Understanding Gene Regulatory Network Function During Stress Response Adaptation of an Archael Extremophile

了解古细菌极端微生物应激反应适应过程中的基因调控网络功能

• 批准号: 1052290
• 负责人: Amy Schmid
• 金额: $ 80.04万
• 依托单位: Duke University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1052290&HistoricalAwards=false
• 关键词: Understanding; Gene; Regulatory; Network; Function

Understanding gene regulatory network function during stress response adaptation of an archaeal extremophileIntellectual merit: Although life science research has entered the post-genomic era, we still understand little about the diversity of microbial life on earth. Information is particularly lacking on microbial extremophiles, which thrive at the limits of life, in deep-sea hydrothermal vents under high pressure and temperature, saturated salt lakes, and polar icecaps. Many of these organisms are members of the third domain of life, the archaea. Although archaea contribute substantially to global carbon and energy cycles, they remain understudied because they are difficult to culture and genetically manipulate. How do these microorganisms cope with an extreme and changing environment? How do they alter their genetic programs and metabolic pathways to adapt and survive changes in their unique habitats on earth? These questions are particularly relevant today, as climate change rapidly alters the conditions that support life across the globe. The impact of such changes on the microbial communities responsible for global carbon and energy cycling is unclear, but is expected to have enormous implications for human society. To address these issues, the long-term goal of the proposed research is to understand how organisms maintain homeostasis in the face of fluctuating environmental conditions. Central to this process are gene regulatory networks (GRNs) composed of groups of regulatory proteins that switch genes on and off in response to environmental stimuli. Upon sensing a change in the environment, GRNs promote the production proteins that repair damage, restore the cell to a healthy state and prepare it for future stress conditions. The Halobacterium salinarum studied in this research thrives in high salt environments. This organism is a stress response specialist, capable of surviving in the Great Salt Lake during strong daily fluctuations of light, heat, oxygen, and nutrients at extreme salt concentrations. In response, the organism shifts its metabolism between four light- and oxygen-dependent energy-generating modes. The aim of the proposed work is to determine how the organism uses GRNs,or gene circuitries, to adapt to the dynamic alterations in light, oxygen, and nutrients to ensure survival. This research will employ an innovative systems biology approach, which combines cutting-edge high throughput experimental techniques with computational and statistical modeling. Halobacterium is a good model system for studying archaeal extremophiles because it is easy to culture and genetically manipulate. What we learn about the genetic circuitry of Halobacterium will be readily applicable toward mapping the genetic circuits of other archaea. Moreover, it will provide a deeper understanding of the dynamics of microbial GRNs and expression patterns in response to changing environmental conditions. More generally, the outcome of this research will lay the foundation for understanding microbial energy production and global carbon cycling in response to climate change. Broader impacts:The research will contribute to education, training, and outreach at the high school, undergraduate, and graduate levels. Specifically, students at all levels will have training opportunities at the interface of mathematics and biology. First, the PI and lab members will teach a week-long mini course for students from North Carolina School of Science and Math, a public high school in Durham, NC that draws the top students each year from each of the congressional districts in North Carolina. Second, outreach research opportunities associated with the project will be provided for undergraduates from North Carolina universities that serve underrepresented groups through established summer programs at Duke (e.g. North Carolina Central University, Fayetteville State University). Third, a graduate student funded on the project will receive next generation interdisciplinary training at the interface of mathematics and biology.

了解基因调节网络功能在压力反应适应的适应性的古细胞素质优点：尽管生命科学研究已经进入了基因组时代，但我们仍然对地球上微生物生命的多样性了解一无所知。在高压和温度，饱和盐湖和极地冰op的深海水热通风孔中，在生命范围内繁衍生息的微生物极端细胞尤其缺乏信息。这些生物中有许多是生命的第三个领域的成员，即古细菌。尽管古细菌对全球碳和能源周期做出了重大贡献，但由于它们难以培养和遗传操纵，因此它们仍然对其进行研究。这些微生物如何应对极端和不断变化的环境？他们如何改变其遗传程序和代谢途径以适应和生存地球上独特栖息地的变化？今天，这些问题尤其重要，因为气候变化迅速改变了支持全球生活的条件。这种变化对负责全球碳和能量循环的微生物群落的影响尚不清楚，但预计对人类社会具有巨大影响。为了解决这些问题，拟议的研究的长期目标是了解面对环境波动的情况如何保持体内平衡。该过程的核心是由基因调节网络（GRN）组成，该基因由调节蛋白组组成，这些调节蛋白会响应环境刺激而开关和关闭基因。感觉到环境发生变化后，GRN促进了修复损害的生产蛋白，将细胞恢复到健康状态，并为将来的压力状况做好准备。在高盐环境中，在这项研究中研究的盐酸盐研究蓬勃发展。这种有机体是一位应力反应专家，能够在极端盐浓度下的光，热，氧气和养分的强烈每日波动中存活。作为回应，生物体将其代谢转移在四种依赖性和氧依赖性能量生成模式之间。拟议工作的目的是确定生物体如何使用GRN或基因循环来适应光，氧气和营养中的动态变化以确保生存。这项研究将采用创新的系统生物学方法，该方法将尖端高通量实验技术与计算和统计建模相结合。盐杆菌是研究古细界粒子的良好模型系统，因为它易于培养和遗传操纵。我们对盐杆菌的遗传回路的了解很容易适用于映射其他古细菌的遗传回路。此外，它将对微生物GRN和表达模式的动力学有更深入的了解，以响应不断变化的环境条件。更笼统地，这项研究的结果将奠定基础，以理解微生物能量生产和全球碳循环，以应对气候变化。更广泛的影响：这项研究将在高中，本科和研究生水平上有助于教育，培训和外展。具体来说，各个级别的学生将在数学和生物学的界面上获得培训机会。首先，PI和实验室成员将为北卡罗来纳州科学与数学学院的学生教一周的迷你课程，北卡罗来纳州达勒姆市的一所公立高中，每年都从北卡罗来纳州的每个国会区吸引顶级学生。其次，将为北卡罗来纳州大学的本科生提供与该项目相关的外展研究机会，这些大学通过在杜克大学（例如北卡罗来纳州中学，费耶特维尔州立大学）建立的夏季计划来为代表性不足的群体提供服务。第三，该项目资助的研究生将在数学和生物学界面接受下一代跨学科培训。