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.

该奖项寻求对微生物如何收集营养并保持可行的基本了解，同时面对地球上最极端的条件。这些生物中有许多居住在盐饱和的湖泊和池塘中，这些湖泊和池塘含量低，氧气限制为氧气。这些“ Halohiles”，域古细菌的成员可以教会我们有关能量代谢的起源，因为它们利用了各种代谢策略来在同一稀缺资源池中生存。这些卤素自然合成了独特的化学物质，例如类似于喷气燃料和可生物降解塑料的化学物质。关于卤素代谢功能的知识差距很大，已经阻止了将卤素用于替代能量解决方案。该项目将通过生成和比较80种卤素的能源生产途径的计算模型来填补这些空白。对两个测试物种的代谢产物的经验测量将用于完善模型预测。每年，PI的研究小组都会教两个为期一周的科学浸入式讲习班，一个针对高中生，另一个针对波多黎各大学的本科生。在这两个研讨会中，学生将在极端压力下测量和建模卤素活力。这项研究将提供有关能源生产发展，实现未来替代能源策略的基本知识，并在其职业生涯的早期参与STEM领域的多样化学生。该项目的长期目标是增加有关古细菌微生物的代谢途径的基本知识，如何调节环境中的营养中的营养。高盐适应的古细菌或卤素为研究转录调节和代谢网络的共同进化提供了独特的模型。成员物种具有共同的催眠栖息地，但在产生能量方面表现出广泛的多样性。在季节性变化期间，在高盐湖中，营养物质间歇性地提供。作为回应，卤素已经获得了各种可能的代谢解决方案，以在同一稀缺资源池中生存。 PI实验室的最新转录组和代谢组学证据表明，卤素使用转录调节作为主要机制，以动态地调整代谢网络，以响应营养的波动。基于这一证据，工作假设是，在营养波动期间，监管网络与代谢网络共同发展。但是，迄今为止，由于可拖动模型生物的稀缺性，古细菌的代谢多样性在很大程度上尚未探索。最近，已经有80个卤素的基因组序列，这是古细菌中前所未有的量表。使用这些基因组序列数据，将实现以下目标来检验中心假设：（a）使用自动计算方法构造和比较80种卤素的代谢网络模型； （b）在两个密切相关的，可遗传的卤素模型物种中有关营养和遗传扰动的测试模型预测； （c）使用转录组和代谢组数据作为其他约束来完善代谢模型。

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

Transcriptional Regulation in Archaea: From Individual Genes to Global Regulatory Networks

• DOI: 10.1146/annurev-genet-120116-023413
• 发表时间: 2017-01-01
• 期刊: ANNUAL REVIEW OF GENETICS, VOL 51
• 作者: Martinez-Pastor, Mar;Tonner, Peter D.;Schmid, Amy K.
• 通讯作者: Schmid, Amy K.

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