COBRE: UID: PROJ 3: MOLECULAR DISSECTION OF ADAPTIVE EVOLUTION

COBRE：UID：项目 3：自适应进化的分子解剖

• 批准号: 8359577
• 负责人: CELESTE J BROWN
• 金额: $ 23.74万
• 依托单位: UNIVERSITY OF IDAHO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8359577
• 关键词: Achievement; Address; Amino Acid Substitution; Bacteriophages; Biochemical; Biological Assay; Biological Models; Centers of Research Excellence; Dissection; Drug resistance; Environment; Evolution; Funding; Gene Expression; Gene Expression Regulation; Goals; Grant; Host resistance; Human; Lead; Longevity; Modeling; Molecular; National Center for Research Resources; Nucleic Acid Regulatory Sequences; Pathway interactions; Principal Investigator; Process; Proteins; Relative (related person); Research; Research Infrastructure; Resources; Source; Temperature; Testing; Time; United States National Institutes of Health; Virulence; base; cost; microbial; mutant; predictive modeling

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Microbial evolution occurs on a time scale that is rapid relative to the human lifespan and can lead to changes in virulence, host and drug resistance. The long term goal of this project is to determine whether there are general principles that can be used to predict the molecular basis of short term adaptive evolution. The focus of the proposal is to develop a deeper understanding of the mechanistic basis of adaptive evolution using icosahedral bacteriophage as a model system. The specific aims are 1) to determine the structural basis of protein adaptation using biochemical and biophysical principles; and 2) to determine the contribution of regulatory substitutions to adaptive evolution. To address the first aim, we will identify amino acid substitutions that increase or decrease temperature range in evolved phage and dissect the biophysical mechanisms underlying these adaptations. We will use this information to build a predictive model of thermal adaptation and test this model by predicting the relative temperature range of phages taken from the environment, and by constructing predicted thermal mutants in a related phage. To address the second aim, we will use gene expression and phenotypic assays to determine which experimentally observed changes in regulatory regions exert their adaptive effects by altering gene expression. We will also determine the magnitude of the changes and the context in which they are adaptive and identify selective conditions that promote changes in gene regulation. Successful achievement of these aims will enhance our ability to predict the probable pathways of adaptive evolution.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 微生物进化发生的时间尺度相对于人类寿命来说很快，并且可能导致毒力、宿主和耐药性的变化。该项目的长期目标是确定是否存在可用于预测短期适应性进化的分子基础的一般原理。该提案的重点是使用二十面体噬菌体作为模型系统，更深入地了解适应性进化的机制基础。具体目标是1）利用生物化学和生物物理原理确定蛋白质适应的结构基础； 2）确定监管替代对适应性进化的贡献。为了实现第一个目标，我们将确定在进化的噬菌体中增加或减少温度范围的氨基酸取代，并剖析这些适应背后的生物物理机制。我们将利用这些信息建立热适应的预测模型，并通过预测从环境中获取的噬菌体的相对温度范围以及在相关噬菌体中构建预测的热突变体来测试该模型。为了实现第二个目标，我们将使用基因表达和表型测定来确定哪些实验观察到的调节区域的变化通过改变基因表达来发挥其适应性作用。我们还将确定变化的幅度以及它们适应的背景，并确定促进基因调控变化的选择性条件。成功实现这些目标将增强我们预测适应性进化的可能途径的能力。