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

• Applicant: Marco Nousch, Ph.D.
• Subject Area: Developmental Biology
• Term: from 2018 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 407066676

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.

• DFG Programme: Research Grants