The Institute of Molecular and Clinical Ophthalmology Basel (IOB) is seeking a highly motivated Research Assistant to join the Retinal Organoid Platform. IOB is a research institute combining basic and clinical research. Its mission is to drive innovations in understanding vision and its diseases and develop new therapies for vision loss. It is a place where your expertise will be valued, your abilities challenged, and your knowledge expanded. The Retinal Organoid Platform uses human retinal organoids derived from pluripotent stem cells as models for inherited retinal degeneration. Therefore, the Retinal Organoid Platform is involved in collecting and reprogramming into iPSC cells from patients with retinal disease as a resource for IOB researchers and collaborators around the globe. Furthermore, the Retinal Organoid Platform is introducing precise patient mutations into hiPSC by genome engineering. Your responsibilities: - In vitro culture of human induced pluripotent stem (iPSC) cells and retinal organoids - Gene editing of iPSC by CRISPR/Cas9, and full characterization of mutant cells - Characterization of iPSC and retinal organoids by various histology, molecular biology and microscopy techniques - Vector construction and molecular cloning - Applying and improving new methodologies to enhance the creation of mutant iPSC - Reprogramming of human primary cells to iPSC - Biobanking of primary cells and iPSC - Involvement in lab management and organization - Close collaboration with group members and IOB groups

The development of the iPS cell technology has revolutionized our ability to study development and diseases in defined in vitro cell culture systems. The talk will focus on Rett Syndrome and discuss two topics: (i) the use of gene editing as an approach to therapy and (ii) the role of MECP2 in gene expression (i) The mutation of the X-linked MECP2 gene is causative for the disease. In a female patient, every cell has a wt copy that is, however, in 50% of the cells located on the inactive X chromosome. We have used epigenetic gene editing tools to activate the wt MECP2 allele on the inactive X chromosome. (ii) MECP2 is thought to act as repressor of gene expression. I will present data which show that MECP2 binds to Pol II and acts as an activator for thousands of genes. The target genes are significantly enriched for Autism related genes. Our data challenge the established model of MECP2’s role in gene expression and suggest novel therapeutic approaches.