Biophysics of protein nucleic-acids interactions
蛋白质核酸相互作用的生物物理学
基本信息
- 批准号:1105458
- 负责人:
- 金额:$ 25.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-09-15 至 2015-08-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
TECHNICAL SUMMARYThe Division of Materials Research and the Division of Molecular and Cellular Biosciences contribute funds to make this award. This award supports theoretical research and education in the field of molecular mechanisms of protein nucleic-acid interactions. Nucleic acids (DNA and RNA) and proteins are some of the fundamental molecules of living systems. In a living organism they perform their biological function based on their interactions with each other. The overarching goal of the research under this award is to develop theoretical models of the complex phenomena resulting from these interactions. The research will be in close collaborations with experimentalists resulting in immediate feedback between model building and experiments and thus leading to a deep understanding of the biological phenomena of interest based on molecular mechanisms. There are three specific phenomena that will be studied:1. As cells repair damage to their DNA they have to clear the stretch of DNA to be repaired from associated proteins such as transcription factors and histones. For DNA mismatch repair this is the function of the protein complex MSH2/MSH6 which forms a sliding clamp on the DNA in the vicinity of a mismatch. Quantitative models developed under this award will reveal the detailed molecular mechanism underlying this clearing of DNA through binding of MSH2/MSH6.2. When retroviruses, such as HIV, infect a cell, they use a special protein to 'soften' the secondary structures of their RNA genome and enable several molecular processes that are necessary for successful host infection. Under this award a quantitative model will be developed to explain how nucleocapsid and similar RNA binding proteins change the secondary structure of RNA molecules and its dynamics and how these structural changes affect the processes necessary for retroviral infection.3. RNA molecules can be threaded through protein and artificial nanopores that are so small that only a single strand of the molecule can pass through them. Thus, the secondary structure of these molecules has to unravel in order for the molecule to pass through the pore. This makes nanopore translocation experiments a unique vehicle to study RNA secondary structure kinetics. However, this requires molecular scale models of RNA structure kinetics and interactions with the nanopore which will be developed under this award.The research and educational activities will provide a highly interdisciplinary training to graduate and undergraduate students through various avenues such as direct involvement in the research and participation in biophysics courses and seminars. The scientific impact of the models developed under this award will be maximized by incorporating these models into existing or newly developed web servers.NON-TECHNICAL SUMMARYThe Division of Materials Research and the Division of Molecular and Cellular Biosciences contribute funds to make this award. This award supports theoretical research and education in the physics of biological molecules. There are three major classes of molecules that life is based upon, namely proteins, nucleic acids (DNA and RNA), and lipids. These different types of molecules have their distinct roles, but in order for a living cell to function they all have to work together. The research under this award specifically focuses on the interplay between proteins and nucleic acid molecules. The overarching goal is to develop theoretical models of the complex phenomena that arise as proteins and nucleic acids interact. These models in turn will allow the interpretation of experiments and enable a deep understanding of diverse biological phenomena. The specific phenomena of interest here are how cells correct errors in their DNA in order to avoid cancer, how retroviruses (such as HIV) infect a host cell, and how RNA molecules pass through minuscule holes and reveal their dynamical properties.The research and educational activities will involve training graduate and undergraduate students at the frontiers of research at the interdisciplinary interface between the life and the physical sciences. All projects will be performed in close collaborations with experimentalists thereby providing a unique training environment to the students involved in the research. In addition, the models developed in the course of this research will be disseminated through interactive web pages in order to enable their utility to as broad a group of users as possible.
技术总结材料研究部和分子和细胞生物科学部为颁发这一奖项提供资金。该奖项支持蛋白质核酸相互作用的分子机制领域的理论研究和教育。核酸(DNA和RNA)和蛋白质是生命系统的一些基本分子。在活着的有机体中,它们基于彼此的相互作用来执行它们的生物功能。该奖项下的研究的首要目标是开发由这些相互作用产生的复杂现象的理论模型。这项研究将与实验者密切合作,在建模和实验之间产生即时反馈,从而导致对基于分子机制的感兴趣的生物学现象的深入理解。有三种特殊的现象将被研究:1.当细胞修复DNA损伤时,他们必须从转录因子和组蛋白等相关蛋白质中清除要修复的DNA片段。对于DNA错配修复,这是蛋白质复合体MSH2/MSH6的功能,它在错配附近的DNA上形成一个滑动夹子。根据该奖项开发的定量模型将揭示通过结合MSH2/MSH6.2清除DNA的详细分子机制。当逆转录病毒,如艾滋病毒,感染细胞时,它们使用一种特殊的蛋白质来‘软化’其RNA基因组的二级结构,并启动几个成功感染宿主所必需的分子过程。根据这一奖项,将开发一个定量模型来解释核衣壳和类似的RNA结合蛋白如何改变RNA分子的二级结构及其动力学,以及这些结构变化如何影响逆转录病毒感染所必需的过程。RNA分子可以穿过蛋白质和人造纳米孔,这些纳米孔如此之小,以至于只有一条分子可以穿过它们。因此,这些分子的二级结构必须解体,才能使分子通过孔洞。这使得纳米孔移位实验成为研究RNA二级结构动力学的独特工具。然而,这需要在该奖项下开发RNA结构动力学和与纳米孔相互作用的分子尺度模型。研究和教育活动将通过各种途径为研究生和本科生提供高度跨学科的培训,如直接参与研究和参与生物物理学课程和研讨会。根据该奖项开发的模型的科学影响将通过将这些模型整合到现有的或新开发的网络服务器中而最大化。非技术总结材料研究司和分子与细胞生物科学部为颁发该奖项提供资金。该奖项支持生物分子物理学的理论研究和教育。生命的基础主要有三类分子,即蛋白质、核酸(DNA和RNA)和脂类。这些不同类型的分子有其不同的作用,但为了让活细胞发挥作用,它们都必须共同工作。该奖项的研究重点是蛋白质和核酸分子之间的相互作用。首要目标是为蛋白质和核酸相互作用时出现的复杂现象开发理论模型。这些模型反过来将允许对实验进行解释,并使人们能够深入了解各种生物现象。这里感兴趣的具体现象包括细胞如何纠正DNA中的错误以避免癌症,逆转录病毒(如艾滋病毒)如何感染宿主细胞,以及RNA分子如何通过微小的孔洞并揭示其动力学性质。研究和教育活动将涉及在生命科学和物理学之间的交叉学科界面上培养研究生和本科生。所有项目都将与实验者密切合作,从而为参与研究的学生提供一个独特的培训环境。此外,在本研究过程中开发的模型将通过互动网页传播,以使其效用尽可能广泛地惠及用户群体。
项目成果
期刊论文数量(0)
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Ralf Bundschuh其他文献
Single-molecule Studies of RNA Unzipping Kinetics Using Nanopores
- DOI:
10.1016/j.bpj.2008.12.2949 - 发表时间:
2009-02-01 - 期刊:
- 影响因子:
- 作者:
Jianxun Lin;Ralf Bundschuh;Amit Meller - 通讯作者:
Amit Meller
Asymmetric exclusion process and extremal statistics of random sequences.
随机序列的不对称排除过程和极值统计。
- DOI:
10.1103/physreve.65.031911 - 发表时间:
1999 - 期刊:
- 影响因子:0
- 作者:
Ralf Bundschuh - 通讯作者:
Ralf Bundschuh
Ralf Bundschuh的其他文献
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{{ truncateString('Ralf Bundschuh', 18)}}的其他基金
Quantitative modeling of nucleic acid-protein interactions
核酸-蛋白质相互作用的定量模型
- 批准号:
1719316 - 财政年份:2017
- 资助金额:
$ 25.9万 - 项目类别:
Standard Grant
Cooperativity in Nucleic-Acid Protein Interactions
核酸-蛋白质相互作用中的协同性
- 批准号:
1410172 - 财政年份:2014
- 资助金额:
$ 25.9万 - 项目类别:
Continuing Grant
Conference: 2007 Rustbelt RNA Meeting being held October 19-20, 2007 in Mt. Sterling, Ohio
会议:2007 Rustbelt RNA 会议于 2007 年 10 月 19 日至 20 日在俄亥俄州斯特林山举行
- 批准号:
0739830 - 财政年份:2007
- 资助金额:
$ 25.9万 - 项目类别:
Standard Grant
Statistical Physics Approaches to RNA Editing
RNA 编辑的统计物理方法
- 批准号:
0706002 - 财政年份:2007
- 资助金额:
$ 25.9万 - 项目类别:
Continuing Grant
Statistical Mechanics of Biological Sequence Analysis
生物序列分析的统计力学
- 批准号:
0404615 - 财政年份:2004
- 资助金额:
$ 25.9万 - 项目类别:
Continuing Grant
Iterative Hybrid Alignment: Improving the Sensitivity of Biological Database Searches
迭代混合比对:提高生物数据库搜索的灵敏度
- 批准号:
0317335 - 财政年份:2003
- 资助金额:
$ 25.9万 - 项目类别:
Continuing Grant
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