A systems biology framework to uncover rules governing robustness of a microbial community

揭示微生物群落稳健性规则的系统生物学框架

• 批准号: 2042948
• 负责人: Nitin Baliga
• 金额: $ 155.23万
• 依托单位: Institute for Systems Biology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2042948&HistoricalAwards=false
• 关键词: systems; biology; framework; uncover; rules

This project is uncovering how a microbial community adapts to changes in its environment to enable powerful biotechnology solutions, such as the production of high value commodity chemicals in a sustainable manner. Adapting to fluctuations in resource availability is an energetically expensive process for a microbial community, requiring the modulation of hundreds to thousands of genes. This project is characterizing the molecular and cellular networks of a microbial community that drive this adaptive process. Activities in this project are using a systems biology approach to study a microbial community as a whole. Specifically, using modern sequencing technologies this project is investigating how controlled environmental fluctuations induce changes in the expression of all genes of a synthetic microbial community of two organisms that play a central role across diverse environments, including lake sediment, soil, and the human gut, contributing to a biogeochemically important process of cycling 1 gigaton of carbon annually. By developing innovative computational modeling technologies these data are being analyzed to uncover how regulatory networks drive the dynamic community-wide gene expression changes, to coordinate flux changes through metabolic pathways, and ultimately manifest in overall improved fitness of the community. In so doing, this project is generating a predictive and mechanistic understanding of the adaptive processes of a microbial community. Hypotheses based on the predictive and mechanistic understanding of the adaptive process are being tested using targeted genetic and environmental manipulation of the cellular and molecular networks of the community. The research capabilities, predictive models, and knowledge being generated in this project are widely applicable to research and biotechnology programs in the public and private sectors, including projects across the MCB and IOS Divisions of NSF. To ascertain wide outreach, this project is leveraging a long-term NSF-funded effort to engage women, minorities, and disadvantaged students and teachers, to bring current science concepts and practices generated by this project into high school classrooms. Curricula developed in this project are being disseminated across all 50 states in the US and across 100 countries worldwide.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.

该项目正在揭示微生物社区如何适应其环境变化，以实现强大的生物技术解决方案，例如以可持续的方式生产高价值商品化学物质。对于微生物群落来说，适应资源可用性的波动是一个昂贵的过程，需要调节数百至数千个基因。该项目正在表征驱动这种适应过程的微生物群落的分子和细胞网络。该项目中的活动正在使用系统生物学方法来整体研究微生物社区。具体而言，使用现代测序技术，该项目正在研究控制环境波动如何引起两个生物的合成微生物群落的所有基因的表达变化，这些生物具有两个生物的核心，这些生物在各种环境中都起着核心作用，包括湖泊的沉积物，土壤和人类肠道，为生物地球化学在生物学上的重要过程，从而有助于1 Gigaton of Carbone carbone of Carbone Annimalimallimallimallimallimallimallimallimallime corbone corbone。通过开发创新的计算建模技术，正在分析这些数据，以发现监管网络如何驱动动态范围的社区范围的基因表达变化，以通过代谢途径来协调通量变化，并最终体现在社区的整体适应性中。这样一来，这个项目正在对微生物群落的适应过程产生预测和机械理解。基于对自适应过程的预测和机理理解的假设正在使用社区细胞和分子网络的靶向遗传和环境操纵进行测试。该项目中产生的研究能力，预测模型和知识广泛适用于公共和私营部门的研究和生物技术计划，包括NSF的MCB和iOS部门的项目。为了确定广泛的宣传，该项目正在利用长期的NSF资助的努力来吸引妇女，少数民族和弱势学生和老师，以将该项目产生的当前科学概念和实践带入高中教室。该项目开发的课程正在美国和全球所有100个国家 /地区的所有50个州进行传播。该奖项反映了NSF的法定任务，并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标准通过评估来支持的。

项目成果

Transcriptome signature of cell viability predicts drug response and drug interaction in Mycobacterium tuberculosis.

• DOI: 10.1016/j.crmeth.2021.100123
• 发表时间: 2021-12-20
• 期刊: Cell reports methods
• 作者: Srinivas V;Ruiz RA;Pan M;Immanuel SRC;Peterson EJR;Baliga NS
• 通讯作者: Baliga NS

Disrupting the ArcA Regulatory Network Amplifies the Fitness Cost of Tetracycline Resistance in Escherichia coli.

• DOI: 10.1128/msystems.00904-22
• 发表时间: 2023-02-23
• 期刊: mSystems
• 影响因子: 6.4

Reconsidering the in vivo functions of Clostridial Stickland amino acid fermentations.

• DOI: 10.1016/j.anaerobe.2022.102600
• 发表时间: 2022-08
• 期刊: ANAEROBE
• 影响因子: 2.3
• 作者: Pavao, Aidan;Graham, Madeline;Arrieta-Ortiz, Mario L;Immanuel, Selva Rupa Christinal;Baliga, Nitin S;Bry, Lynn
• 通讯作者: Bry, Lynn

Predictive regulatory and metabolic network models for systems analysis of Clostridioides difficile.

• DOI: 10.1016/j.chom.2021.09.008
• 发表时间: 2021-11-10
• 期刊: Cell host & microbe
• 影响因子: 30.3
• 作者: Arrieta-Ortiz ML;Immanuel SRC;Turkarslan S;Wu WJ;Girinathan BP;Worley JN;DiBenedetto N;Soutourina O;Peltier J;Dupuy B;Bry L;Baliga NS
• 通讯作者: Baliga NS

Quantitative prediction of conditional vulnerabilities in regulatory and metabolic networks using PRIME.

• DOI: 10.1038/s41540-021-00205-6
• 发表时间: 2021-12-06
• 期刊: NPJ systems biology and applications
• 影响因子: 4
• 作者: Immanuel SRC;Arrieta-Ortiz ML;Ruiz RA;Pan M;Lopez Garcia de Lomana A;Peterson EJR;Baliga NS
• 通讯作者: Baliga NS