Molecular Basis of the Effects of Hydrostatic Pressure on Biomacromolecules

乔治教授Rensselaer Polytechnic Institute的Makhatadze得到了化学系生命过程化学项目的支持，以开发和实验测试生物大分子（如蛋白质和DNA）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学集群以及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，这些生物可以耐受极端环境条件，甚至在极端环境条件下茁壮成长。在地球上，耐压的嗜压生物通常居住在深海海底，它们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物化学及生物物理实验相结合的方法来确定极端生物体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力在调节蛋白质-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。研究课题和实验室的最新发现被整合到Makhatadze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。 该项目使研究生、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业培训。本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。这项研究提供了定量的了解流体静压对蛋白质-DNA相互作用和核酸的影响。 这种理解是通过独特的生物化学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嗜压生物中蛋白质展开后的体积变化。 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细胞测量进行了比较。 Makhatadze博士分析了静水压力（包括水合作用）对作为生命祖细胞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，以与高压荧光实验进行比较。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，该团队还指导高中和本科生积极参与实验室研究。 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大学生提供外展服务。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.