Interdisciplinary PhD position in iPSC modelling of human hyperkinetic disorders in Zürich

The Bio Engineering laboratory (BEL) is inviting applications for a PhD position at the intersection of human cellular modelling, large-scale electrophysiology and multi-modal data analysis. The project is part of the EUROPEAN JOINT PROGRAMME RARE DISEASES (EJP RD) and is aimed at developing new analytic tools to study pathways and accelerate the diagnosis of rare hyperkinetic disorders. The PhD project will be carried out at the ETH Zurich Department of Biosystems Science and Engineering (D-BSSE) in Basel and involves close collaboration with several other research institutions in the EU.

The position is planned for 3-4 years (PhD), the starting date of the project is 1st of July 2023.

Dystonias encompass a heterogenous group of rare hyperkinetic movement disorders. Leveraging the advance in genetic technology, researchers have been able to elucidate the genetic cause of various monogenic forms of dystonia, revealing different pathogenic mechanisms. However, in most cases the genetic diagnosis fails, hindering the understanding of the pathogenesis, and, thereby, obviating accurate prognosis and the development of targeted therapeutic approaches. In this project, we aim to increase the diagnostic yield in dystonias and to study some variants in 3-D human iPSC-derived cellular models. We will employ clinical cohorts, large collections of samples, and patient-derived organoid models to probe dystonia features at the molecular level and to identify prognostic markers for a better treatment of these disorders.

For the work package involved in the systematic molecular and functional characterization of human cellular models of dystonia, we are looking for a motivated PhD student. The main tasks of this project include: 

• Development of protocols to study dystonia in 3-D human iPSC-derived brain organoids.
• Functional characterization of brain organoid development with large-scale electrophysiological means (e.g., high-density microelectrode arrays).
• Applying immunohistochemistry and single-cell genomic methods to study human cellular models of dystonia.

• You should have a background in either neuroscience, stem cell biology or molecular/cellular biology.
• Desirable skills include expertise in cell cultures, immunohistochemistry, electrophysiology, and knowledge of statistical data analysis.
• You must be able to fluently communicate in English and be willing to work in a highly interactive international team. Academic excellence, a professional work attitude and a proactive and self-driven nature are expected.

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