PhD student – 38 hours p/w

Genome maintenance pathways are crucial to preventing genetic diseases such as cancer. Major progress has been made in our understanding how DNA damage is repaired. Yet, even in the absence of damage, DNA itself can adopt unusual conformations that threaten the integrity of the genome. These non-B form DNA structures, including hairpins, cruciforms, and G-quadruplexes, can obstruct DNA replication forks and trigger mutations if left unresolved. While we recently made significant progress in understanding how G-quadruplexes are resolved, the mechanisms that govern the resolution of other non-B form structures remain largely unknown. Importantly, these structures are particularly common in repetitive DNA regions, whose fragility is linked to neurodegenerative disorders. In this project, you will investigate new molecular pathways that resolve these alternative DNA structures. This will provide insights into their potential roles in the onset of human disease and genome stability in general.

We will use the powerful Xenopus egg extract system to mimic the resolution of key non-B form DNA structures under near-physiological conditions, enabling precise dissection of their unfolding mechanisms during DNA replication. By integrating defined DNA templates, biochemical assays, and mass spectrometry, we will uncover how these structures are detected and processed, and what consequences they impose on genome stability.

This is an opportunity to join a team at the forefront of genome maintenance research and contribute to discoveries with potential impact on our understanding of neurological disorders and cancer. Our institute offers a highly collaborative, ambitious, and supportive research environment with access to excellent facilities and expertise.

Requirements

We seek a highly motivated and independent scientist with an MSc degree, a strong collaborative spirit, and a passion for working in an international research environment. A background in molecular biology is required, and experience in protein biochemistry is an advantage.

Final application date is October 31st 2025, suitable candidates might be invited prior to this date. For additional information please contact prof. dr. Puck Knipscheer (p.knipscheer@hubrecht.eu) or visit www.hubrecht.eu.

About the 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).

Terms of employment
Depending on education and experience the minimum salary is € 3.059,- and the maximum salary is € 3.881,- gross per month for a full-time appointment (scale P cao Nederlandse Universiteiten/KNAW). This is exclusive of 8% vacation allowance, 8.3% year-end bonus, travel allowance, internet allowance, home working allowance and pension accrual with ABP.

The KNAW offers its staff an excellent package of secondary benefits. A package that meets the different needs of employees depending on their stage of life, lifestyle or career ambitions. For example, by working an extra two hours a week, it is possible to increase the number of days off from 29 to 41 days a year (with full-time employment).

For a complete overview of the terms of employment, please refer to the web page: werken bij de KNAW.

Applying for a Certificate of Good Conduct can be part of the employment procedure.

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.