Description of the project:

Cancer is caused by the accumulation of genetic changes. These alterations, known as mutations, are the consequence of mis-repaired DNA damage. Carcinogens like UV light or cigarette smoke lead to cancer by damaging DNA and inducing mutations. However, the recent explosion in genome sequencing has revealed a much greater diversity of mutation patterns than expected. Many of these mutations have unknown origins, however they are likely driven by currently uncharacterised endogenous threats.

This NWO-funded project aims to shed light on the nature of some of these endogenous insults, more specifically, bulky DNA lesions which are normally removed by Nucleotide Excision Repair (NER) and likely underlie mutation patterns of unknown origin. NER is normally studied in the context of DNA damage caused by UV light, but the nature of the endogenous legions repaired by this pathway is still largely unknown. To shed light into this, this project will leverage a novel single-cell sequencing approach to define the mutational landscape of tissues that accumulate bulky DNA adducts. Second, we aim to characterise the phenotype of mice that lack DNA repair, to understand the relevance of this endogenous DNA damage for tissue homeostasis and cancer. Finally, in a collaborative effort, we will exploit the latest developments in mass spectrometry to define the nature of lesions and abnormal bases in DNA. By combining genomics, mouse genetics and cutting-edge 'DNA adductomics', we hope to gain insight into the nature of endogenous DNA damage. These findings will shed light on the mechanisms that underlie mutations found in cancer, and this knowledge may be exploited to limit the exposure to these endogenous insults or develop new therapies.

We are looking for outstanding and highly-motivated postdoctoral candidates with mastery of molecular biology, biochemistry and/or genomics. In particular, we seek a candidate with:

• PhD degree in molecular biology, biochemistry, genetics or Life sciences, or related fields.
• a good understanding of molecular- and cell-biology
• ability to work independently, but also as part of a team
• someone with independent attitude to problem-solving who takes initiative
• proficient in molecular biology techniques, experience with NGS library preparation is a plus
• experience with mouse genetics and animal experimentation is desirable but not a must
• the working language in our international teams is English, the candidate should therefore have excellent English communication skills

Fixed-term contract: 1 year with the possibility of an extension after positive evaluation.

We are looking for outstanding and highly-motivated postdoctoral candidates with mastery of molecular biology, biochemistry and/or genomics. In particular, we seek a candidate with:

• PhD degree in molecular biology, biochemistry, genetics or Life sciences, or related fields.
• a good understanding of molecular- and cell-biology
• ability to work independently, but also as part of a team
• someone with independent attitude to problem-solving who takes initiative
• proficient in molecular biology techniques, experience with NGS library preparation is a plus
• experience with mouse genetics and animal experimentation is desirable but not a must
• the working language in our international teams is English, the candidate should therefore have excellent English communication skills

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.

We will not respond to any supplier enquiries based on this job advertisement.