Theoretical Principles of Genotype-Phenotype Mapping

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The aim of this work is to develop a theoretical framework for understanding the linkage between genes (the genotype) and traits (the phenotype). The linkage between genotype and phenotype is complex, and there is at present no adequate theory that links genotype to phenotype. Development of such a theory is critical for understanding both organismal development and evolution. This is because development is the process by which phenotypes are made based on information contained in the genotype, and because evolution acts by selecting phenotypes, which then results in heritable changes in the genotype. This research will make use of a set of molecular, developmental and metabolic networks of different degrees of complexity, whose structure and kinetics are well-understood, to develop a theoretical framework to map molecular and cellular mechanism to phenotypic traits. Complete and explicit mapping of how genes are connected to traits is a challenging task because the molecular and cellular mechanisms that give rise to the phenotype are diverse, heterogeneous, and exceptionally complex. Previous theoretical work has used simplifications that do not account for the entire diversity of processes. Understanding how phenotypes emerge from systems that are inherently heterogeneous, non-linear and non-steady state therefore requires novel theoretical approaches that will be developed in this research. The project will contribute to an interdisciplinary education program that integrates physical chemistry, biophysics, cellular biology and computational biology for undergraduate and graduate students.