他的教育工作结合起来。他将在生物网络领域开展国内外合作、联合研究和合作教育活动。PI将指导博士后研究人员，并帮助他为进一步的学术或工业职业发展做准备。这个项目也会让一些当地的高中生参与暑期研究项目，进行外展教育。PI计划向公众撰写通俗的文章，以图片的方式介绍景观概念，使人们容易掌握基本概念。

The objective of this project is to understand fundamental mechanisms of function, robustness, and evolution of biological networks. The PI will study biological networks in several integrated steps. First, he will develop a universal concept of potential landscapes and establish a theoretical framework based on it to understand robustness, evolution, and function of biological networks in a global and physical way. Second, the PI will develop efficient computational methods to study functions and properties of the underlying landscape for large realistic biological networks. In this way, the PI will be able to deal with large degrees of freedom statistically and surpass any computational bottleneck of search for the vast state space. Third, the PI will explore specific biological networks of cell fate decision in the developmental process and the dynamics of a predator-prey synthetic ecosystem, through the landscape framework, to uncover structure-function relationships. The PI will explore the origin of directionality of cell differentiation. The PI will also explore how the single celled bacteria can be programmed to exhibit complex behavior, and how well controlled exchanges of information, in the form of signaling molecules that regulate gene expression, manifest themselves in the dynamics of interacting populations. The major intellectual merit of this project lies in the understanding of global physical principles, function and robustness of living systems through the development of a universal concept and theoretical framework of landscape across different levels of biological organization.The broader impact associated with the project is through education, training and outreach activities. The PI will integrate his research with his education efforts by designing an interdisciplinary course and a seminar series on biological networks to educate students from different backgrounds. He will initiate domestic and international collaborative joint research and co-education activities on biological networks. The PI will mentor a post doctoral researcher and help him to prepare for further academic or industrial career advancement. This project will also involve some local high school students for summer research projects for outreach education. The PI plans to write popular articles to the public to introduce the landscape concept in a pictorial way so that people can easily grasp the basic ideas.