HETERONUCLEAR MULTI-DIMENSIONAL NMR STUDIES OF RNA

这项奖励将提供工资支持，这将显著减少 应聘者的教学负担，因此将允许更多的努力 致力于RNA的溶液结构研究。 具体地说，该奖项将把候选人的教学负担减半。 从正常的每年两个(3个学分)课程改为一个课程。这 减轻教学负担意味着考生可以充分利用 科罗拉多大学博尔德分校独特的研究机会 提供了对RNA结构的研究。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的 生物学。这位候选人在1988年搬到了博尔德，以利用这一点 环境，并从那时起在核能方面建立了一项研究努力 核磁共振对核糖核酸的结构研究。这项工作是对 候选人之前在DNA核磁共振研究领域的研究 和抗菌肽。投入研究的更多时间 通过这种教学负荷的减少，将允许核磁共振的下一阶段 核糖核酸的结构研究将加速进行。这一阶段 将涉及异核多维核磁共振实验的应用 用于生物活性RNA的结构测定。这个 异核核磁共振实验是目前革命性的解决方案 蛋白质的结构测定，但这些技术还没有实现 应用于RNA的研究。将研究的RNAs包括：i)两个 RNA酶，自切割的锤头和发夹RNA结构域，都是 它们在体内具有作为位点特异性RNA的潜在重要应用 内切酶，可以被设计成特异性地切割目标mRNA或 RNA病毒的基因组，如HIV；ii)酵母tRNA(Phe)系统，它 将作为开发身份识别技术的模型系统 RNA中的三级相互作用；以及iii)几个RNA结构基序 包括一组异常稳定的自然产生的RNA发夹 含有四核苷酸环的生物。由提供的结构信息 核磁共振实验将与额外的生物和 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.