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，我着迷于 RNA依赖的翻译控制机制的多样性和复杂性。在未来，我希望 使我自己的实验室成为研究基因基本机制的杰出中心 以及导致人类疾病的基因表达缺陷。继续我的培训 加州大学伯克利分校的詹妮弗·杜德纳实验室将提供卓越的生物化学技术教育 与翻译相关的RNA-蛋白质相互作用的剖析，以及多样化和激动人心的智力 环境。我还将培养作为一名独立调查员取得成功所需的专业技能 未来，通过无数机会监督具有不同科学优势和 兴趣。 翻译起始是真核基因表达调控的关键环节。为了应对各种 环境侮辱，细胞下调初级(帽子依赖)翻译机制，而 有利于通过可选的启动机制来表达一组选定的基因 将翻译机器招聘到内部核糖体进入位点(IRESS)。人们对此知之甚少 细胞IRES活性的分子基础或这些机制的信息特异性调节。我有过 鉴定了24个在体内外都具有很强活性的酵母细胞IRES元件，创造了一个独特的 结合分子遗传学和生物化学来确定分子基础的机会，以及 IRES依赖基因表达的生理学意义。我的目的是定义IRES的分子功能 细胞IRES RNA序列及其相关的RNA结合蛋白，并最终鉴定 将应激相关信号通路与全局和信息特异性翻译调控联系起来的机制 使用生化、分子遗传学和生物信息学方法的组合。这项工作的成果 将提供对翻译内部启动的机制和调节的详细的分子洞察 通过不同的细胞IRESS，这有望对翻译控制有广泛的影响 真核基因的表达。

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.