Investigating a ribosome-mRNA competition mechanism as an important regulator for stem cells biology.

核糖体是基因表达途径的重要组成部分，它将mRNA序列翻译成多肽链，再折叠成蛋白质。长期以来，翻译机制一直被认为在调节特定的基因表达程序方面并不重要。然而，核糖体活性的失调可能会对多细胞生物体中特定组织的发育产生毁灭性的后果。有趣的是，在这些受影响的组织中，干细胞的调节似乎经常脱轨，认为组织可能对核糖体的质量或数量有特定的要求和要求。最近，在组织培养系统中进行的一些备受瞩目的研究表明，核糖体本身可以影响几个mRNAs的翻译效率。这证明核糖体是特定转录后调控机制的活跃部分，在发育背景下提出了以下问题：核糖体在由转录后基因表达调控主导的组织和干细胞系统中扮演什么角色，如生殖细胞？为了回答这个复杂的问题，我将在这项提案中研究生殖细胞中核糖体提供的框架。这意味着，我想了解的是，核糖体的活性是否仅限于生殖细胞？MRNAs必须竞争翻译机制吗？这对生殖系干细胞的活动有何影响？在我的工作中，我将利用动物成年性腺中描述得很好的生殖系干细胞系统。通过将最先进的转基因组学与全基因组测序和秀丽线虫强大的遗传工具箱相结合，我旨在了解核糖体活性与基因特异性mRNA调控和干细胞发育之间的关系。

Ribosomes are an important part of the gene expression pathway by translating mRNA sequences into polypeptide chains that fold into proteins. For a long time, the translational machinery has been considered unimportant in regulating specific gene expression programs. However, dysregulation of ribosome activity can have devastating consequences for the development of specific tissues in multi-cellular organisms. Interestingly, often the regulation of stem cells seems to be derailed within such affected tissues, arguing that tissues might have specific requirements and demands toward ribosome quality or quantity. Recently, a number of high-profile studies conducted in tissue culture systems presented evidence that the ribosome itself can influence the translation efficiency of several mRNAs. This argues that ribosomes are an active part of specific post-transcriptional regulatory mechanisms, raising the following question in a developmental context: Which roles have ribosomes in tissues and stem cell systems, which are dominated by post-transcriptional gene expression regulation, such as germ cells? In order to answer this complex question, I will investigate in this proposal the framework that is provided by ribosomes in germ cells. This means, I would like to understand if the activity of ribosomes is limited in germ cells? Do mRNAs have to compete for the translational machinery and how does this influence germline stem cell activities? For my work, I will utilize the well-described germ line stem cell system in an animal’s adult gonad. By combining state-of-the-art transgenomics with whole-genome sequencing and the powerful genetic toolkit of Caenorhabditis elegans, I aim at understanding the connections between ribosome activity to gene-specific mRNA regulation and stem cell development.