Mechanisms and Regulation of Yeast Internal Ribosome Entry Sites

我的主要科学兴趣是基因表达的转录后调控。尤其是，我对 依赖RNA的翻译控制机制的多样性和复杂性。未来希望 使我自己的实验室成为研究基因的基本机制的杰出中心 表达，以及导致人类疾病的基因表达缺陷。我的训练是 詹妮弗杜德纳在加州大学伯克利分校的实验室将提供一个杰出的生物化学技术教育， 与翻译相关的RNA-蛋白质相互作用的解剖，以及多样化和刺激的知识分子 环境我还将发展专业技能，我将需要茁壮成长，作为一个独立的调查员， 未来，通过众多的机会，监督学生与不同的科学优势， 利益 翻译起始是真核生物基因表达调控的关键环节。响应于各种 环境损伤，细胞下调翻译的主要（帽依赖性）机制， 有利于通过替代起始机制表达选择的基因组， 将翻译机器募集到内部核糖体进入位点（IRES）。很少有人知道的 细胞IRES活性或这些机制的信息特异性调节的分子基础。我有 鉴定了24个在体外和体内都具有强活性的酵母细胞IRES元件， 有机会将联合收割机分子遗传学和生物化学结合起来，以确定 IRES依赖的基因表达的生理意义。我的目的是确定IRES依赖的基因表达的分子功能。 细胞IRES RNA序列及其相关的RNA结合蛋白，并最终确定 应激相关信号通路与全局和信息特异性翻译调节的联系机制 使用生物化学、分子遗传学和生物信息学方法的组合。这项工作的结果 将提供详细的分子深入了解机制和调控的内部启动翻译 通过不同的细胞IRES，这预计将有广泛的影响，翻译控制的 真核基因表达

My chief scientific interest is post-transcriptional regulation otgene expression. In particular, I am fascinated by the diversity and complexity of RNA-dependent mechanisms of translational control. In the future, I hope to make my own lab an outstanding center for research into the fundamental mechanisms of gene expression, and the defects in gene expression that lead to human diseases. Pursuing my training in Jennifer Doudna's lab at UC Berkeley will provide an outstanding technical education in biochemical dissection of RNA-protein interactions relevant to translation, as well as a diverse and stimulating intellectual environment. I will also develop the professional skills I will need to thrive as an independent investigator in the future, through numerous opportunities to supervise students with diverse scientific strengths and interests. Translation initiation is a crucial point of regulation of eukaryotic gene expression. In response to a variety of environmental insults, cells down-regulate the primary (cap-dependent) mechanism of translation while favoring expression of a select group of genes via alternative initiation mechanisms including direct recruitment of the translation machinery to internal ribosome entry sites (IRESs). Little is known about the molecular basis for cellular IRES activity or for message-specific regulation of these mechanisms. I have identified 24 yeast cellular IRES elements with strong activity both in vitro and in vivo, creating a unique opportunity to combine molecular genetics and biochemistry to determine the molecular basis for, and physiological significance of IRES-dependent gene expression.My aim is to define the molecular functions of cellular IRES RNA sequences and their associated RNA-binding proteins and ultimately, to identify the mechanisms linking stress-related signaling pathways to global and message-specific translational regulation using a combination of biochemical, molecular genetic, and bioinformatic approaches. Results from this work will provide detailed molecular insight into the mechanisms and regulation of internal initiation of translation by diverse cellular IRESs, which is expected to have wide-ranging implications for translational control of eukaryotic gene expression.