Systems Biology of Protein and Phenotypic Evolution

蛋白质和表型进化的系统生物学

基本信息

批准号：
10611895
负责人：
Dennis Vitkup
金额：
$ 43.94万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2025-04-30
项目状态：
未结题

项目摘要

Project Summary/Abstract An important and currently unsolved challenge in evolutionary systems biology is to describe how the mechanisms and interactions between different levels of biological organization shape the evolution of proteins, cellular networks, and phenotypes. Our laboratory has been interested in understanding the inter-relationships between evolution and systems and cell biology for more than a decade. We have previously carried out computational and experimental analyses exploring evolutionary processes at multiple levels of organization. In this proposal we will integrate constraints and effects at the protein, network, cellular, and phenotypic scales, towards developing an integrated and quantitative framework describing protein evolution. We will use a combined computational-experimental approach to pursue such fundamental scientific questions as: How do global protein fitness landscapes affect short- and long-term patterns of protein evolution? How do the structure and function of cellular networks affect protein evolutionary changes? What is the role of cell type- and tissue-specific constraints on protein evolution? How does the evolution of protein repertoires influence the observed patterns and rates of phenotypic evolution? Because biological systems not only constrain, but are also themselves the products of evolution, exploring the aforementioned topics will also allow us to address important biological questions. For example, how and to what extent protein expression levels and the efficiency of protein function are optimized in evolution, and how changes in cellular networks may drive microbial phenotypic evolution. In addition to understanding fundamental biological questions, proposal results will have important implications for biomedicine. Specifically, they will allow to better understand and predict the quantitative effects of genetic mutations on protein function, cellular networks, diverse cell types and developmental stages, and ultimately on species’ phenotypes.

项目摘要/摘要进化系统生物学中的一个重要且目前尚未解决的挑战是描述不同级别的生物组织之间的机制和相互作用塑造蛋白质，细胞网络和表型的演变。我们的实验室已经有兴趣了解进化与系统与细胞生物学之间的关系十多年来。我们以前已经进行了计算和实验分析探索多个组织级别的进化过程。在这个建议中，我们将在蛋白质，网络，细胞和表型尺度上的综合约束和效果朝向开发一个描述蛋白质进化的综合定量框架。我们将使用一个合并的计算实验方法来追求此类基本科学问题 AS：全球蛋白质健身景观如何影响蛋白质的短期和长期模式进化？细胞网络的结构和功能如何影响蛋白质进化变化？细胞类型和特异性约束在蛋白质进化中的作用是什么？如何蛋白质库的演化是否影响观察到的表型的模式和速率进化？因为生物系统不仅限制了，而且本身就是产品进化，探索理由的主题也将使我们能够解决重要的生物学问题。例如，如何以及如何在何种程度上蛋白质表达水平和效率蛋白质功能在进化中优化，细胞网络的变化如何驱动微生物表型进化。除了了解基本的生物学问题外，提案结果将对生物医学有重要影响。具体来说，他们将允许更好地理解和预测遗传突变对蛋白质功能的定量影响，蜂窝网络，潜水细胞类型和发育阶段，最终在物种上表型。