Applications are invited for a PhD fellowship/scholarship at Graduate School of Natural Sciences, Aarhus University, Denmark, within the Molecular Biology and Genetics programme. The position is available from February 2025 or later.

Title:
Structural insights into DNA repair in the context of chromatin

Research area and project description:
Different types of DNA damage are detected and repaired by specialized pathways in the DNA damage response (DDR). One particularly hazardous lesion is the DNA double strand break (DSB). If the other copy of the chromosome is available, it can be used as a template to repair the break through a process called homologous recombination (HR). In addition to DSBs caused by external factors, cells can also generate DSBs to resolve other types of DNA damage, such as lesions that block DNA replication. Thus, various DDR pathways converge on a common response, utilizing HR to repair DSBs. Although decades of research have advanced our understanding of HR, we still lack a complete mechanistic understanding of how different protein complexes assemble and work together to detect DSBs and facilitate repair by HR.

A key event in recognizing replication-blocking lesions is the activation of the Fanconi Anemia (FA) pathway, which involves at least 22 FANC proteins. Mutations in the genes encoding these proteins cause FA and increase cancer risk. While we know these proteins are involved in detecting and repairing DNA damage, the precise mechanisms of how they assemble and function are just beginning to emerge.

In this 3-year PhD project, we will employ biochemical reconstitution, cryo-EM, and single-molecule imaging to study:

• The structure of FANC proteins in isolation and in complex with DNA
• The specific role of FANC proteins in the transition from damage recognition to HR
• How FANC proteins interacts with naked DNA, chromatin, and DNA lesions at single-molecule resolution
• The structural basis for FANC proteins enzymatic activity and its connection with HR factors

This project will involve collaborations within the MBG department and with international groups, including Imperial College London. Insights from the single-molecule analysis of FANC proteins interaction with DNA and chromatin will guide biochemical hypotheses and inform the design of substrates for quantitative characterization of these interactions using biophysical analysis.

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Qualifications and specific competences:
Applicants should possess a relevant Master’s degree or have completed at least one year of a Master’s program in molecular biology or protein biochemistry. Additionally, strong English communication skills, both oral and written, are required.

Place of employment and place of work:
The place of employment is Aarhus University, and the place of work is Molecular Biology and Genetics, Universitetsbyen 81, 8000 Aarhus C, Denmark. 

Contacts:
Applicants seeking further information for this project are invited to contact: Professor Ditlev E. Brodersen, deb@mbg.au.dk or Associate Professor Associate Professor, Pablo Alcón, palcon@mbg.au.dk

How to apply:

For information about application requirements and mandatory attachments, please see the Application guide. Please read the Application guide thoroughly before applying.

When ready to apply, go to https://phd.nat.au.dk/for-applicants/apply-here/ (Note, the online application system opens 1 September 2024)

1. Choose November 2024 Call with deadline 1 November 2024 at 23:59 CET.
2. You will be directed to the call and must choose the programme “Molecular Biology and Genetics”.
3. In the boxed named “Study”: In the dropdown menu, please choose: “Structural insights into DNA repair in the context of chromatin (SiiDNA)”

Please note:

• The programme committee may request further information or invite the applicant to attend an interview.
• The project will only be initiated if the graduate school/the faculty grants funding.

At the Faculty of Natural Science at Aarhus University, we strive to support our scientific staff in their career development. We focus on competency development and career clarification and want to make your opportunities transparent. On our website, you can find information on all types of scientific positions, as well as the entry criteria we use when assessing candidates. You can also read more about how we can assist you in your career planning and development.

Aarhus University’s ambition is to be an attractive and inspiring workplace for all and to foster a culture in which each individual has opportunities to thrive, achieve and develop. We view equality and diversity as assets, and we welcome all applicants. All interested candidates are encouraged to apply, regardless of their personal background.