BII: Mechanisms of Cellular Evolution

BII：细胞进化机制

• 批准号: 2119963
• 负责人: Michael Lynch
• 金额: $ 1250万
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Cooperative Agreement
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2119963&HistoricalAwards=false
• 关键词: BII; Mechanisms; Cellular; Evolution

By integrating across disparate fields in the life, physical, and mathematical sciences, this institute is designed to yield a mechanistic understanding of evolutionary processes. The broad goal is to decipher the general rules by which evolution proceeds at the cellular level, while simultaneously engaging in research and educational activities to help build a formal field of evolutionary cell biology. An immediate goal is to determine how aspects of cellular evolution across the Tree of Life are governed by: internal cellular constraints, the laws of biophysics and bioenergetics, and the genetic features of populations. Specific projects include: a quantitative survey of how cells apportion their energy budgets into a range of structures and functions; the development of theory to understand the paths that are open vs. closed to evolutionary modification in various lineages; comparative analyses of the structures and functional capacities of the major molecular machines in cells; and the use experimental laboratory populations of microbes to determine how cells respond evolutionarily and developmentally to temperature and nutritional challenges. By identifying key details at the cellular level, the institute will greatly expand our understanding of mechanisms underlying evolutionary processes, while also revealing rational strategies for engineering microbes with novel beneficial functions and for eradicating harmful pathogens. A range of activities, including student-exchange programs with collaborators, annual workshops, development of educational materials, and establishment of an atlas of cellular information will expand the reach of the institute to national and international levels. Over its duration, the institute is expected to connect with a wide range of integrative research and educational foci, with a common goal of bringing a new dimension of evolutionary biology to cell biology and vice versa. The research starts with several multifaceted projects, the first using comparative genomics, spatial intracellular proteomics, ultramicroscopy, and bioenergetic analyses to provide a broad phylogenetic overview of cellular features and the relative costs of constructing and operating them. The second project draws from empirical observations to build quantitative theory for the mechanisms by which cell-biological features evolve, in particular how the paths open to evolutionary exploitation vary phylogenetically. This project also takes a structural-biology approach to explore how major cellular complexes with essential and highly conserved functions, e.g., ATP synthase and ribosomes, are nonetheless free to diverge evolutionarily. The third project capitalizes and expands upon established long-term evolution experiments with microbes to evaluate the genomic changes that arise in response to selection on cell size and growth rate over gradients of nutrient, temperature, and population-genetic conditions, and seeks to understand why the phylogenetic scalings of growth rates and cell sizes have opposite directionality in prokaryotes and eukaryotes. The integration of these projects will reveal the Rules of Life at the cellular level and establish mechanistic explanations for them from first principles. Involving work from scientists from diverse backgrounds, the collaborative projects build outwardly from the local to the national/international level.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

通过整合生命、物理和数学科学的不同领域，该研究所旨在产生对进化过程的机械理解。其总体目标是破译细胞水平上进化的一般规则，同时参与研究和教育活动，以帮助建立进化细胞生物学的正式领域。当前的目标是确定生命之树的细胞进化的各个方面是如何受以下因素支配的：内部细胞限制、生物物理学和生物能量学定律以及群体的遗传特征。具体项目包括：对细胞如何将其能量预算分配到一系列结构和功能中的定量调查；理论的发展以理解不同谱系中进化修改的开放路径和封闭路径；细胞中主要分子机器的结构和功能的比较分析；以及使用实验实验室微生物群体来确定细胞如何在进化和发育上对温度和营养挑战作出反应。通过识别细胞水平的关键细节，该研究所将极大地扩展我们对进化过程背后机制的理解，同时也揭示了工程微生物具有新的有益功能和根除有害病原体的合理策略。一系列活动，包括与合作者的学生交流计划、年度研讨会、教材开发以及细胞信息图谱的建立，将把该研究所的影响范围扩大到国家和国际层面。在其成立期间，该研究所预计将与广泛的综合研究和教育焦点建立联系，其共同目标是将进化生物学引入细胞生物学的新维度，反之亦然。该研究从几个多方面的项目开始，第一个使用比较基因组学、空间细胞内蛋白质组学、超显微镜和生物能分析来提供细胞特征的广泛系统发育概述以及构建和操作它们的相对成本。第二个项目根据经验观察建立细胞生物学特征进化机制的定量理论，特别是进化利用的路径如何在系统发育上变化。该项目还采用结构生物学方法来探索具有基本和高度保守功能的主要细胞复合物（例如 ATP 合酶和核糖体）如何在进化上自由分化。第三个项目利用并扩展了已建立的微生物长期进化实验，以评估在营养、温度和群体遗传条件梯度上对细胞大小和生长速率的选择所产生的基因组变化，并试图理解为什么生长速率和细胞大小的系统发育尺度在原核生物和真核生物中具有相反的方向性。这些项目的整合将揭示细胞水平的生命规则，并从第一原理为它们建立机械解释。这些合作项目涉及来自不同背景的科学家的工作，从地方到国家/国际层面向外发展。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

EukProt: a database of genome-scale predicted proteins across the diversity of eukaryotes

• DOI: 10.1101/2020.06.30.180687
• 发表时间: 2020-07
• 期刊: bioRxiv
• 作者: D. Richter;C. Berney;Jürgen F. H. Strassert;Y. Poh;Emily K. Herman;Sergio A. Muñoz-Gómez;Jeremy G. Wideman;Fabien Burki;C. de Vargas

Revisiting the notion of deleterious sweeps.

重新审视有害扫描的概念。

• DOI: 10.1093/genetics/iyab094
• 发表时间: 2021
• 期刊: Genetics
• 影响因子: 3.3
• 作者: Johri,Parul;Charlesworth,Brian;Howell,EmmaK;Lynch,Michael;Jensen,JeffreyD
• 通讯作者: Jensen,JeffreyD

The fidelity of transcription in human cells.

• DOI: 10.1073/pnas.2210038120
• 发表时间: 2023-01-31
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Chung, Claire;Verheijen, Bert M.;Zhang, Xinmin;Huang, Biao;Coakley, Aeowynn;McGann, Eric;Wade, Emily;Dinep-Schneider, Olivia;LaGosh, Jessica;Anagnostou, Maria-Eleni;Simpson, Stephen;Thomas, Kelly;Ernst, Mimi;Rattray, Allison;Lynch, Michael;Kashlev, Mikhail;Benayoun, Berenice A.;Li, Zhongwei;Strathern, Jeffrey;Gout, Jean-Francois;Vermulst, Marc
• 通讯作者: Vermulst, Marc

Challenges and potential solutions for studying the genetic and phenotypic architecture of adaptation in microbes

• DOI: 10.1016/j.gde.2022.101951
• 发表时间: 2022-07-04
• 期刊: CURRENT OPINION IN GENETICS & DEVELOPMENT
• 影响因子: 4
• 作者: Brettner, Leandra;Ho, Wei-Chin;Geiler-Samerotte, Kerry
• 通讯作者: Geiler-Samerotte, Kerry