Last application date Jul 31, 2025 00:00
Department GE31 - Department of Biomolecular Medicine
Contract Limited duration
Degree Master's degree in Medicine, Pharmaceutical Sciences, Veterinary Medicine, Biomedical Sciences or equivalent. Final year students are encouraged to also apply.
Occupancy rate 100%
Vacancy type Research staff
Job description
The Ectopic Mineralization Research Group (EMRg) within the Center for Medical Genetics at Ghent University Hospital has a vacancy available for a PhD fellowship on the following research project; ”Exploiting the genomic architecture of ectopic calcification: from variants to genome-guided therapy, using pseudoxanthoma elasticum as a model."
Mineralization of soft tissues such as skin or blood vessels leads to destruction of the affected tissue and hence important morbidity and mortality. It is a feature in common disorders such as chronic kidney disease, atherosclerosis and diabetes mellitus. A more extreme presentation of soft tissue mineralization can be seen in genetic disorders, of which pseudoxanthoma elasticum (PXE) is considered a hallmark disease.
PXE is an autosomal recessive connective tissue disorder mainly characterized by calcification and fragmentation of the elastic fibers in the extracellular matrix of the skin, eyes and cardiovascular system. The disease is most commonly caused by mutations in the ABCC6 gene. This results in progressive skin lesions, retinal bleeding leading to blindness and accelerated atherosclerosis with a high cardiovascular risk. Currently, the management of PXE focusses on symptom control and prevention as no treatment is available. This research project aims to evaluate the efficacy of genome-guided therapy in ectopic calcification, common in acquired and heritable disorders, by using PXE as a model.
Indeed, PXE presents many of the molecular and treatment challenges which are common in ectopic calcification: i) many of the variants found in the ABCC6 gene are variants of unknown significance for which no experimental validation is available; ii) the genotype remains unknown or incomplete in approximately 20% of PXE patients with a clinical and histological diagnosis; and iii) there are no causative treatments for PXE to date, despite considerable morbidity and mortality. By focusing on correcting the cause of disease rather than the symptoms, genome-guided therapy provides a promising line of treatment for PXE and related EC disorders. First, we will optimize the detection of pathogenic variants that are missed by current screening approaches. We will focus on non-coding ABCC6 variants and variants in novel disease genes, using whole genome sequencing (WGS). Next, validated biochemical assays will be used to evaluate the effect on protein function of non-coding and coding ABCC6 variants. Once pathogenicity is established, we will use CRISPR-nuclease based strategies to correct the genetic defect by increasing endogenous ENPP1 expression for ABCC6 missense or nonsense variants and correcting splicing defects by non-coding variants. This project will lead to major advances in our knowledge on the molecular variability of PXE patients and will contribute to better diagnosis and treatment perspectives.
This project is carried out in collaboration with the University of Münster (Germany) and the Semmelweis University (Hungary) within an international network to unravel and efficiently treat the causes of ectopic mineralization in hereditary and acquired diseases. In this context, the EMRg is the coordinator of this international network on ectopic calcification (INTEC - International Network on Ectopic Calcification - www.itnintec.com).
Job profile
- You hold or will hold a Master's degree in Medicine, Pharmaceutical Sciences, Veterinary Medicine, Biomedical Sciences or equivalent. Students in their final year are also eligible to apply.
- You have a strong interest in research and are highly motivated to complete a PhD within a 4-year period.
- You have excellent study results.
- You have a very good knowledge of Dutch and English, both written and spoken.
- You can work autonomously as well as in a team.
- You are stress resistant and flexible.
- You have strong organizational skills.
- Candidates must be in possession or be willing to obtain Certificate in Test Animal Science.
WHAT WE CAN OFFER YOU
- We offer a full-time position as a doctoral fellow, consisting of an initial period of 12 months, which - after a positive evaluation, will be extended to a total maximum of 48 months.
- Your contract will start on September 1, 2025 at the earliest.
- The fellowship amount is 100% of the net salary of an AAP member in equal family circumstances. The individual fellowship amount is determined by Team Personnel Administration based on family status and seniority. A grant that meets the conditions and criteria of the regulations for doctoral fellowships is considered free of personal income tax. Click here for more information about our salary scales
- All Ghent University staff members enjoy a number of benefits, such as a wide range of training and education opportunities, 36 days of holiday leave (on an annual basis for a full-time job) supplemented by annual fixed bridge days, bicycle allowance and eco vouchers. Click here for a complete overview of all the staff benefits.
How to apply
If you are interested, please send the necessary documents to prof. dr. Olivier Vanakker ([email protected]) and dr. Karolien Aelbrecht ([email protected]) by July 31, 2025, 11:59 pm.
Necessary documents (in one pdf) :
- CV
- Short motivation (1 page)
- A copy of your study results
For more information, please contact prof. dr. Olivier Vanakker ([email protected]) by e-mail.
