PhD-student in Cellular and synaptic phenotyping of human neurons from children with ASD

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 project 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 (IPSC's) 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 hypothesis 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.