Predictive biophysical models of evolution

进化的预测生物物理模型

基本信息

  • 批准号:
    9234799
  • 负责人:
  • 金额:
    $ 56.94万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2004
  • 资助国家:
    美国
  • 起止时间:
    2004-04-01 至 2020-11-30
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract The overarching goal of the proposed research is to develop predictive multiscale biophysical models of adaptive evolutionary dynamics. In earlier work we demonstrated for several cases of biomedical importance that fitness effect of genetic variation can be accurately predicted from a unique combination of molecular traits of the mutated protein. This finding transforms the concept of fitness landscape from an artful metaphor into a quantitative tractable tool to predict the genotype-phenotype relationship (GPR). Here we take these findings as a foundation to further extend our understanding of interplay between biophysical and population factors that determine the dynamics and outcome of adaptive evolution. We will apply microfluidics and automatic robotics setup along with protein engineering and genomic editing tools to explore evolutionary dynamics in laboratory experiments under conditions that allow tight control on all scales – from molecules to populations. To that end, we carry out a set of evolution experiments with adapting populations of E. coli escaping from antibiotic stress and structural instability of the essential protein Dihydrofolate Reductase. We characterize on all scales – genotyping, molecular traits, systems proteomics and population - multiple evolutionary paths to resistance and adaption of emerging bacterial strains and determine at which level of description (genotype, biophysical properties, systems responses) evolution becomes reproducible – and by implication predictable. In parallel we model the evolutionary dynamics using multiscale models where cytoplasm of model cells is presented in a biophysically realistic manner, and fitness of model organisms is predicted from its molecular traits using experimentally derived GPR. Molecular traits of mutant forms are predicted using state of the art computational tools of molecular biophysics allowing reproducing and predicting complete evolutionary trajectories of adapting populations of model cells. A tight integration between theory and experiment will provide an opportunity to develop predictive evolutionary models of ever increasing accuracy and realism. Progress along these lines will transform our approaches to study evolutionary dynamics from descriptive into predictive and quantitative, which will be instrumental to the development of novel approaches to fight antibiotic resistance and, potentially, viral escape from stressors such as drugs and immune response.
项目总结/文摘

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

EUGENE I SHAKHNOVICH其他文献

EUGENE I SHAKHNOVICH的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('EUGENE I SHAKHNOVICH', 18)}}的其他基金

Biophysical foundations of evolutionary dynamics
进化动力学的生物物理学基础
  • 批准号:
    10633124
  • 财政年份:
    2021
  • 资助金额:
    $ 56.94万
  • 项目类别:
Biophysical foundations of evolutionary dynamics
进化动力学的生物物理学基础
  • 批准号:
    10452241
  • 财政年份:
    2021
  • 资助金额:
    $ 56.94万
  • 项目类别:
Biophysical foundations of evolutionary dynamics
进化动力学的生物物理基础
  • 批准号:
    10413808
  • 财政年份:
    2021
  • 资助金额:
    $ 56.94万
  • 项目类别:
Structure and Interactions of Conformational Intermediates in gamma-D Crystallin Aggregation, and Their Targeting for Cataract Prevention
γ-D 晶状体蛋白聚集中构象中间体的结构和相互作用及其预防白内障的靶向作用
  • 批准号:
    10401812
  • 财政年份:
    2020
  • 资助金额:
    $ 56.94万
  • 项目类别:
Structure and Interactions of Conformational Intermediates in gamma-D Crystallin Aggregation, and Their Targeting for Cataract Prevention
γ-D 晶状体蛋白聚集中构象中间体的结构和相互作用及其预防白内障的靶向作用
  • 批准号:
    10608130
  • 财政年份:
    2020
  • 资助金额:
    $ 56.94万
  • 项目类别:
Study of phenotypic and fitness effects of non-functional protein interactions in
非功能性蛋白质相互作用的表型和适应度效应研究
  • 批准号:
    8912519
  • 财政年份:
    2014
  • 资助金额:
    $ 56.94万
  • 项目类别:
Study of Biological Evolution of Structure and Function in Proteins
蛋白质结构和功能的生物进化研究
  • 批准号:
    8624697
  • 财政年份:
    2004
  • 资助金额:
    $ 56.94万
  • 项目类别:
Evolutionary study of structure-function relationship
结构-功能关系的进化研究
  • 批准号:
    6773025
  • 财政年份:
    2004
  • 资助金额:
    $ 56.94万
  • 项目类别:
Realistic protein folding with hydrophobic potentials
具有疏水潜力的真实蛋白质折叠
  • 批准号:
    6844886
  • 财政年份:
    2004
  • 资助金额:
    $ 56.94万
  • 项目类别:
Evolutionary study of structure-function relationship
结构-功能关系的进化研究
  • 批准号:
    6874497
  • 财政年份:
    2004
  • 资助金额:
    $ 56.94万
  • 项目类别:

相似海外基金

The effects of antibiotics to the transfer frequency of the antibiotic resistance genes and the evolution of high-level resistance.
抗生素对抗生素抗性基因转移频率和高水平抗性进化的影响。
  • 批准号:
    22K05790
  • 财政年份:
    2022
  • 资助金额:
    $ 56.94万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
NEC05839 Chicken or the Egg: Is AMR in the Environment Driven by Dissemination of Antibiotics or Antibiotic Resistance Genes?
NEC05839 先有鸡还是先有蛋:环境中的抗菌素耐药性是由抗生素或抗生素抗性基因的传播驱动的吗?
  • 批准号:
    NE/N019687/2
  • 财政年份:
    2019
  • 资助金额:
    $ 56.94万
  • 项目类别:
    Research Grant
Combating Antibiotic Resistance to Aminoglycoside Antibiotics through Chemical Synthesis
通过化学合成对抗氨基糖苷类抗生素的耐药性
  • 批准号:
    392481159
  • 财政年份:
    2017
  • 资助金额:
    $ 56.94万
  • 项目类别:
    Research Fellowships
NEC05839 Chicken or the Egg: Is AMR in the Environment Driven by Dissemination of Antibiotics or Antibiotic Resistance Genes?
NEC05839 先有鸡还是先有蛋:环境中的抗菌素耐药性是由抗生素或抗生素抗性基因的传播驱动的吗?
  • 批准号:
    NE/N019687/1
  • 财政年份:
    2016
  • 资助金额:
    $ 56.94万
  • 项目类别:
    Research Grant
Chicken or the Egg: Is AMR in the Environment Driven by Dissemination of Antibiotics or Antibiotic Resistance Genes?
先有鸡还是先有蛋:环境中的抗菌素耐药性是由抗生素或抗生素抗性基因的传播驱动的吗?
  • 批准号:
    NE/N019857/1
  • 财政年份:
    2016
  • 资助金额:
    $ 56.94万
  • 项目类别:
    Research Grant
The SuDDICU study- A study of the impact of preventative antibiotics (SDD) on patient outcome and antibiotic resistance in the critically ill in intensive care
SuDDICU 研究 - 一项关于预防性抗生素 (SDD) 对重症监护病危患者的患者预后和抗生素耐药性影响的研究
  • 批准号:
    366555
  • 财政年份:
    2016
  • 资助金额:
    $ 56.94万
  • 项目类别:
    Operating Grants
Chicken or the Egg: Is AMR in the Environment Driven by Dissemination of Antibiotics or Antibiotic Resistance Genes?
先有鸡还是先有蛋:环境中的抗菌素耐药性是由抗生素或抗生素抗性基因的传播驱动的吗?
  • 批准号:
    NE/N019717/1
  • 财政年份:
    2016
  • 资助金额:
    $ 56.94万
  • 项目类别:
    Research Grant
The SuDDICU study- A study of the impact of preventative antibiotics (SDD) on patient outcome and antibiotic resistance in the critically ill in intensive care
SuDDICU 研究 - 一项关于预防性抗生素 (SDD) 对重症监护病危患者的患者预后和抗生素耐药性影响的研究
  • 批准号:
    361307
  • 财政年份:
    2016
  • 资助金额:
    $ 56.94万
  • 项目类别:
    Operating Grants
RAPID: COLLABORATIVE RESEARCH: Fate and Transport of Antibiotics and Antibiotic Resistance Genes During Historic Colorado Flood
快速:合作研究:历史性科罗拉多洪水期间抗生素和抗生素抗性基因的命运和运输
  • 批准号:
    1402635
  • 财政年份:
    2013
  • 资助金额:
    $ 56.94万
  • 项目类别:
    Standard Grant
Contamination status of antibiotics and antibiotic resistance genes (ARGs) in tropical Asian aquatic environments with artificial and natural disturbance
人工和自然干扰下亚洲热带水生环境中抗生素和抗生素抗性基因(ARG)的污染状况
  • 批准号:
    25257402
  • 财政年份:
    2013
  • 资助金额:
    $ 56.94万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了