PhD position (Genome Stability & DNA Repair): Cellular responses to DNA damage and replication stress • Institute of Molecular Biology (IMB) • Mainz

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PhD position (Genome Stability & DNA Repair): Cellular responses to DNA damage and replication stress • Institute of Molecular Biology (IMB) • Mainz

Open Positions1
Time Span01 Mar 2019 for 3 years
Application Deadline12 Nov 2018
Financingyes
Type of PositionPhD – Doctoral Programme
Field of ResearchMathematics / Natural Sciences
SubjectsBiology
DescriptionIn the field of “Cellular responses to DNA damage and replication stress’’ the research group of Dr Petra Beli offers the following PhD project:
Analyses of the DNA replication stress response using mass spectrometry-based proteomics

Scientific Background:
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.

PhD project:
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. The PhD candidate 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, wild type cells and cells lacking relevant protein kinases and ubiquitin ligases will be used to examine the impact of phosphorylation and ubiquitylation on protein dynamics on damaged chromatin. 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, the PhD candidate 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.

We offer
• The possibility to work on a cutting-edge project using state-of-the-art technology in a highly motivated research team
• A stimulating, diverse and international research environment
• Advanced training opportunities in scientific, technical and transferrable skills 
• Fully funded positions

Starting date: 1 March 2019 or later
Duration of stipend/salary: 3 years, with the possibility of extension
Deadline for registration (exclusively online via web form): 12 November 2018
For further questions and contact information, please check our website:
www.imb.de/PhD 

Please apply exclusively via our online form at: http://imb.de/ipp-reginfos

RequirementsRequired qualifications
• Master or Diploma
• Motivation to solve complex scientific problems
• Good communication skills in English

Further requirement:
• Two letters of reference
Working LanguageEnglish
Language of DissertationEnglish
Required DocumentsCVReports, certificatesTranscriptsLetter of MotivationOthers : 2 Letters of Reference
More Informationhttps://www.imb.de/students-postdocs/international-phd-programme/apply-to-ipp/projects-offered/petra-beli/

Contact

Institute of Molecular Biology (IMB) • International PhD Programme “Gene Regulation, Epigenetics & Genome Stability” 
PhD Elmar Uherek
Ackermannweg 4
55128 Mainz 

Mail: phd@imb.de
Phone: 0049 6131 3921454
http://www.imb.de/PhD

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