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：
10385809
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 2024-04-30
项目状态：
已结题

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.

项目概要/摘要进化系统生物学中一个重要且目前尚未解决的挑战是描述生物组织不同层次之间的机制和相互作用我们的实验室一直致力于塑造蛋白质、细胞网络和表型的进化。有兴趣了解进化与系统和细胞生物学之间的相互关系十多年来，我们已经进行了计算和实验分析。在本提案中，我们将探索组织多个层面的演化过程。整合蛋白质、网络、细胞和表型尺度的限制和影响，我们将使用一个描述蛋白质进化的综合定量框架。结合计算实验的方法来解决这些基本的科学问题如下：全球蛋白质适应性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？细胞类型和组织特异性限制对蛋白质进化的作用是什么？蛋白质库的进化是否影响观察到的表型模式和速率因为生物系统不仅是进化的产物，而且本身也是进化的产物。关于进化论，探索所讨论的主题也将使我们能够解决重要的生物学问题例如，蛋白质表达水平如何以及程度如何以及效率。蛋白质功能在进化中得到优化，以及细胞网络的变化如何驱动除了了解基本的生物学问题之外，微生物表型进化。提案结果将对生物医学产生重要影响。更好地理解和预测基因突变对蛋白质功能的定量影响，细胞网络、不同的细胞类型和发育阶段，并最终影响物种的表型。