Modeling the function and evolution of metabolic networks across hypersaline-adapted Archaea

对适应高盐古菌的代谢网络的功能和进化进行建模

• 批准号: 1615685
• 负责人: Amy Schmid
• 金额: $ 75万
• 依托单位: Duke University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2020-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1615685&HistoricalAwards=false
• 关键词: Modeling; function; evolution; metabolic; networks

This award, seeks fundamental understanding of how microorganisms gather nutrients and remain viable while facing the most extreme conditions on Earth. Many of these organisms reside in salt saturated lakes and ponds that are low in nutrients and limited for oxygen. These "halophiles", members of the domain Archaea, can teach us about the origins of energy metabolism since they exploit a wide array of metabolic strategies to survive on the same pool of scarce resources. These halophiles naturally synthesize unique chemicals, such as those resembling jet fuel and biodegradable plastic. Large gaps in knowledge regarding halophile metabolic functions have prevented the use of halophiles for alternative energy solutions. This project will fill these gaps by generating and comparing computational models of energy production pathways across 80 species of halophiles. Empirical measurements of metabolic products from two test species will be used to refine the model predictions. Each year, the PI's research group will teach two weeklong science immersion workshops, one for high school students and the other for undergraduates at University of Puerto Rico. In both workshops, students will measure and model halophile viability during extreme stress. This research will provide fundamental knowledge regarding the evolution of energy production, enable future alternative energy strategies, and engage a diverse population of students in STEM fields early in their careers.The long-term goal of this project is to increase fundamental knowledge regarding how metabolic pathways of archaeal microorganisms are regulated in response to varying nutrients in the environment. Hypersaline-adapted Archaea, or halophiles, provide a unique model for investigating the co-evolution of the transcription regulatory and metabolic networks. Member species share a common hypersaline habitat, but exhibit extensive diversity in how they generate energy. Nutrients are intermittently available in hypersaline lakes during seasonal variations. In response, halophiles have acquired a wide array of possible metabolic solutions to survive on the same pool of scarce resources. Recent transcriptomic and metabolomics evidence from the PI's lab suggest that halophiles use transcriptional regulation as a primary mechanism to tune the metabolic network dynamically in response to nutrient fluctuations. Based on this evidence, the working hypothesis is that the regulatory network co-evolves with the metabolic network in diverse ways during nutrient fluctuation. However, to date, archaeal metabolic diversity has been largely unexplored due to the scarcity of tractable model organisms. Recently, 80 genome sequences of halophiles have become available, a scale that is unprecedented among Archaea. Using these genomic sequence data, the following objectives will be carried out to test the central hypothesis: (a) Construct and compare metabolic network models for 80 species of halophiles using automated computational methods; (b) Test model predictions regarding nutrient and genetic perturbations in two closely related, genetically tractable halophile model species; (c) Refine metabolic models using transcriptome and metabolome data as additional constraints.

该奖项旨在从根本上了解微生物如何在地球上最极端的条件下收集营养并保持活力。许多这些生物居住在盐饱和的湖泊和池塘中，这些湖泊和池塘营养物质含量低，氧气有限。这些“嗜盐生物”，域的成员，可以教我们关于能量代谢的起源，因为他们利用各种各样的代谢策略在同一个稀缺资源池中生存。这些嗜盐生物自然合成独特的化学物质，如类似喷气燃料和生物降解塑料的化学物质。关于嗜盐菌代谢功能的知识的巨大差距阻碍了嗜盐菌用于替代能源解决方案。该项目将通过生成和比较80种嗜盐生物的能量生产途径的计算模型来填补这些空白。将使用两种试验种属代谢产物的经验测量值来完善模型预测。每年，PI的研究小组将教授两个为期一周的科学沉浸式研讨会，一个为高中生，另一个为波多黎各大学的本科生。在这两个研讨会中，学生将测量和模拟极端压力下嗜盐菌的生存能力。这项研究将提供有关能源生产演变的基础知识，使未来的替代能源战略，并在他们的职业生涯早期从事STEM领域的学生的多元化人口。该项目的长期目标是增加有关古菌微生物的代谢途径如何响应环境中不同的营养物质调节的基础知识。高盐适应的盐藻或嗜盐生物为研究转录调控和代谢网络的共同进化提供了一个独特的模型。成员物种共享一个共同的高盐栖息地，但在如何产生能量方面表现出广泛的多样性。在季节变化期间，高盐度湖泊中的营养盐是间歇性的。作为回应，嗜盐生物已经获得了广泛的可能的代谢解决方案，以在同一个稀缺资源池中生存。最近来自PI实验室的转录组学和代谢组学证据表明，嗜盐菌使用转录调控作为主要机制来动态调整代谢网络以应对营养波动。基于这一证据，工作假设是，在营养波动期间，调节网络以不同的方式与代谢网络共同进化。然而，到目前为止，古菌代谢多样性在很大程度上尚未探索，由于缺乏易处理的模式生物。最近，80个嗜盐生物的基因组序列已经公布，这在海洋生物中是前所未有的。利用这些基因组序列数据，将实现以下目标，以检验中心假设：（a）利用自动计算方法，为80种嗜盐生物构建和比较代谢网络模型;（B）在两种密切相关、遗传上易处理的嗜盐生物模式物种中，检验关于营养和遗传扰动的模型预测;（c）使用转录组和代谢组数据作为额外的限制因素，完善代谢模型。

项目成果

N-glycosylation is important for Halobacterium salinarum archaellin expression, archaellum assembly, and cell motility.

N-糖基化对于盐杆菌古菌蛋白表达、古菌组装和细胞运动非常重要。

• DOI: 10.3389/fmicb.2019.01367
• 发表时间: 2019
• 期刊: Frontiers in microbiology
• 影响因子: 5.2
• 作者: Zaretsky, M.

SnapShot: Microbial Extremophiles

• DOI: 10.1016/j.cell.2020.01.018
• 发表时间: 2020-02
• 期刊: Cell
• 影响因子: 64.5
• 作者: Amy K. Schmid;T. Allers;J. DiRuggiero

Synergistic Impacts of Organic Acids and pH on Growth of Pseudomonas aeruginosa: A Comparison of Parametric and Bayesian Non-parametric Methods to Model Growth

• DOI: 10.3389/fmicb.2018.03196
• 发表时间: 2019-01-08
• 期刊: FRONTIERS IN MICROBIOLOGY
• 影响因子: 5.2
• 作者: Bushell, Francesca M. L.;Tunner, Peter D.;Lund, Peter A.
• 通讯作者: Lund, Peter A.

GlpR Is a Direct Transcriptional Repressor of Fructose Metabolic Genes in Haloferax volcanii

• DOI: 10.1128/jb.00244-18
• 发表时间: 2018-06
• 期刊: Journal of Bacteriology
• 影响因子: 3.2
• 作者: Jonathan H. Martin;Katherine Sherwood Rawls;J. C. Chan;Sungmin Hwang;M. Martínez-Pastor;Lana J. McMillan;Laurence Prunetti;Amy K. Schmid;J. Maupin-Furlow