CAREER: Investigations of RNA Folding: A Combinatorial Approach to Thermodynamics
职业:RNA 折叠的研究:热力学的组合方法
基本信息
- 批准号:9984129
- 负责人:
- 金额:$ 49.55万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-05-01 至 2006-07-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
9984129Bevilacqua Nucleic acids (NA) are polymers consisting of four building blocks--A, C, G, and T (or U) bases--attached in a linear fashion like beads on a string. Naturally occurring nucleic acids can be formally divided into two types, DNA and RNA, based on subtle differences of a single oxygen atom or methyl (CH3) group. Two fundamental functions essential to life are the storage of genetic information that determines an individual's identity, and the increase in the rate and specificity of chemical reactions essential to life, for example in metabolism and replication. In the cell, DNA is used to store genetic information, while proteins act as enzymes to accelerate reaction rates. Strikingly, RNA can both store genetic information, as evidenced by certain viruses such as HIV-1 which causes AIDS, and act as an enzyme, with RNA enzymes referred to as "ribozymes". These properties implicate RNA in a wide variety of biological processes and diseases, making the structures and functions of RNA of significant interest. Furthermore, RNA has been implicated as an important molecule in prebiotic chemistry and the origin of life, since RNA potentially solves the "chicken and egg problem" of which came first, enzymes or genetic information. The functional properties of RNA arise from a wide range of complex three-dimensional structures. Research described in this proposal has as its primary goal understanding how RNA folds into these structures. The sequences of RNA, or the order in which the four bases occur, can be readily obtained. For example, sequencing of the genomes of approximately 25 different organisms has been completed, and sequencing of the human genome with 3 billion DNA bases is expected to be completed in the next five years. To understand the function of these RNAs, structural models are indispensable, and computer methods to predict structures are essential for keeping pace with sequencing projects. The PI's laboratory is working to obtain rules for computer prediction using a novel methodology. Investigators are developing a combinatorial approach in which a collection of molecules containing up to a million billion different sequences are prepared and then separated in a single experiment according to thermodynamic stability, or the resistance of the structure to heat denaturation. Separations are on a gel electrophoresis apparatus containing a temperature gradient (TGGE). Exceptionally stable and unstable sequences will be isolated and identified by cloning and sequencing, and rules for structure prediction obtained by further physical characterization of selected sequences. These methods will be applied to a wide range of structural motifs in nucleic acids. The proposed research should provide a better understanding of basic principles of RNA folding.
9984129 Bevilacqua核酸(NA)是由四个结构单元--A、C、G和T(或U)碱基--组成的聚合物,它们以线性方式连接,就像串珠一样。 天然存在的核酸可以根据单个氧原子或甲基(CH 3)的细微差异正式分为两种类型,DNA和RNA。 对生命至关重要的两个基本功能是储存决定个体身份的遗传信息,以及增加对生命至关重要的化学反应的速率和特异性,例如新陈代谢和复制。 在细胞中,DNA用于存储遗传信息,而蛋白质则作为酶来加速反应速率。 引人注目的是,RNA既可以存储遗传信息,如某些病毒如导致艾滋病的HIV-1所证明的那样,又可以作为一种酶,RNA酶被称为“核酶”。 这些特性使RNA参与了各种各样的生物过程和疾病,使RNA的结构和功能成为人们关注的焦点。 此外,RNA还被认为是生命前化学和生命起源中的重要分子,因为RNA有可能解决酶或遗传信息中的“鸡和蛋的问题”。RNA的功能特性源于广泛的复杂三维结构。 该提案中描述的研究的主要目标是了解RNA如何折叠成这些结构。 RNA的序列,或四个碱基出现的顺序,可以很容易地获得。 例如,已经完成了大约25种不同生物体的基因组测序,预计将在今后五年内完成对具有30亿个DNA碱基的人类基因组的测序。 为了理解这些RNA的功能,结构模型是必不可少的,而预测结构的计算机方法对于跟上测序项目的步伐至关重要。 PI的实验室正致力于使用一种新的方法来获得计算机预测的规则。 研究人员正在开发一种组合方法,其中包含多达100亿个不同序列的分子集合被制备,然后根据热力学稳定性或结构对热变性的抵抗力在单个实验中分离。 在含有温度梯度(TGGE)的凝胶电泳装置上进行分离。 将通过克隆和测序分离和鉴定异常稳定和不稳定的序列,并通过对所选序列的进一步物理表征获得结构预测的规则。 这些方法将应用于核酸中的广泛的结构基序。 拟议的研究应该能更好地理解RNA折叠的基本原理。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Philip Bevilacqua其他文献
Philip Bevilacqua的其他文献
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{{ truncateString('Philip Bevilacqua', 18)}}的其他基金
Collaborative Research: RESEARCH-PGR: Genetic and environmentally-induced functional variation in the rice RNA structurome
合作研究:RESEARCH-PGR:遗传和环境诱导的水稻 RNA 结构功能变异
- 批准号:
2122357 - 财政年份:2021
- 资助金额:
$ 49.55万 - 项目类别:
Standard Grant
The In Vivo Rice RNA Structurome in Abiotic Stress Sensing and Response
非生物胁迫感知和响应中的体内水稻 RNA 结构组
- 批准号:
1339282 - 财政年份:2014
- 资助金额:
$ 49.55万 - 项目类别:
Continuing Grant
Conference: 16th Annual Rustbelt RNA Meeting to be held October 17-18, 2014 at the Marriott City Center Downtown in Pittsburgh, PA
会议:第 16 届 Rustbelt RNA 年度会议将于 2014 年 10 月 17 日至 18 日在宾夕法尼亚州匹兹堡市中心万豪酒店举行
- 批准号:
1419355 - 财政年份:2014
- 资助金额:
$ 49.55万 - 项目类别:
Standard Grant
Mechanistic studies of proton transfer in ribozyme self-cleavage
核酶自裂解中质子转移的机理研究
- 批准号:
1213667 - 财政年份:2012
- 资助金额:
$ 49.55万 - 项目类别:
Standard Grant
MRI: Acquisition of High-Throughput Calorimeters for Ligand-Biopolymer Discovery and Characterization
MRI:获取高通量热量计用于配体生物聚合物的发现和表征
- 批准号:
0922974 - 财政年份:2009
- 资助金额:
$ 49.55万 - 项目类别:
Standard Grant
The Influence of Secondary Structure on the Folding and Catalysis of Functional RNAs
二级结构对功能RNA折叠和催化的影响
- 批准号:
0527102 - 财政年份:2005
- 资助金额:
$ 49.55万 - 项目类别:
Continuing Grant
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