Postdoc - Translational Strategies for Lymphatic Anomalies in RASopathies

Postdoc - Translational Strategies for Lymphatic Anomalies in RASopathies

Hubrecht Institute

Utrecht, Netherlands

€ 3.546 - € 5.538 per month gross

Project description

In the framework of a ZonMW-funded project entitled: “Translational strategies for lymphatic anomalies in RASopathies”, there is an opening for a postdoc in the den Hertog lab. The RASopathies form a group of human syndromes that are characterized by similar symptoms (short stature, craniofacial defects, cardiac defects and enhanced susceptibility to cancer) and are caused by activating mutations in factors of the RAS-MAPK signaling pathway. Noonan syndrome (NS) is one of the most common RASopathies and 50% of NS patients have an activating mutation in SHP2, a protein-tyrosine phosphatase encoded by the PTPN11 gene. To understand the molecular-genetic and cellular basis of NS at the organismal level, we study zebrafish. We have introduced mutations in zebrafish ptpn11 and other NS-associated genes, sos1 and sos2, using CRISPR/Cas9 technology and Homology-Directed Repair. Initial characterization suggested that these zebrafish NS models recapitulate symptoms in human NS patients. In this project, the focus will be on defects in the lymphatic vasculature, which is a major problem in human NS patients. We will investigate genotype/phenotype correlations in zebrafish NS models and study the mechanism underlying defects in the lymphatic vasculature. Moreover, we will use therapeutic drugs to ameliorate the lymphatic defects in zebrafish NS models. This approach will highlight how pharmacological intervention rescues development of lymphatic structures.

Requirements

You have a PhD in molecular biology, cell biology, developmental biology, molecular genetics or similar. Experience with zebrafish is not required, but is preferred. You have affinity with cellular signal transduction and with multidisciplinary research.