The role of microRNA regulation in the evolution of development

最近发现了一类称为microRNAs(MiRNAs)的小RNA，它通过与转录基因的非翻译区结合来调节基因的表达，从而导致蛋白质的降解和/或抑制形成。这些miRNA究竟是如何发挥作用的还有待发现，因此，人们对miRNA调控对发育和形态发生的重要性知之甚少。与编码基因相比，miRNAs进化得更快，它们也可能更快地获得和失去靶标，因此它们可以在进化过程中提供显着差异的来源。该项目将使用各种分子和计算方法来研究miRNAs在海胆Strongyloctrotus PurPuratus中的功能作用，之所以选择它进行这项研究，是因为它具有非常好的特征的早期发育的基因调控网络。还将通过测试miRNAs是否调控其他棘皮动物的类似基因，特别是在近亲海胆Lytechinus varegatus和远亲海星Asterina mini ata中，来确定这一调控可能是如何进化的，以及这可能会产生什么发育后果。海星和海胆之间基于转录因子的基因调控网络是如何进化的，以及这种进化对它们发育的影响，人们已经知道了很多。预计该项目将揭示miRNA调控如何控制发育，以及它如何在基因调控网络的背景下随着进化时间的推移而变化。几名女研究生和本科生将接受各种实验和计算技术方面的培训。此外，PI和PI实验室的研究生将在Ringold高中开设一个简短的实验室和讲座课程，向这些学生介绍计算生物学和发育生物学的概念。

A class of small RNAs, called microRNAs (miRNAs), has recently been discovered and has been shown to regulate gene expression by binding to the untranslated regions of transcribed genes leading to degradation and/or repression of protein formation. Much remains to be discovered of exactly how these miRNAs function, and consequently very little is known about the importance of miRNA regulation to development and the generation of morphology. MiRNAs evolve rapidly compared to coding genes and they may also acquire and lose targets more rapidly so that they could provide a source of significant variation during evolution. This project will use a variety of molecular and computational approaches to examine the functional role of miRNAs in the sea urchin Strongylocentrotus purpuratus, which was chosen for this study because it has an extremely well characterized gene regulatory network for early development. It will also be determined how this regulation may have evolved, and what developmental consequences this may have, by testing whether miRNAs regulate similar genes in other echinoderms, specifically in the closely related sea urchin Lytechinus variegatus and the distantly related sea star Asterina miniata. A great deal is known of how transcription factor based gene regulatory networks have evolved between the sea star and sea urchins and the consequences of this for their development. It is anticipated that this project will reveal how miRNA regulation can control development and how it changes over evolutionary time in the context of a gene regulatory network. Several women graduate and undergraduate students will be trained in a variety of experimental and computational techniques. Also the PI and graduate students in the PI's lab will run a short lab and lecture course at Ringold High School to introduce these students to the concepts of computational and developmental biology.