BII: Mechanisms of Cellular Evolution

通过整合生命科学、物理科学和数学科学中不同的领域，该研究所旨在产生对进化过程的机械理解。总体目标是破译进化在细胞水平上进行的一般规则，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。一个直接的目标是确定生命之树中细胞进化的各个方面是如何受到以下因素的支配的：细胞内部约束，生物物理学和生物能量学定律，以及种群的遗传特征。具体项目包括：细胞如何将其能量预算分配到一系列结构和功能的定量调查；理论的发展，以理解在不同的谱系中，进化改变的开放与封闭的路径；细胞中主要分子机器的结构和功能的比较分析并利用实验室微生物种群来确定细胞对温度和营养挑战的进化和发育反应。通过确定细胞水平上的关键细节，该研究所将极大地扩展我们对进化过程背后机制的理解，同时也揭示了具有新型有益功能的工程微生物和根除有害病原体的合理策略。一系列的活动，包括与合作者的学生交换计划，年度研讨会，教育材料的开发，以及建立一个蜂窝信息的地图集，将扩大研究所的范围到国家和国际层面。在此期间，该研究所有望与广泛的综合研究和教育重点联系起来，其共同目标是将进化生物学的新维度带入细胞生物学，反之亦然。研究从几个多方面的项目开始，第一个项目使用比较基因组学、空间细胞内蛋白质组学、超微显微镜和生物能量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。第二个项目从经验观察中吸取经验，为细胞生物学特征进化的机制建立定量理论，特别是进化利用的路径如何在系统上发生变化。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，以评估细胞大小和生长速度在营养、温度和种群遗传条件梯度上的选择所产生的基因组变化，并试图理解为什么生长速度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上的生命规则，并从基本原理为它们建立机制解释。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。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.