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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 教授在化学系生命过程化学项目的支持下，开发和实验测试蛋白质和 DNA 等生物大分子如何响应和适应高静水压的模型。分子和细胞生物科学部的分子生物物理学集群以及物理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，在许多极端生物体的生物适应中发挥着重要作用，这些生物体可以耐受甚至在极端环境条件下繁衍生息。在地球上，耐压嗜压生物通常生活在深海海底，其身体承受的压力可达 110 兆帕（约 1,100 个大气压）。该项目正在利用计算模型与生化和生物物理实验相结合来确定极端微生物中蛋白质和核酸稳定性的压力依赖性。他们还研究了静水压在调节蛋白质-DNA 相互作用中的作用。该项目的结果可以预测不同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催化剂和坚固的生物材料。作为 RPI 生物化学和生物物理学专业的一部分，实验室的研究主题和最新发现被纳入 Makhatadze 教授的教学中。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的专门培训。该项目的目标是在结构蛋白质组水平上探讨嗜热、嗜冷和嗜压生物体体积特性的差异。该研究定量地了解了静水压对蛋白质-DNA 相互作用和核酸的影响。这种理解是通过将生化和生物物理实验与计算工具独特地结合起来来实现的，以在结构蛋白质组水平上询问和比较特定嗜压生物体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，并将模型预测与螺旋-螺旋转变引起的体积变化的高压单元测量结果进行比较。 Makhatadze 博士分析了静水压（包括水合作用）对作为生命祖细胞构件的核酸稳定性的影响，并研究了静水压对蛋白质-DNA 相互作用的影响，以便与高压荧光实验进行比较。除了在生物物理学和生物化学交叉领域培训研究生研究人员进行跨学科计算和实验研究外，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。