Theoretical Principles of Genotype-Phenotype Mapping

这项工作的目的是为理解基因（基因型）和性状（表型）之间的联系建立一个理论框架。基因型和表型之间的联系是复杂的，目前还没有足够的理论将基因型和表型联系起来。这种理论的发展对于理解有机体的发展和进化都是至关重要的。这是因为发育是基于基因型中包含的信息而形成表型的过程，也因为进化是通过选择表型而起作用的，然后导致基因型的可遗传变化。本研究将利用一组不同复杂程度的分子、发育和代谢网络，其结构和动力学被很好地理解，以建立一个理论框架，将分子和细胞机制映射到表型性状。完整而明确地绘制基因与性状之间的关系是一项具有挑战性的任务，因为导致表型的分子和细胞机制是多样的、异质的，而且异常复杂。以前的理论工作使用了简化，不能解释整个过程的多样性。因此，理解表型是如何从本质上异构、非线性和非稳态的系统中产生的，需要在本研究中开发新的理论方法。该项目将为本科生和研究生提供一个跨学科的教育项目，包括物理化学、生物物理学、细胞生物学和计算生物学。

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.