Collaborative Research: Transcriptional Adaptation and Response to Pressure

合作研究：转录适应和对压力的反应

• 批准号: 2019471
• 负责人: Catherine Royer
• 金额: $ 83.73万
• 依托单位: Rensselaer Polytechnic Institute
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2019471&HistoricalAwards=false
• 关键词: Collaborative; Research; Transcriptional; Adaptation; Response

The Earth’s deep oceans are home to an enormous amount and diversity of living creatures, including ~90% of the microbes, which can experience pressures as high as 1000 times that on the surface. The protein machines responsible for critical life processes, such as transcription of the genetic code, must be adapted to function under such extreme and inhospitable conditions. The mechanisms of this adaptation remain a mystery. This project is aimed at understanding molecular mechanisms underlying the response and adaptation to high pressure of the transcription machinery of surface- and pressure-adapted microorganisms. Better knowledge of these mechanisms will provide insights into the evolution and even the origins of life on Earth, and enable new biotechnological advances in the food science industry, e.g., to improve the safety of pressure pasteurization. Graduate students and postdoctoral scholars involved in the project will be trained in multidisciplinary research skills, and have the opportunity to mentor undergraduates and high school students. All trainees will participate in a Research Coordination Network on Extreme Biology and Biophysics.In the mesophile, Escherichia coli, and in the moderate piezophile, Photobacterium profundum SS9, the molecular basis of transcriptional response and adaptation to pressure involves the heat shock response system. High pressure induces a heat shock response in E. coli, and conversely, low pressure induces a heat shock response P. profundum SS9. The research will investigate pressure effects on promoter interactions of the transcriptional regulators of housekeeping and stress response RNA polymerase sigma factors, as well as the stability of the sigma factor proteins themselves. These responses will be characterized in P. profundum SS9 and a pressure-adapted strain of E. coli for comparative analysis. The ToxR/ToxS transcriptional regulator system, which is implicated in pressure regulation of the transcriptional program in P. profundum SS9, will also be examined. The research will involve direct observation and quantification of transcriptional protein properties and processes, using newly developed fluorescence microscopy techniques under pressure, and will employ stochastic modeling for deeper insights into the pressure sensitivity of specific biochemical steps in these processes. The project outcomes are expected to provide insights into evolutionary adaptation to high pressure environments on Earth and may help to mitigate problems caused by pressure resistant microorganisms in the food industry.This project is jointly funded by the Genetic Mechanisms and Molecular Biophysics programs of the Molecular and Cellular Biosciences Division in the Biological Sciences Directorate, and the Biological Oceanography program of the Ocean Sciences Division in the Geosciences Directorate.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.

地球的深海是生物的数量和多样性，其中包括约90％的微生物，其压力可能高达1000倍。负责关键生命过程的蛋白质机器（例如遗传密码的转录）必须在如此极端和荒凉的条件下进行调整。这种适应的机制仍然是一个谜。该项目的目的是理解反应和适应表面和压力适应微生物的转录机制的基础的分子机制。对这些机制的更好了解将提供有关地球上生命的进化甚至起源的见解，并使食品科学行业的新生物技术进步，例如提高压力巴氏灭菌的安全性。参与该项目的研究生和博士后学者将接受多学科研究技能的培训，并有机会指导本科生和高中生。所有受训者将参加有关极端生物学和生物物理学的研究协调网络。在中粒，大肠杆菌中，以及现代的Pilecophile，Profundum SS9，这是转录反应的分子基础，适应压力涉及热激反应系统。高压在大肠杆菌中诱导热冲击反应，相反，低压诱导热休克响应P. podundum SS9。该研究将研究对管家和应力反应RNA聚合酶Sigma因子的转录调节剂的启动子相互作用的压力影响，以及Sigma因子蛋白本身的稳定性。这些反应将在P. podundum ss9和大肠杆菌的压力适应菌株中进行比较分析。也将检查在P. profundum SS9中的转录程序压力调节中实施的Toxr/ToxS转录调节器系统。这项研究将涉及使用新开发的荧光显微镜技术在压力下进行转录蛋白质和过程的直接观察和定量，并将采用随机建模，以深入了解这些过程中特定生物化学步骤的压力敏感性。预计该项目结果将提供对地球上高压环境的进化适应的见解，并可能有助于缓解食品工业中耐压微生物引起的问题。该项目由遗传机制和分子生物物理学计划共同资助了分子和细胞生物科学在生物科学方面的遗传机制和分子生物物理学计划，该计划在生物科学方面的海洋局部和海洋研究方面的海洋学局局长，该计划在海洋学局部局部研究，并在生物科学方面划分了海洋学局部，该计划在海洋学方面统一了海洋学局部，该计划在海洋学局部局部研究，该计划在海洋学局部局部，并具有海洋学的分区。该奖项反映了NSF的法定任务，并通过使用基金会的知识分子优点和更广泛的影响审查标准来评估值得支持。