HETERONUCLEAR MULTI-DIMENSIONAL NMR STUDIES OF RNA

该奖项将提供工资支持，这将大大减少 学生的教学负担，因此将允许更多的努力， 致力于RNA的溶液结构研究。 具体来说，该奖项将把候选人的教学负担减少一半 从每年正常的两门（3学分）课程到一门课程。 这 减轻教学负担意味着考生可以充分利用 独特的研究机会，科罗拉多大学博尔德分校 研究RNA结构。 博尔德有八个研究小组 在RNA生物化学和分子生物学领域非常活跃 生物学 这位候选人在1988年搬到博尔德，以利用这一点 环境，并从那时起建立了核研究工作， RNA的核磁共振（NMR）结构研究。 这项工作补充了 候选人在DNA核磁共振研究领域的先前研究 和抗微生物肽。 用于研究的时间增加了 通过这种教学负担的减少将允许下一阶段的核磁共振 RNA的结构研究将加速进行。 这个阶段 将涉及应用异相多维NMR实验 生物活性RNA的结构测定。 的 杂波NMR实验是目前革命性的解决方案 蛋白质的结构测定，但这些技术还没有 应用于RNA的研究。 将被研究的RNA包括：i）两个 RNA酶，自切割锤头状和发夹状RNA结构域， 其作为位点特异性RNA在体内具有潜在的重要应用 可以设计为特异性切割靶mRNA的核酸内切酶，或 RNA病毒如HIV的基因组; ii）酵母tRNA（Phe）系统， 将作为开发识别技术的模型系统 RNA中的三级相互作用;和iii）几种RNA结构基序 包括一组异常稳定和自然发生的RNA发夹 含有四核苷酸环。 所提供的结构性信息 核磁共振实验将与其他生物和 生物化学数据，以改善结构-活性关系， RNA。

This award will provide salary support that will significantly reduce the teaching load of the candidate and therefore will allow much more effort to be devoted to research on solution structural studies of RNAs. Specifically, the award will cut the teaching load of the candidate in half from the normal two (3 credit) courses per year to a single course. This reduced teaching load means that the candidate can take full advantage of unique research opportunities that the University of Colorado at Boulder offers for studies of RNA structure. Boulder has eight research groups that are extremely active in the areas of RNA biochemistry and molecular biology. The candidate moved to Boulder in 1988 to take advantage of this environment and since that time has set up a research effort in nuclear magnetic resonance (NMR) structural studies of RNA. This work complements the previous research by the candidate in the areas of NMR studies of DNA and antimicrobial peptides. The increased time that be devoted to research by this reduction of teaching load will allow the next phase of the NMR structural studies of RNA to proceed at an accelerated pace. This phase will involve application of heteronuclear multi-dimensional NMR experiments to the structure determination of biologically active RNAs. The heteronuclear NMR experiments are presently revolutionizing solution structure determinations of proteins, but these techniques have yet to be applied to studies of RNAs. The RNAs that will be studied include: i) two RNA enzymes, the self-cleaving hammerhead and hairpin RNA domains, both of which have potentially important in vivo applications as site-specific RNA endonucleases which can be designed to specifically cleave a target mRNA or the genome of an RNA virus such as HIV; ii) a yeast tRNA(Phe) system that will serve as a model system for developing techniques for identification of tertiary interactions in RNAs; and iii) several RNA structural motifs including a set of unusually stable and naturally occurring RNA hairpins that contain tetranucleotide loops. The structural information provided by the NMR experiments will be combined with additional biological and biochemical data in order to improve structure-activity relationships for RNAs.