Description of the project:

DNA carries the instructions of life, but is also under constant attack. The resulting damage, if not repaired, leads to mutation and disease. The recent genome sequencing revolution has revealed unexpected diversity in mutational patterns. One pattern in particular is intriguing as it behaves as a molecular 'clock': the number of mutations increases over time and correlates with age. Although the textbook view of mutagenesis is that cell division is required to convert DNA damage into point mutations, surprisingly, non-dividing cells like neurons also accumulate 'clock' mutations as a function of time, indicating that 'clock' mutations arise without genome replication.

Understanding how cells mutate independently of proliferation is a fundamental question that has been hindered because assays to measure mutation require cell division. Excitingly, we have established a powerful strategy to sensitively detect mutations in single cells, genome-wide. This ERC-funded project will combine this novel sequencing approach with targeted genetic manipulations in cells and mice how cells mutate independently of proliferation. This project will shed light on the molecular mechanism(s) underlying the most common mutational process in humans: 'clock' mutation. We expect that the methods, data, and insights from these studies will impact cancer research and uncover novel sources of DNA damage during ageing.

We are looking for an outstanding PhD candidate (MSc or equivalent qualification) with a strong background in molecular biology, genetics and/or bioinformatics. Experience with neuronal cultures, virus transduction and/or NGS library preparation are desired but not essential. The candidate should be passionate about biology and be motivated to work in an ambitious, multidisciplinary and international research team. The working language in our international team is English, the candidate should therefore have excellent English communication skills and be able to work as part of a team.

Fixed-term contract: 1 year (3 year extension after positive evaluation).

According to "CAO-Nederlandse Universiteiten" (CAO-NU) € 2.541,- in the first year, increasing to € 3.247,- in the fourth year, excluding 8% holiday allowance and an 8.3%
year-end bonus. We offer an extensive package of fringe benefits.

Hubrecht Institute

The Hubrecht Institute is a research institute focusing on developmental and stem cell biology. At the institute, more than 20 research groups perform fundamental and multidisciplinary research, both in healthy systems and disease models. The Hubrecht Institute is a research institute of the Royal Netherlands Academy of Arts and Sciences (KNAW) and is located on the Utrecht Science Park 'De Uithof'. Since 2008, the institute has been affiliated with the University Medical Center Utrecht, advancing the translation of research into clinical practice. The Hubrecht Institute has a partnership with the European Molecular Biology Laboratory (EMBL).

Diversity & Inclusion
The KNAW considers a working environment in which everyone feels welcome and appreciated of great importance. A working environment in which attention is paid to individual quality and where development opportunities are paramount. Together we strive for an inclusive culture in which we embrace differences. We would therefore like to invite candidates who want to contribute to this through their background and experience. In the event of equal suitability, preference will be given to the candidate who thus enhances diversity within the Academy.