Towards Understanding Fine-Scale Microbial Diversity

理解精细微生物多样性

• 批准号: 2210386
• 负责人: Daniel Fisher
• 金额: $ 94.36万
• 依托单位: Stanford University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2210386&HistoricalAwards=false
• 关键词: Towards; Understanding; Fine; Scale; Microbial

A major discovery of the DNA sequencing revolution is the huge number of bacterial species. Remarkably, this bacterial biodiversity extends far below species level down to the finest scales of genetic differences. For common human gut bacteria, people on opposite sides of the Earth may have very closely related strains, while people in the same household may have very different strains, and individuals can have multiple strains that are continually competing and evolving. For Prochlorococcus, a tiny, enormously abundant bacterium that dominates photosynthesis in the tropical oceans and fixes more carbon than all croplands combined, a bucketful of seawater includes a multitude of strains, some closely related, some very distant. The traditional explanation for the diversity of species is that each has its own ecological niche, or live in different locations so they do not compete. But for relatively simple bacteria that are mixed together by human motion and their interactions or by ocean currents, it is implausible that each strain has its own ecological niche. Why doesn't survival of the fittest drive almost all the strains extinct? The goal of the Project is to begin to unravel this puzzle. This Project will bring a spectrum of approaches to bear. A major part will be developing and exploring potential scenarios for creating and sustaining extensive diversity within microbial species. To understand whether and how scenarios might work, simple models that caricature the most important features will be studied theoretically. The simplicity of models is essential. The alternate approach of making as-realistic-as-possible models and simulating them on computers is highly problematic: how could one learn which features and predictions might apply to other species? But simple models do not mean they are simple to understand: the Project will involve developing new theoretical methods combining approaches from ecology, evolution, and statistical physics. One of the scenarios that will be explored arises from the perpetual battle between bacteria and phages -- viruses that attack bacteria. If a phage strain effectively attacks an abundant bacterial strain, it can kill off much of that strain, leaving room for other strains to bloom, which then stimulate other phage strains to evolve to attack them, as well as enabling mutant bacteria that resist the most abundant phages to arise and prosper. This "Red Queen" dynamics -- everyone running hard just to stay in place -- can cause an ecological and evolutionary chaotic state that could potentially drive and sustain extensive diversity. A key part of this Project is, from each scenario explored, to glean predictions that might obtain in Nature and find ways of testing these, especially by extensive DNA sequencing. In parallel with the theoretical developments, the Project will involve collaborations with microbial ecologists and experimenters to explore several bacterial species in depth via DNA sequencing from large numbers of single cells and from large populations of similar bacteria (and phages) extracted from natural environments or humans. To combine data of multiple types, and to extract the most significant understanding, will involve finding new statistical quantities and methods to measure them, together with mathematical analyses of the processes that might produce them. One of the important questions is to what extent the evolution of bacteria -- long thought to be primarily asexual -- is shaped or even dominated by exchange of DNA between them. Understanding the diversity and evolution within bacterial species that live on or in humans, or play crucial roles in the environment, is important for human health and for understanding how climate change will affect the fundamental processes that shape the oceans and atmosphere. And scientifically, diversity within a species is the root from which higher level diversity develops: advancing understanding of it will advance understanding of evolution and bio-diversity more broadly. This Project will bring together students and postdocs from a spectrum of backgrounds, including, academically, physics, biology, and computer science or statistics. Training them in all the needed disciplines is important for the Project's success and for the broader development of science and scientists.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.

DNA测序革命的主要发现是大量细菌物种。 值得注意的是，这种细菌生物多样性远远低于物种水平，直至遗传差异的最大程度。 对于人类常见的肠道细菌而言，地球对面的人们可能具有密切相关的菌株，而同一家庭中的人们可能会有非常不同的菌株，并且个人可以具有不断竞争和不断发展的多种菌株。对于占地氯环球菌，一种微小的，丰富的细菌在热带海洋中占主导地位，并固定了比所有合并的农田更多的碳，因此一桶海水包括许多菌株，有些密切相关，有些非常遥远，有些非常遥远。对物种多样性的传统解释是，每个物种都有自己的生态位，或生活在不同的地方，因此它们不竞争。但是，对于通过人类运动及其相互作用或洋流混合在一起的相对简单的细菌，每个菌株都有自己的生态位，这是令人难以置信的。 为什么最适合驱动的生存几乎所有菌株都不灭绝？该项目的目的是开始解开这个难题。 该项目将带来各种各样的方法。一个主要的部分是开发和探索在微生物物种中创造和维持广泛多样性的潜在情景。要了解场景是否可能工作，将在理论上研究最重要的功能的简单模型。模型的简单性至关重要。制作现实主义模型并在计算机上模拟它们的替代方法是高度问题：一个人如何学习哪些特征和预测可能适用于其他物种？ 但是简单的模型并不意味着它们简单地理解：该项目将涉及开发新的理论方法，结合了生态学，进化和统计物理学的方法。 将要探索的场景之一是源于细菌和噬菌体之间的永久战斗 - 攻击细菌的病毒。 如果噬菌体菌株有效地攻击了丰富的细菌菌株，它可能会杀死大部分菌株，留出其他菌株的空间，然后刺激其他噬菌体菌株进化以攻击它们，并启用可抵抗最大的突变细菌大量的噬菌体出现和繁荣。 这种“红皇后”的动力 - 每个人都努力呆在原地 - 可能会导致一种生态和进化的混乱状态，该状态可能会推动和维持广泛的多样性。 该项目的关键部分是从探索的每种情况下，都可以收集可能在本质上获得的预测，并找到测试这些预测，尤其是通过广泛的DNA测序。 与理论发展同时，该项目将涉及与微生物生态学家和实验者的合作，以通过大量单细胞和大量类似细菌（和噬菌体）从自然环境或人类或人类提取的大量种群中进行DNA测序深入探索几种细菌物种。 。为了结合多种类型的数据并提取最重要的理解，将涉及寻找新的统计数量和方法来测量它们，以及可能产生它们的过程的数学分析。重要的问题之一是细菌的演变在多大程度上 - 长期以来被认为是无性无性的 - 由它们之间的DNA交换来塑造甚至主导。 了解生活在人类或人类中或在环境中起关键作用的细菌物种中的多样性和进化对于人类健康至关重要，对于了解气候变化将如何影响塑造海洋和气氛的基本过程。从科学上讲，一个物种内的多样性是更高层次多样性发展的根源：促进对其的理解将更广泛地提高人们对进化和生物多样性的理解。 该项目将汇集来自各种背景的学生和博士后，包括学术，物理学，生物学以及计算机科学或统计学。 在所有必要的学科中培训他们对于项目的成功和更广泛的科学和科学家的发展至关重要。该奖项反映了NSF的法定任务，并且被认为是值得通过基金会的知识分子优点和更广泛的影响评估的评估来支持的。