PhD position (RNA Biology): Function and Interactions of the RQT Complex and RNA Repair Enzyme ALKBH3 • Institute of Molecular Biology, Johannes Gutenberg University Mainz and its University Medical Center • Mainz

• PhD – Doctoral Programme

• Mathematics / Natural Sciences

The programme is coordinated by the Institute of Molecular Biology (IMB) —a modern research centre located on the bustling campus of Mainz University in Germany. With a population of 210,000, of which about 40,000 are students, the city of Mainz is charming and open-minded and is within easy reach of cosmopolitan Frankfurt, the Rhine valley region with its castles, vineyards, and nature reserves, and the equally picturesque cities of Wiesbaden and Heidelberg. With Frankfurt airport – one of the largest airports in mainland Europe – only 20 minutes away, countless European and overseas destinations are within easy reach.

Activities and responsibilities:

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

Function and Interactions of the RQT Complex and RNA Repair Enzyme ALKBH3

To protect cells from dysfunctional and toxic, disease-causing proteins formed by aberrant translation, eukaryotic co-translational quality control pathways detect translation defects and remove aberrant protein products, together with associated faulty mRNA blueprints and sometimes faulty ribosomal components. In the model eukaryote, budding yeast, the important quality control trigger factor Hel2 acts together with the ribosome-associated quality control trigger (RQT) complex to sense ribosome collisions and mark collided ribosomes for downstream processing.
We have characterized interactions of Hel2 with RNA using the UV crosslinking and analysis of cDNA (CRAC) technique (Winz et al., 2019). In mammals, the ASC-1 complex has recently been described as an equivalent of the yeast RQT complex, but is also involved in DNA damage repair, where it recruits the demethylase ALKBH3 to sites of DNA damage.

PhD Project:

In the first part of this project, using CRAC and selective ribosome profiling, we will test how different members of the RQT complex interact with RNA and ribosomes, and how they cooperate with each other and with Hel2 in triggering quality control in yeast.

In the second part of this project, we will explore whether the ASC-1 complex, together with the mammalian ortholog of Hel2 (ZNF598) can also recruit ALKBH3 to modified or damaged mRNA upon ribosome stalling. This could represent a repair strategy, as an alternative to the degradation usually triggered by ZNF598. In vitro and in vivo we will test the effect of mRNA modifications and damage on translation and on recruitment of the human ASC-1 complex and ALKBH3. Employing sequencing-based analyses of RNA modifications, we will test if ALKBH3 actively removes RNA modification at such sites.

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 140 PhD students from 40 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!

We seek enthusiastic applicants with a special interest in the following topics:
• Ageing & Disease
• Bioinformatics & Computational Biology
• DNA Repair & Genome Stability
• Epigenetics & Nuclear Dynamics
• Gene Regulation & Evolution
• RNA Biology

Further requirements:
• 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 www.imb.de/phd

The deadline for registration is 27 November 2020. Interviews will take place on 25-27 January 2021 or online at a similar time depending on the pandemic situation.

Starting date: 1 March 2021 – 30 September 2021

• English

• English

• CV
• Reports, certificates
• Transcripts
• Letter of Motivation
• Others : 2 Letters of Reference