PhD Position (Genome Stability & DNA Repair): Analyses of the DNA replication stress response using mass spectrometry-based proteomics

Thinking of doing your PhD in Molecular Biology? The International PhD Programme (IPP) on “Epigenetics, Gene Regulation & Genome Stability” is offering talented, young scientists the chance to work at the cutting edge of research. The IPP has a community of exceptional scientists working on diverse topics. These range from how organisms age or how our DNA is repaired, to how epigenetics regulates cellular identity or neural memory. This means that no matter where your PhD project takes you, there is always someone to go to for advice or collaborations.
As part of the IPP, you will be given advanced training, covering skills needed for both research and industry. Access to our state-of-the-art Core Facilities and their technical expertise ensures that you are supported no matter how challenging or expansive your project becomes. Importantly, as an IPP student, you are offered a fully funded position with financing until the completion of your thesis. To help you integrate and settle in Mainz, IPP students organise and run a lively social programme with activities to suit everyone.
The IPP is coordinated by the Institute of Molecular Biology (IMB) —a modern research centre located on the bustling campus of Mainz University in Germany. The IPP currently has over 120 energetic students from 30 countries working on innovative research at IMB, Mainz University and its University Medical Centre.
Are you an ambitious, young scientist looking to push back 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!

Activities and responsibilities

In the field of “Cellular responses to DNA damage and replication stress”, the IPP research group of Dr Petra Beli offers the following PhD project:

Analyses of the DNA replication stress response using mass spectrometry-based proteomics

To maintain genome stability, human cells rely on accurate DNA replication in S-phase and chromosome segregation in mitosis. Dynamic assembly and disassembly of protein-protein interactions and their regulation by posttranslational modifications is central for these processes. The genome is exposed to exogenous and endogenous insults that can induce a variety of lesions in different cell cycle stages. DNA lesions present in S-phase of the cell cycle can block the progression of replication forks and thus lead to replication stress. Replication stress refers to slow down or stalling of replication forks that can occur as consequence of exogenous DNA damage such as chemotherapeutic drugs as well as in response to endogenous sources: For instance, the progression of replication forks is problematic at chromosomal fragile sites, telomeres, repetitive sequences and DNA–RNA hybrids (e.g. R loops). Prolonged replication stress can also lead to the formation of highly cytotoxic DNA double strand breaks. Therefore, the mechanisms that protect stalled replication forks and repair replication stress-associated double strand breaks are essential for maintaining genome stability and preventing the development of diseases such as cancer.
The recruitment of DNA repair factors to sites of DNA lesions and replication stress is a dynamic process that is tightly regulated by posttranslational modifications of proteins, in particular phosphorylation and ubiquitylation. The full scope of proteins operating at different types of DNA lesions, in particular sites of replication stress, and the mechanisms that lead to the regulated recruitment of factors to these lesions are not understood.
As a PhD student in the Beli lab you will employ recently developed proximity tagging approaches based on engineered ascorbate peroxidase (APEX) or biotin ligase (BioID) combined with SILAC-based quantitative mass spectrometry to investigate the recruitment of proteins and the formation of protein complexes at sites of replication stress and replication stress-associated double strand DNA breaks. These studies will be performed after replication stress-induced by endogenous sources such as R-loops and exogenous sources such as chemotherapeutic drug hydroxyurea. Furthermore, you will use wild type cells and cells lacking relevant protein kinases and ubiquitin ligases to examine the impact of phosphorylation and ubiquitylation on protein dynamics on damaged chromatin. Your proteomics experiments will be complemented by cell biological methods such as high throughput microscopy, flow cytometry, functional DNA repair assays and next generation sequencing. In addition, you will have the opportunity to collaborate with leading researchers in the field having complementary expertise in order to execute parts of the project. This projects aims to obtain a first systematic view of protein components and mechanisms that operate in the replication stress response and thus confer essential roles in genome stability maintenance.

Qualification profile

Required qualifications
  • Master or equivalent
  • Motivation to work at the forefront of science
  • Interactive personality & good command of English
Further requirement:
  • 2 letters of reference

Benefits

We offer
  • The possibility to work on exciting, multidisciplinary projects using state-of-the-art technology in highly motivated research teams
  • To be part of a lively and international community of about 120 IPP students from 30 countries
  • Numerous opportunities for advanced professional training in scientific knowledge, techniques and professional skills
  • Fully funded positions until completion of thesis
Starting date: 1 August 2019 – 1 February 2020
Duration of stipend/salary: 3 years, with the possibility of extension

Deadline for registration (exclusively online via web form): 22 May 2019

Send application to

Please find all relevant information on the application process at: http://imb.de/ipp-reginfos

Bitte beziehen Sie sich bei Ihrer Bewerbung auf jobvector und geben Sie die folgende Referenznummer an: JV-C17-PeBe

Über Institute of Molecular Biology gGmbH

Our International PhD Programme on the “Gene Regulation, Epigenetics and DNA Damage Response” gives talented and enthusiastic students the opportunity to undertake PhD research at the cutting edge of modern biology. Our groups cover a broad range of expertise and include leading biochemists, geneticists, cell and developmental biologists who study the molecular mechanisms of embryonic...
Mehr über Institute of Molecular Biology gGmbH