Thinking of doing your PhD in the Life Sciences? The International PhD Programme (IPP) Mainz is offering talented 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 Helle Ulrich offers the following PhD projects:

The actin cytoskeleton fulfills essential functions in the context of cell migration, cell shape, mechanical signal transduction and many other aspects of cell biology. Actin is a globular protein that can undergo polymerization into so-called filamentous actin (F-actin). The dynamic nature of cytoplasmic actin polymerization and its regulation in the above-mentioned functions is well-understood based on intense research efforts from recent decades. Despite the huge knowledge we acquired on cytoplasmic actin, there is very little evidence for the existence and function of F-actin inside the nucleus. Only recently, based on technological advances, nuclear actin filaments have been observed and characterized - mainly in the context of key genome stability pathways such as DNA repair and the response to DNA replication stress. Our group is interested in nuclear F-actin-regulated processes with a strong focus on the contribution of myosins as actin-based motor proteins.

PhD Project: Investigating the nuclear actin cytoskeleton in DNA repair

Nuclear F-actin has recently been shown to support homology-directed repair (HDR) of DNA double-strand breaks (DSBs). Although myosin I and V were identified to move DSBs along nuclear actin filaments in Drosophila, we currently have no insight into the contributions of myosins to DSB repair in human cells.

Our group recently identified myosin VI as member of the replication protection complex. In addition, we collected preliminary data suggesting a function of myosin VI during DNA repair processes. The aim of this PhD project is to understand and characterize the molecular pathways underlying the functional contribution of the cytoskeletal protein myosin VI addressing the following main questions:

• Does myosin VI cooperate with nuclear F-actin in the resection and mobility steps of the homologous recombination repair pathway?
• How does myosin VI support DNA repair mechanistically?
• Are other myosins and/or cytoskeletal factors/regulators involved?

Furthermore, the PhD student will work on the probes for visualization of cytoskeletal proteins inside the nucleus.

Methods involve cell culture techniques, fluorescence and high-resolution microscopy, gene editing via CRISPR\Cas9, Flow Cytometry (reporter assays) as well as standard molecular biology (cloning, SDS-PAGE, Western Blotting, etc.). In addition, we will perform specialized assays to monitor DNA repair pathway functions.

This project is pending confirmation for third party funding.

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

Qualification profile

Are you an ambitious 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 of more 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 24 October 2024. Interviews will take place at IMB in Mainz on 20-22 January 2025.
Starting date: 1 March 2025 - 1 July 2025