MIM: A thermodynamic theory of microbiome assembly, adaptation and evolution evaluated using modular microbial environments

在地球的生态系统中，微生物适应并形成跨越能量和资源丰富度梯度的群落（微生物组）。就像我们设计的机器和电路一样，功率和效率是决定微生物在群落中竞争力的关键特征。在进化过程中，微生物已经优化了自己的分子机器，以高效率转换可用能量，最大限度地减少了热量等废弃能量的损失。微生物有一系列的策略，反映了新细胞生产率（功率）与其效率（产量）之间的平衡，同时也处理各种降低产量的生存成本。该研究项目将测试微生物组的假设，即微生物组由个体成员组成，形成社区，在提高效率的同时优化功率。这种功率和效率优化的原理可以普遍应用于从蛋白质到生态系统的不同生物组织水平。研究人员将研究来自土壤和人类肠道的微生物组作为模型系统来测试这一想法。他们将开发一个新的实验平台，涉及多个隔室来控制微生物组如何相互作用，集成纳米技术传感器来测量微生物效率作为热量输出，加上先进的显微镜来测量微生物生长的产量。这项工作将测试存储在微生物基因组中的信息是否可以预测它们的发电策略，以及微生物组多样性的各个方面是否与效率有关，从而开发一个预测建模框架。如果这个基本的热力学理论可以解释从细胞到群落的生物组织模式，它将提供一个重要的新框架来预测生物学将如何应对地球上的未来条件。更广泛的影响包括让社区大学的学生参与研究，以及研究生和博士后学生。外联活动包括为一个讲故事平台制作科学视频，供公众使用。微生物和所有生物一样，通过创造熵来维持生命的秩序。它们存在于开放的、非平衡的热力学系统中，跨越自由能的梯度，为增强有效能流的结构（蛋白质、细胞、群落）的形成和维持提供燃料，同时试图最小化废热的耗散-增强过程中的整体熵产生。微生物群落的组装和演替是由有效能流驱动的，并且是最大功率和最小散热之间的权衡来调节产量（即效率）。这种对熵产生的权衡是一个基本的热力学原理。作为一种生物优化功能，功率和产量的优化通过自然选择使热力学和进化保持一致，因为资源可用性或压力等约束条件会根据其功率的放置来调节生物体的适应性：帕累托最优曲线上的产量策略。这些权衡如何在社区范围内表现出来，尚未得到实证检验。 本研究将通过（1）开发一种新型的集成纳米量热-微流体平台来控制资源和应力的梯度，同时量化开放系统中的功率、产率和熵产生;（2）进行一系列操作实验以评估微生物和微生物组的性质如何与功率、产率和熵产生以及生物（地质）化学输出相关，以及（3）开发基于功率-产率权衡的热力学的模拟工具，以预测微生物组功能和组成的出现。该热力学理论适用于所有生物体，其成果可推广到微生物组科学之外。该奖项的共同资助由材料研究部提供。该奖项反映了NSF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。

Across Earth’s ecosystems, microbes adapt and form communities (microbiomes) across gradients of energy and resource richness. Like the machines and electrical circuits we engineer, power and efficiency are key features that also determine the competitiveness of microbes in communities. Over evolutionary time, microbes have optimized their own molecular machines to convert available energy with high efficiency, minimizing the loss of waste energy as heat. Microbes have a range of strategies, reflecting the balance between the rate of new cell production (power), and its efficiency (yield), while also dealing with various costs of survival that reduce yield. This research project will test the hypothesis that microbiomes, assemble from individual members to form communities that also optimize power while increasing efficiency. This principle of power and efficiency optimization may apply generally across different levels of biological organization from proteins to ecosystems. Researchers will study microbiomes from soils and the human gut as model systems to test this idea. They will develop a new experimental platform, involving multiple compartments to control how microbiomes interact, with integrated nanotechnology sensors to measure microbial efficiency as heat output, plus advanced microscopy to measure yield as microbes grow. This work will test if information stored in microbial genomes can predict their power-yield strategies, and if aspects of microbiome diversity can be related to efficiency, developing a predictive modeling framework. If this fundamental thermodynamic theory can explain patterns in biological organization from cells to communities, it will provide an important new framework to predict how biology will respond to future conditions on Earth. Broader impacts include involving community college students in the research, in addition to graduate and postdoctoral students. Outreach activities consist of developing scientific videos for a storytelling platform, which would be available to the general public. Microbes, like all living organisms, maintain the order of life through the creation of entropy. They exist in open, non-equilibrium thermodynamic systems, across gradients of free-energy that fuel the formation and maintenance of structures (proteins, cells, communities) that enhance exergy flow, while attempting to minimize dissipation of waste heat – enhancing overall entropy production in the process. The assembly and succession of microbial communities are driven by flows of exergy, and it is the trade-off between maximum power and minimum heat dissipation that regulate yield (i.e. efficiency). This trade-off towards the production of entropy is a fundamental thermodynamic principle. As a biological optimization function, the optimization of power and yield aligns thermodynamics and evolution through natural selection, in that constraints such as resource availability or stress, modulate the fitness of an organism depending on the placement of their power:yield strategy across a Pareto optimal curve. How these trade-offs manifest at the community scale has not been empirically tested. This research will test this by (1) developing a novel integrated nanocalorimetry-microfluidics platform to control gradients of resources and stress, simultaneously quantifying power, yield and entropy production in an open system; (2) performing a series of manipulative experiments to evaluate how properties of microorganisms and microbiomes relate to power, yield and entropy production and bio(geo)chemical outputs, and (3) develop simulation tools based on the thermodynamics of power-yield trade-offs to predict the emergence of microbiome function and composition. This thermodynamic theory is applicable to all living organisms, with the outcomes being generalizable beyond microbiome sciences.Co-funding for this award was provided by the Division of Materials Research.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.