We are looking for a postdoctoral researcher to contribute to a groundbreaking project addressing a critical challenge in cancer prevention: understanding the initial steps of breast cancer development in BRCA1 mutation carriers. This role involves working at the forefront of human tissue biology, single-cell genomics, spatial imaging, and functional mouse modeling to map the genetic and phenotypic landscape of BRCA1-deficient precancerous cells from prophylactic mastectomy specimens. You will translate these findings into functionally validated driver candidates, linking your research directly to clinical cancer interception.

About the Company

The Jonkers laboratory at the Netherlands Cancer Institute is renowned for its functional breast cancer modeling platform, integrating germline genetics, intraductal somatic engineering, and quantitative in vivo imaging. We are currently applying this platform to investigate the biology of BRCA1-associated precancer and are seeking an exceptional postdoctoral researcher to lead this effort.

The Role

You will utilize a novel mouse model that combines germline heterozygous Brca1 deficiency with a dual-color fluorescent reporter, allowing real-time tracking of cells undergoing Cre-mediated loss of heterozygosity (LOH). Preliminary data indicates that Brca1 LOH cells are actively cleared from the ductal epithelium in vivo, a process that can be rescued by Trp53 loss, providing a quantitative benchmark for assessing candidate perturbations.

Candidate driver genes will be somatically introduced at low frequency in mice, mimicking the early mutation occurrence in BRCA1 mutation carriers. This will be achieved through intraductal delivery of high-titer lentiviruses encoding Cre alongside cDNAs for overexpression or CRISPR guides for loss-of-function. Candidate genes will be prioritized based on human precancer genomic data and in vitro functional genetic screens. The outcomes will be assessed through whole-mount imaging of entire mammary glands at single-cell resolution, enabling the quantification of clone persistence, expansion, and progression to early lesion formation throughout the gland. Additionally, you will explore how immune-epithelial interactions in precancerous ducts influence clonal persistence and tumorigenesis.

Requirements

• PhD in Cancer Biology, Cell Biology, Molecular Biology, or a closely related field
• Strong analytical and quantitative skills with a genuine interest in mechanistic in vivo research
• Experience with mouse models, lentiviral systems, CRISPR, or mammary gland biology is advantageous
• Ability to critically evaluate experimental setups and effectively address scientific questions
• Interest in interdisciplinary research and integrating insights from various fields
• Comfort with the iterative nature of in vivo research

What We Offer

• A three-year contract for 36 hours per week
• A gross monthly salary between €3,903 and €5,503, depending on experience
• 144 holiday hours and 57 hours of Personal Life Budget for full-time employment
• Annual holiday pay of 8.33% and a fixed end-of-year bonus of 8.33%
• Travel allowance of €0.23 per km and free parking at the institute
• Opportunities for continuous learning through the AVL Academy
• Access to fitness facilities and an active staff association

Interested candidates are encouraged to apply by clicking the apply button. Please include your CV, a brief cover letter detailing your interest in the project and what you can contribute, along with the names of two references. Ensure that reference information is included with your CV or cover letter, as separate submissions are not possible.

For further inquiries about the position, please reach out to Jos Jonkers (Senior groupleader) at j.jonkers@nki.nl. For questions regarding the application process, contact Daphne Heemskerk (recruiter) at d.heemskerk@nki.nl. Applications will be reviewed on a rolling basis until the position is filled.