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

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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.