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PhD-project: Cellular and synaptic phenotyping of human neurons from children with ASD

Research / Academic
Amsterdam
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. 

Autism spectrum disorder (ASD) is a developmental disorder for which currently no general effective therapy exists. This project is part of a larger program “New, rational therapy decisions for developmental brain disorders: Integrating quantitative patient assessment, cellular assays and nanotechnology (NewTDec)”, and is among the first projects to operate under the Dutch research agenda (www.wetenschapsagenda.nl). NewTDec is a multidisciplinary consortium in which clinicians, neuroscientists, nanoscientists and patient organizations collaborate to develop new methods to identify biological causes for autism with the aim to develop personalized medicine for children with ASD. Quantitative assessment of brain functions using predictive EEG ‘signatures’ for individual patients and cellular assays using patient-own, stem cell-derived neurons will be used to measure specific brain characteristics in the same patient. This information is used in clinical trials to match patients with an optimal, individual therapy and to develop novel therapies for specific patient subgroups in the future.

   

In this project we will use patch-clamp electrophysiology to study synaptic transmission and neuronal function in networks from inducible pluripotent stem cells (IPSCs) derived neurons from children with ASD. We will specifically investigate cellular and synaptic parameters that affect the balance between excitation and inhibition (E/I) in these networks. One of the leading hypotheses is that E/I balance is disturbed in neurodevelopmental disorders such as ASD, leading to altered information processing in the brains of these patients. We will test if and how cellular and synaptic parameters are changed in patients that have been selected for a putative altered E/I balance, based on biomarkers obtained from their EEG profile. Furthermore, we will test how these parameters are affected by various E/I modifying drugs. This information will eventually be used to inform N=1 clinical trials in the same patients. You will be trained on site and in specialized courses on campus. During the PhD you will write several scientific publications that will be combined in a PhD thesis.

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