PhD position: Molecular Mechanisms in small RNA mediated gene regulation (m/f/d)

Thinking of doing your PhD in the Life Sciences? The International PhD Programme (IPP) Mainz is offering talented, young scientists the chance to work on cutting edge research projects within the open call on “Molecular Mechanisms in Genome Stability & Gene Regulation”. As an IPP PhD student, you will join a community of exceptional scientists working on diverse topics ranging from how organisms age or how our DNA is repaired, to how epigenetics regulates cellular identity or neural memory.

Activities and responsibilities

The research group of René Ketting offers the following PhD project:

Gene regulation by small non-coding RNAs is a deeply conserved mode of gene control. It is used in developmental control of gene expression, but also in the protection of the genome against mobile genetic elements (i.e. transposons). The small RNA molecules function as sequence specific guides for proteins of the Argonaute family, which can repress translation, induce endonucleolytic cleavage or induce heterochromatin upon recognition of transcripts with sequence homology to the small RNA. Hence, the small RNA co-factors are essential players in these pathways as they fully determine the specificity. However, a lot still remains to be discovered about how such small RNAs are made, in particular in the context of genome defense against transposons. Understanding these steps better will increase our understanding of how our genomes discriminate ‘self’ from ‘non-self’, a non-trivial exercise! In addition, past work has shown that the dissection of such pathways has yielded great insights also in the understanding of more basic RNA biology. We are addressing these questions using two model organisms: the nematode C. elegans and the zebrafish. We are looking for people with a strong natural curiosity, perseverance and a high intrinsic motivation. Specific knowledge of the applied techniques is not essential, but a strong basis in molecular biology is required. We offer a highly interactive, stimulating and flexible research environment, with ample opportunities for personal development.

PhD project: Biogenesis and regulation of small RNAs

Which small RNAs are made is of great importance, as the specificity of these pathways depends on it. Recently, we identified a novel nuclease that is a key factor in the generation of a specific type of small RNAs (named piRNAs), and we are further pursuing studies to understand how these piRNAs are made, starting from their transcription, all the way to their binding by a specific member of the Argonaute protein family (the Piwi protein). These are important research questions, as they relate to a much broader problem: how are certain RNA molecules destined to become used as protein-coding messengers, others to be degraded fast, and yet others to be used as (precursors for) non-coding RNAs, such as piRNAs. Resolving these questions will require a much better understanding of different modes of transcription initiation, elongation and termination, and RNA stabilization and de-stabilization, and RNA transport through the nucleus and the rest of the cell. Our recent, unpublished work has made intriguing entries into various of these aspects: we have identified a complex that stabilizes piRNA precursors, and are now studying how this connects to their transcription; we have generated mutants in a nuclear export factor that likely plays a role in piRNA precursor export and we have identified a novel locus that can serve as a source of piRNA precursor transcription.

Depending on expertise and interest, you can join us in studying these aspects, using C. elegans or the zebrafish as model system. The aims of the project can relate to understanding how ‘non-standard’ transcripts can be stabilized for further use, how the nuclear export of such transcripts is taking place, piRNA precursors actually look like, how the loading of small RNAs into an Argonaute protein takes place or how these processes can be regulated by post-translational modifications. Techniques that will be used in this project include microscopy, genetics, CRISPR-Cas genome editing, RNA interference, RNAseq, analysis of sequencing data and protein purification.

If you are interested in this project, please select Ketting (Kett) as your group preference in the IPP application platform.

Qualification profile:

Are you an ambitious, young scientist looking to push the boundaries of research while interacting with colleagues from multiple disciplines and cultures? Then joining the IPP is your opportunity to give your scientific career a flying start!

All you need is:

• Master or equivalent
• Interactive personality & good command of English
• 2 letters of reference

We offer

• Exciting, interdisciplinary projects in a lively international environment, with English as our working language
• Advanced training in scientific techniques and professional skills
• Access to our state-of-the-art Core Facilities and their technical expertise
• Fully funded positions with financing until the completion of your thesis
• A lively community ofmore than 200 PhD students from 44 different countries

For more details on the projects offered and how to apply via our online form, please visit www.imb.de/phd.

The deadline for applications is 17 April 2024. Interviews will take place at IMB in Mainz on 1-3 July 2024.

Starting date: 1 August 2024 – 1 January 2025