Platform of iPS C-derived neurons

SP4: Modellierung von Dystonie in einem endogenen humanen Zellsystem: Plattform und Charakterisierung von iPS-abgeleiteten Neuronen von Patienten mit monogenetischer isolierter Dystonie

- deutscher Text in Kürze -

Projektleitung: Philip Seibler
Partner: Christine Klein
Partner: Lorenz Müller

The research covered in this project is twofold, first to build up a repository for biomaterial from dystonia patients and second to use this material for disease modeling. The biorepository will contain skin fibroblasts and stem cells from patients with different forms of genetic and non-genetic dystonia. We will employ a new technique by using patient-derived skin cells that are reprogrammed into induced pluripotent stem cells (iPSCs).

We intend to differentiate iPSCs from a specific subset of patients with monogen ic isolated dystonia into the diseased cell type, dopaminergic and striatal neurons.

These neurons will be investigated by electrophysiological measurements that will lead to a better understanding of the disease biology and may allow for the development of drug screening assays.

The objectives are:

  1. To build up a biorepository of fibroblasts and iPSC lines from patients with different forms of genetic and non-genetic dystonia
  2. To differentiate iPSCs from patients with TOR1A (DYT1), THAP1 (DYT6), and GNAL (DYT25) mutations into dopaminergic and striatal neurons
  3. To characterize these neurons in a multimodal fashion (calcium imaging, electrophysiology)