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  Untying the knot: Remodelling of G4 structures by the NER machinery- implications in human DNA repair and regulatory pathways

   School of Physics and Astronomy

  ,  Applications accepted all year round  Competition Funded PhD Project (Students Worldwide)

About the Project

Open PhD position on Genome Stability and Biochemistry

Joint PhD scholarship - St Andrews and Bonn-Biology

Untying the knot: Remodelling of G4 structures by the NER machinery- implications in human DNA repair and regulatory pathways

The project will be conducted both in St Andrews (UK) and Bonn (Germany). The student will be supervised by Prof. Carlos Penedo (St Andrews) and Prof. Katrin Paeschke (Bonn).

Project description

Cancer is one of the leading causes of death worldwide. Smoking, alcohol, and/or UV light can lead to mutations within genomic DNA and drive cancer development. In healthy cells, DNA repair mechanisms exist to prevent mutations and disease generation. To better understand the molecular origins of cancer and improve diagnostic and therapeutic applications an enhanced understanding of repair is required.

The observation that DNA can form knotted-like structures revolutionized modern biology, because they can participate in the regulation of many DNA-mediated processes crucial for life. G-quadruplexes (G4s) are specific DNA structures that have raised considerable attention due to their widespread in humans (~700,000 G4 sites) and their implication in cancer development and ageing.

Nucleotide excision repair (NER) is the major repair pathway that is activated upon UV light, environmental mutagens, and certain chemotherapeutic agents. Defects in NER lead to genetic disorders such as Xeroderma Pigmentosum, Cockayne syndrome and cancer. Multiple proteins participate in NER. Among these proteins are XPD and XPB, which are part of the multi-subunit TFIIH complex, and are the focus of the Penedo's lab. In previous work, the Paeschke lab discovered that induction of G4 structures in cells positively influence NER in yeast. These evidences suggest the exciting possibility that G4 formation facilitates NER function. In this project the PhD candidate we will unravel the protein interaction network and its direct implication on NER efficiency at G4s.

The appointed PhD student will integrate the biophysics and biochemical, single-molecule microscopy, and cellular and genomics expertise from both labs to determine the role of G4 structures in NER activation.

It is expected that the student will begin at the University of Bonn. The student may start their degree at any point in the academic year 2023-2024 prior to a final entry date of 27 May 2024 subject to agreement with the supervisory team.

Additional criteria

We are seeking for a highly motivated PhD candidate to work at the interface of molecular biology, biochemistry, and biophysics. Experience in biophysics, biochemistry or microscopy methods is desirable but not required and training will be provided.

Duration of award

Up to 3.5 years. The student will be expected to spend approximately half of the award term at the University of St Andrews and half at the University of Bonn. The successful candidate will be expected to have completed the doctorate degree by the end of the award term. The award term excludes the continuation period and any extension periods.

How to apply

Applicants should submit their full application (motivation letter, CV and names of 2 references), in one pdf, to both co-supervisors by 31st October 2023: Prof. Carlos Penedo (St Andrews) and Prof. Katrin Paeschke (Bonn) at the following email addresses: ; )

Biological Sciences (4) Physics (29)

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