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PhD-project Synapse function in human cell models for psychiatric disorders

Research / Academic
Amsterdam
Description of work:

The project exploits induced pluripotent stem cell (iPSC) technology to produce human neurons and create human neuronal networks in vitro. Genome editing is used to alter candidate genes or introduce disease-relevant variation and reporters and patch clamp physiology. You will be part of international research networks and exploit a variety of other analysis tools available here and in our partner labs, also using rodent models. You will be appointed in Amsterdam and work primarily in Amsterdam with regular visits to the other labs. The PhD-students will be trained on site. All the methodology, cell models, equipment, analysis software and viral vectors are available from the start of the projects. 

Several exon variants and single gene CNVs are now firmly associated with schizophrenia, autism and mental retardation. We have previously identified synaptic gene networks where many such risk factors accumulate (Ripke et al. (2013) Nature Genetics 45:p1150-9; Lips et al. (2012) Mol. Psychiatry 17:p996-1006)using two reduced and highly standardized model systems, single human neurons on glia islands and standardized small networks, we aim to systematically analyze the synaptic effects of different exonic variants and single gene CMVs. Point mutations in STXBP1 and a small CMV in 22q11 will be central at the start of the project.  Other mutations and cell models will be generated during the course of the project using gene-editing methodology, to generate additional models for schizophrenia, autism and mental retardation. In this project, we will analyze synaptic transmission using patch clamp physiology and life cell imaging in these cell models and a variety of other approaches to elucidate disease mechanisms. Studies will be embedded in the SUN consortium and the local STXBP1 research team, composed of scientists with several difference disciplines (clinicians, EEG-experts, cell biologists, see https://stxbp1.cncr.nl). We will also test candidate drugs and candidate genetic therapies to normalize cellular abnormalities observed in these studies and link promising candidate therapies back to the clinicians in our team and collaborators worldwide.

Requirements:

We are looking for candidates that hold, or will soon hold, a master degree in (Medical) Biology, Biophysics or Physics, preferably with hands-on experience in the methods listed above, and a strong motivation to pursue a career in science. Experience with Matlab is an advantage.

Salary Benefits:

A challenging position in a socially involved organization. The salary will be in accordance with university regulations for academic personnel and amounts €2,395 (PhD) per month during the first year and increases to €3,061 (PhD) per month during the fourth year, based on a full-time employment. The job profile: is based on the university job ranking system and is vacant for at least 1 FTE.

The appointment will initially be for 1 year. After a satisfactory evaluation of the initial appointment, the contract will be extended for a duration of 4 years.
Additionally, Vrije Universiteit Amsterdam offers excellent fringe benefits and various schemes and regulations to promote a good work/life balance, such as:
  • a maximum of 41 days of annual leave based on full-time employment
  • 8% holiday allowance and 8.3% end-of-year bonus

Work Hours:

40 hours per week

Address:

De Boelelaan 1105