- 36 hours a week
- 4 years
- Date of publication: 19 September 2019
- Deadline: 17 October 2019
- Scale 10A: min € 2422 - max € 3103 gross per month at full employment (excl. vacation bonus and end of year payments)
Job descriptionWe are looking for an enthusiastic and ambitious PhD candidate to study the function of protein glycosylation in brain development. Protein glycosylation is inherently important for normal brain development, as shown by the severe neurodevelopmental problems in children with congenital disorders of glycosylation (CDG). One of the important biological pathways is the production of the monosaccharide sialic acid and patients with defects in this pathway present with epilepsy and intellectual disability.
In this project, you will generate 2D and 3D neuronal model systems from patient-derived induced pluripotent stem cells. Using highly innovative technology for analysis of sugar metabolites and protein glycosylation, you will first map the glycosylation status during normal development. Secondly, patient-derived models will be established and fully characterized by neuronal network assessments with micro-electrode array measurements. Since defects in the sialic acid pathway seems to be amenable to therapeutic intervention, you will trial the established models with sugars, inhibitors and known modulators to identify novel therapeutic strategies. In case of positive results, the outcomes can be translated into patient care by the close collaboration with clinicians within the Expertise Center for Disorders of Glycosylation.
Tasks and responsibilities
- Develop the neuronal model systems using established technology for other gene defects.
- Collaborate with other researchers in the further development of 3D neuronal organoid-like models.
- Collaborate with experts in metabolism and mass spectrometry to elucidate the brain-specific disease mechanisms and test interventions.
- Enthusiasm and ambition to succeed in academic research
- Academic degree (MSc) in one of the molecular life sciences
- Experience with stem cell models, primary cell culture and preferably studies on metabolism
- Background in molecular and cellular neuroscience
- Highly motivated to work in an interdisciplinary environment
- Excellent oral and written communication skills
OrganizationThe project is embedded in the Radboudumc at the interface of the departments of Neurology, Genetics, and the Translational Metabolic Laboratory. Research in these departments is focused on Neurogenetic diseases, aiming for improved diagnosis, better understanding of neuropathophysiology by use of model systems and testing novel therapeutic strategies.
The current position is shared between the Lefeber group on Glycosylation Disorders and the Nadif Kasri group on neuronal model systems. The combined infrastructure is highly innovative including the Radboudumc Technology Center for mass spectrometry (proteomics, glycomics and (sugar)metabolomics) with a wide range of analytical equipment and mass spectrometers, the department of Human Genetics with all modern genomics tools, including next-generation sequencing, CRISPS/Cas9 genome editing, and the Radboudumc stem cell facility. The research of both groups is embedded in the Donders Institute for Medical Neuroscience which harbors a range of top researchers in the field of neurogenetic disease.
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Employment conditionsIntended starting date is January 2020.
Upon commencement of employment we require a certificate of conduct (Verklaring Omtrent het Gedrag, VOG) and there will be, depending on the type of job, a screening based on the provided cv. Radboud university medical center’s HR Department will apply for this certificate on your behalf.
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Comments and contact informationApplication
If you are interested to join our research team, please send your CV, names and addresses of two professional references and a letter describing your motivation, background and ambition to succeed in this project.
All additional information about the vacancy can be obtained from Prof. dr. Dirk J. Lefeber, Glycosylation Disorders in Neurology via +31 (0)24 309 34 87 or from Dr. Nael Nadif Kasri, Molecular neurophysiology and neuronal model group (Dept. Human Genetics) via +31 (0)24 361 42 42. Use the Apply button to submit your application.
Please apply before October 17, 2019.
Recruitment agencies are asked not to respond to this job posting.
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