BII: Mechanisms of Cellular Evolution

通过整合生命、物理和数学科学中的不同领域，该研究所旨在产生对进化过程的机械性理解。其广泛的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，以帮助建立一个正式的进化细胞生物学领域。一个直接的目标是确定生命树上细胞进化的各个方面是如何管理的：内部细胞限制，生物物理学和生物能量学的定律，以及种群的遗传特征。具体项目包括：对细胞如何将其能量收支分配到一系列结构和功能进行量化调查；开发理论以了解不同谱系的进化修饰是开放的还是封闭的；对细胞中主要分子机器的结构和功能能力进行比较分析；以及利用实验室微生物实验种群来确定细胞在进化和发育过程中如何对温度和营养挑战做出反应。通过在细胞水平上确定关键细节，该研究所将极大地扩展我们对进化过程潜在机制的理解，同时还揭示了设计具有新的有益功能的微生物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、年度讲习班、编写教材和建立蜂窝信息地图集，将把研究所的覆盖范围扩大到国家和国际两级。在整个过程中，该研究所预计将与广泛的综合研究和教育重点相联系，共同目标是将进化生物学的新维度引入细胞生物学，反之亦然。这项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、细胞内空间蛋白质组学、超微结构和生物能量学分析来提供对细胞特征以及建造和操作它们的相对成本的广泛的系统学概述。第二个项目从经验观察出发，为细胞生物学特征的进化机制建立量化理论，特别是进化利用的途径如何在系统发生上发生变化。该项目还采用了结构生物学的方法来探索具有基本和高度保守功能的主要细胞复合体，如ATP合成酶和核糖体，如何在进化上自由分化。第三个项目在已建立的微生物长期进化实验的基础上进行资本化和扩展，以评估在营养、温度和种群遗传条件的梯度上对细胞大小和生长速度进行选择而产生的基因组变化，并试图了解为什么生长速度和细胞大小的系统发育标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层面的生命规则，并从基本原理出发为它们建立机械解释。合作项目涉及来自不同背景的科学家，从地方到国家/国际层面向外建立。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.