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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.

伦斯勒理工学院的George I.Makhatadze教授得到化学系生命过程化学项目的支持，开发并实验测试蛋白质和DNA等生物大分子如何响应和适应高静水压力的模型。分子和细胞生物科学部的分子生物物理组和物理学部的生命系统物理学项目也为该奖项做出了贡献。静水压力是一个重要的环境变量，在许多极端生物的生物适应中发挥作用--极端环境条件下能够容忍甚至茁壮成长的生物。在地球上，耐压的耐压生物通常生活在深海海底，他们身体上的压力可以达到110兆帕(~1100大气压)。该项目利用计算机模拟以及生化和生物物理实验相结合的方法来确定极端微生物中蛋白质和核酸的稳定性与压力的关系。他们还研究了静水压力在调节蛋白质-DNA相互作用中的作用。该项目的结果可能使预测不同生物的压力依赖生长表型成为可能。该项目还可能有助于设计下一代环境友好型催化剂和坚固的生物材料。该实验室的研究主题和最新发现被整合到马哈塔泽教授的教学中，作为RPI生物化学和生物物理学专业的一部分。该项目让研究生、高中生和本科生参与跨学科研究，提供多样化和独特的科学技能方面的专门培训。本项目的目标是在结构蛋白质组水平上探索嗜热、嗜冷和嗜压生物体体积性质的差异。这项研究提供了对静水压力对蛋白质-DNA相互作用和核酸影响的定量理解。这一理解是通过独特地将生化和生物物理实验与计算工具相结合来实现的，以在结构蛋白质组水平上询问和比较特定耐压生物中蛋白质展开时的体积变化。研究小组还研究了静水压力对α-螺旋稳定性的影响，并将模型预测与高压室测量的螺旋-线圈转变的体积变化进行了比较。马哈塔泽博士分析了包括水合作用在内的静水压力对作为生命始祖的核酸稳定性的影响，并研究了静水压力对蛋白质-DNA相互作用的影响，并与高压荧光实验进行了比较。除了在生物物理学和生物化学的交叉点培训跨学科计算和实验研究的研究生研究人员外，该团队还指导高中生和本科生积极、持续地参与实验室研究。伦斯勒的路易斯·斯托克斯少数族裔参与联盟(LSAMP)计划通过暑期实习向少数族裔本科生提供外展服务。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。