Fanconi Anaemia (FA) is a rare disease caused by genetic defects in DNA repair. FA is the most common cause of inherited bone marrow failure, these patients also frequently develop myelodysplasia (MDS) and have an extreme predisposition to acute myeloid leukaemia (AML) - two pathologies characterised by loss bone marrow genome stability leading to abnormal karyotypes.

In this proposal we aim to assess karyotypic abnormalities at single nucleotide resolution. We will build upon our previous findings in mice, that have shown spontaneous genome instability in the bone marrow compartment. Using novel single cell sequencing techniques we will determine the frequency and also the pattern of chromosomal aberrations in the blood and bone marrow. We will combine this new technique with mouse genetics to probe the mechanics of how these chromosome breaks arise in this devastating human disease. We will use clinical samples from human FA patients to potentially develop novel biomarkers to determine the degree of genome instability but also to detect the emergence of recurrent aberrations. This project will shed light on the origins of genomic during haematopoiesis, and will guide clinicians in the treatments of bone marrow failure and MDS/AML. Put together, the project will combine molecular biology, mouse genetics, single cell sequencing and other NGS techniques and analysis of patient material to shed light on the origins of genomic instability.

We are looking for an outstanding PhD candidate (MSc or equivalent qualification) with a strong background in molecular biology, genetics and/or bioinformatics. The candidate should be passionate about biology, curious 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 with the possibility of an extension after positive evaluation.

Depending on education and experience the minimum salary is € 2.451,- and the maximum salary is € 3.247,- 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.

Hubrecht Institute

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).

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.