PhD position (RNA Biology): Eukaryotic translation quality control

Thinking of doing your PhD in the Life Sciences? The International PhD Programme (IPP) Mainz is offering talented students the chance to work at the cutting edge of research. 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:

In the field of “RNA Biology”, the research group of Marie-Luise Winz offers the following PhD project:

Proteins are central to any living organism. To protect cells from dysfunctional and toxic, disease-causing proteins formed by aberrant translation, eukaryotic translation quality control pathways detect translation defects and remove aberrant protein products, together with associated faulty mRNA blueprints and sometimes faulty ribosomal components. Many of those pathways rely on the recognition of ribosome collisions. Much is still unknown about the molecular mechanisms underlying translation quality control, and how these interact with other cellular machineries and with organismal health and life cycle. These are research objects in my group. Besides reporter systems and polysome profiling techniques, we use sequencing-based methods, most prominently UV crosslinking and analysis of cDNA (CRAC), to study RNA-protein interactions, translation and RNA modification in the context of translation quality control. These techniques provide a unique toolbox to approach our key questions:

1:           Which molecular interactions underlie translation quality control triggering and how are different targets distinguished?

2:           How does translation quality control interact with cellular stress responses, translation regulation and RNA modification?

3:           How does co-translational quality control work in neurons and does it change with ageing and disease?

4:           What is the role of translation quality control for RNA-based and RNA-targeted therapies?

With our RNA-centred research, we want to make fundamental contributions to the understanding of translation quality control and its links to age-related neurodegenerative diseases, to ultimately inform efforts to cure, prevent or delay the onset of such diseases.

PhD project: Option 1: New players in eukaryotic translation quality control

Our group has recently discovered a number of potential new players in translation quality control by collating published information from a range of different databases and studies. We are currently investigating the potential functions of several such players in budding yeast, to define in which processes these proteins are involved and what is their molecular mechanism, using, e.g., CRAC, as well as reporter-based analyses (Müller, Tollervey, and Winz, unpublished; Iyer and Winz, unpublished).

Our current efforts so far only cover a small number of potential candidates. In this project, further candidates will be identified from published data and will be screened by reporter systems, equally in budding yeast. Positively evaluated candidates will be further studied to reveal their role in translation quality control. In addition to evaluating candidates from published screens and databases, to reveal additional candidates, new, targeted screens will be explored, followed by similar screens and evaluations.

PhD project: Option 2: Translation quality control in gene-specific translation inhibition

General inhibitors of bacterial translation play an important role as antibiotics. On the other hand, in human translation, a handful of small molecules have recently been discovered that target biosynthesis of a specific protein by targeting either the mRNA or the nascent peptide. It is now well accepted that many unspecific translation inhibitors can cause ribosome collisions and thereby trigger translation quality control pathways.

In this project, we will investigate which role translation quality control plays in specific translation inhibition in mammalian cells.

If you are interested in one of these projects, please select Winz as your group preference in the IPP application platform.

What we offer:

• Exciting, interdisciplinary projects in a fully 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 of more than 190 PhD students from 44 different countries

Requirements:

Are you an ambitious, young scientist looking to push the boundaries of science while interacting with colleagues from multiple disciplines and cultures? Then 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

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

The deadline for applications is 8 November 2023. Interviews will take place at IMB in Mainz on 22-24 January 2024.

Starting date: 1 March 2024 – 1 August 2024