PhD Position (Genome Stability & DNA Repair): Systems Biology of the Stress Response

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 “Systems Biology of the Stress Response”, the research group of Prof. Alexander Löwer, located at the Technical University of Darmstadt, offers the following PhD project:

Quantitative time-resolved analysis of DSB repair in individual living cells

As DNA double-strand breaks (DSBs) pose a major threat to genomic integrity, cells evolved sophisticated pathways to repair these lesions. Which pathway is used to repair a given break depends on the nature of the lesion, the genomic context and the state of the cell cycle. However, cell cycle regulation is a dynamic process and cells often progress through the cell cycle despite the presence of DNA damage due to incomplete or compromised checkpoints. Therefore, the availability and suitability of repair pathways may change during the cellular response to DSBs and cells have to integrate DSB repair with other processes such as replication and chromosome segregation. For example, homology dependent repair (HDR) becomes available after the transition from G1 to S phase and it has been shown that error-prone recombination events take place at breaks induced during G1 phase. During the transition from G2 to M, cells need to handle breaks that are in the process of HDR and ensure that they are repaired in the following G1 phase. While we have a good understanding how repair pathway choice is regulated in each stage of the cell cycle at a given time, little is known about how DNA repair adjusts to dynamic process during cell cycle transitions. One of the main obstacles in gaining deeper insights into this process is the asynchrony and infrequence of such transitions, preventing application of most common approach from biochemistry and molecular biology.

As the PhD student in the Löwer group, you will investigate the repair of endogenous and induced DSBs during cell cycle progression using quantitative time-resolved analysis of individual living cells. To this end, you will combine live-cell imaging of fluorescent reporter cell lines with computational image processing and statistical analysis. You will initially follow DSBs using 53BP1 and MDC1 – based reporters and determine cell cycle progression using in-silico synchronization and cell cycle markers. You will combine live-cell imaging with immunofluorescence staining of proteins involved in non-homologous end joining and HDR at different end-points to determine for each break the repair pathway usage after phase transitions. To follow DSB and pathway usage over time in the same living cell, you will establish reporters for indicative HDR components by using Cas9-mediated genome engineering. To gain mechanistic insights, you will perform pharmacologically or genetically perturbations of repair and signaling pathways and monitor ensuing changes in DNA repair in living cells. Finally, you will use the resulting quantitative data to establish mathematical models of the interplay between DSB repair and cell cycle progression and validate these experimentally.

Qualification profile

Required qualifications
  • Master or equivalent
  • Motivation to work at the forefront of science
  • Interactive personality & good command of English
  • 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-AL

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