|| The Experimental Research Unit of the Department of Thoracic and Cardiovascular Surgery of the University Medical Centre Göttingen invites applications for a
PhD student position on modelling early-onset cardiomyopathies in vitro using RASopathy patient-derived induced pluripotent stem cells (m/f/d)
The objective of this PhD project is to identify pathological phenotypes in a 3D model of functional human myocardium based on induced pluripotent stem (iPS) cells derived from patients with mutations in the RAS-MAPK pathway. In a second step, phenotype rescue experiments will be performed, including efficacy and safety testing of highly specific compounds.
In our group, we focus on the effects of heterozygous mutations in genes of the RAS-MAPK pathway. In humans, these mutations result in syndromes that belong to a family of rare diseases called the “RASopathies”. Next to other clinical anomalies, affected individuals show certain organotypic abnormalities including an increased tendency towards cardiomyopathies at early developmental stages ranging from mild to lethal. Although knowledge about mutated genes and associated phenotypes is growing constantly, understanding of their exact role in disease development, progression and physiology remains incomplete. Hence, deciphering impaired interactions between affected signalling networks and their effects on the phenotype may serve as a basis for future therapeutic strategies. We approach this task by employing patient iPS cell-derived cardiomyocytes for 3D myocardial tissue engineering that mimics an in vivo-like environment and fosters tissue maturation. Using state-of-the art customized bioreactor systems, long-term cultivation, stimulation and characterization provide us with detailed insights into (electro-)physiological, morphometric, histological and biochemical properties of myocardial organoids and help us identify putative mutation-associated phenotypes. In-depth comparisons with unrelated healthy and gene-corrected isogenic controls allow us to unambiguously determine causality between studied mutation and observed phenotypes. This experimental environment is also employed for initial efficacy and safety testing of pharmaceutic compounds for mutation-specific in vitro phenotype rescue approaches.
We offer an attractive work environment within the German Centre for Cardiovascular Research (DZHK e.V.) at the partner site Göttingen and its associated facilities. Next to a broad collaborative network nation-wide and within the University Medical Centre Göttingen, we are supported by the local Stem Cell Unit with state-of-the-art techniques for nuclear reprogramming and genome editing. All applied methods are well established in our multidisciplinary working group. The current project is part of a national research consortium (German Network for RASopathy Research, GeNeRARe) and is funded by the German Federal Ministry of Education and Research (BMBF) for 36 months.
We are searching for a PhD student with a strong background in life sciences like biology, biochemistry, biomedical sciences or comparable. Next to having substantial knowledge in standard biochemical and molecular biology techniques and excellent oral and written scientific communication skills, the ideal candidate for this position is well organized, self-motivated and independent. Previous experiences in (iPS) cell culture and myocardial differentiation are helpful but not mandatory.
Please send your application as PDF in German or English including cover letter, CV, short outline of research experiences (max. 1 page), publication list (if applicable), contact details of at least one referee and relevant certificates (see contact details below).
Women are especially encouraged to apply. Applicants with disabilities and equal qualifications will be given preferential treatment.
Travel and application fees cannot be refunded or transferred.
We look forward to receiving your application by May 31st, 2019.
University Medical Centre Göttingen
Department of Thoracic and Cardiovascular Surgery
George Kensah, PhD
Head of Experimental Research