Molecular Basis of the Effects of Hydrostatic Pressure on Biomacromolecules

静水压力对生物大分子影响的分子基础

基本信息

批准号：
1803045
负责人：
George Makhatadze
金额：
$ 73.97万
依托单位：
Rensselaer Polytechnic Institute
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1803045&HistoricalAwards=false
关键词：
Molecular Basis Effects Hydrostatic Pressure

项目摘要

Professor George I. Makhatadze of Rensselaer Polytechnic Institute is supported by the Chemistry of Life Processes Program in the Division of Chemistry to develop and experimentally test models of how biomacromolecules such as proteins and DNA respond and adapt to high hydrostatic pressure. The Molecular Biophysics Cluster in the Division of Molecular and Cellular Biosciences, and the Physics of Living Systems Program in the Division of Physics also contribute to this award. Hydrostatic pressure is an important environmental variable that plays a role in biological adaptation for many extremophilic organisms - organisms that can tolerate and even thrive under extreme environmental conditions. On Earth, pressure-tolerant barophiles generally populate the deep ocean floor, where the pressures on their bodies can reach 110 MPa (~1,100 atm). This project is utilizing a combination of computational modeling and biochemical and biophysical experiments to determine the pressure-dependence of protein and nucleic acid stability in extremophilic organisms. They also examine the role of hydrostatic pressure in modulating protein-DNA interactions. The results of this project may enable prediction of pressure-dependent growth phenotypes of diverse organisms. The project may also help in the design of next-generation, environmentally-friendly catalysts and robust biomaterials. Research topics and recent findings from the lab are integrated into Professor Makhatadze's teaching as part of the Biochemistry and Biophysics major at RPI. The project engages graduate students, and high school students and undergraduates in interdisciplinary research, providing specialized training in a diverse and unique scientific skill set. The objectives of this project are to probe at the structural proteome level the differences in volumetric properties of thermophilic, psychrophilic and barophilic organisms. The research provides quantitative understanding of the effects of hydrostatic pressure on protein-DNA interactions and nucleic acids. This understanding is being achieved by uniquely combining biochemical and biophysical experiments with computational tools to interrogate and compare volume changes upon protein unfolding in specific barophilic organisms at the structural proteome level. The research team also investigates the effects of hydrostatic pressure on stability of alpha-helices, and compares model predictions against high-pressure cell measurements of volume changes due to helix-coil transitions. Dr. Makhatadze analyzes the effects of hydrostatic pressure, including hydration, on the stability of nucleic acids as the progenitor building blocks of life and investigate the effects of hydrostatic pressure on protein-DNA interactions, for comparison with high-pressure fluorescence experiments. In addition to training graduate researchers in interdisciplinary computational and experimental research at the intersection of biophysics and biochemistry, the team mentors high school and undergraduate students as active, ongoing participants in laboratory research. Outreach to minority undergraduates through summer internships are provided by the Rensselaer's Louis Stokes Alliance for Minority Participation (LSAMP) program.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.

Rensselaer理工学院的George I. Makhatadze教授得到了化学过程的化学过程计划的支持，以开发和实验测试模型，以了解诸如蛋白质和DNA之类的生物乳糖分子如何反应并适应高液压压力。分子生物科学和细胞生物科学划分的分子生物物理学集群，以及物理学划分的生物体系程序计划也有助于该奖项。静液压是一个重要的环境变量，在许多极端粒细胞生物的生物适应中起作用 - 在极端环境条件下可以耐受甚至繁殖的生物。在地球上，耐压力承受的负重通常填充深海地板，其身体上的压力可以达到110 MPa（〜1,100 atm）。该项目利用计算建模和生化和生物物理实验的结合来确定蛋白质和核酸稳定性在过度粒细胞生物中的压力依赖性。他们还检查了静液压在调节蛋白-DNA相互作用中的作用。该项目的结果可能可以预测各种生物体的压力依赖性生长表型。该项目还可能有助于设计下一代，环保的催化剂和强大的生物材料。 RPI的生物化学和生物物理学专业的一部分，将实验室的研究主题和最新发现纳入了Makhatadze教授的教学中。该项目与研究生，高中生和本科生参与跨学科研究，提供了多种独特的科学技能培训。该项目的目标是在结构蛋白质组级别探测嗜热，精神嗜和性能生物的体积特性的差异。该研究提供了对静液压对蛋白质-DNA相互作用和核酸的影响的定量理解。通过将生化和生物物理实验与计算工具相结合，以询问和比较体积变化对蛋白质在结构蛋白质组水平上的特定果皮生物中展开的蛋白质的变化，从而实现了这种理解。研究小组还研究了静水压力对α-螺旋稳定性的影响，并将模型预测与由于螺旋线圈过渡引起的体积变化的高压细胞测量结果进行了比较。 Makhatadze博士分析了包括水合在内的静水压力对核酸作为生命的祖细胞的稳定性的影响，并研究了液压压力对蛋白质-DNA相互作用的影响，以与高压荧光实验进行比较。除了培训生物物理学和生物化学交集的跨学科计算和实验研究的研究生研究人员外，团队指导了高中和本科生，作为活跃的实验室研究参与者。伦斯勒（Rensselaer）的路易斯·斯托克斯（Louis Stokes）少数群体参与计划（LSAMP）计划为少数群体的本科生提供宣传。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影响的审查标准来通过评估来获得支持的。