内梅亨大学神经节瘤研究博士后职位

日期:2015-01-10
Pheochromocytomas and paragangliomas (PGLs) are rare tumors of parasympathetic and sympathetic paraganglia. Besides being tumors sympathetic PGLs secrete excess catecholamines giving severe headache panic attacks arrhythmias and hypertension.

Pheochromocytomas and paragangliomas (PGLs) are rare tumors of parasympathetic and sympathetic paraganglia. Besides being tumors, sympathetic PGLs secrete excess catecholamines, giving severe headache, panic attacks, arrhythmias and hypertension. Germline mutations in 12 genes confer susceptibility for PGL development in 25-40% of sporadic tumors, which fall into two clusters leading to hypoxia-inducible factor-factor -HIF1/2-alpha- dependent tumorigenesis. Cluster 1 genes involve inactivating mutations in proteins of the Krebs cycle, such as succinate dehydrogenase(SDH) subunits A-D. Most metastatic PGLs are associated with germline mutations in SDHB and predispose to malignancy in 37-97% of the cases. Treatment for SDHB PGLs, however, is lacking and thus appropriate model systems and specific therapeutic targets for these tumors are urgently needed.The goal of the present project is to set up a proper adrenal cell and zebra fish model for SDHB PGLs using CRISPR/TALEN technology and to use these models to study the aetiology of the disease and to screen/test potential therapeutics. Moreover, we will set up a cellular system to screen for inhibitors of a potential therapeutic target and test the effect of its blockers on the SDHB phenotype in our cell/fish models.The project is part of an international collaborative consortium and is a collaborative project of the department of Internal Medicine and Physiology. The department of Internal Medicine has a long-standing tradition to molecularly analyse and treat PGL patients, whereas the department of Physiology has a strong expertise in molecular, cellular and animal pathophysiology. In this project, the applicant will work within the dept. Physiology, which is, together with basic science and research-oriented clinical departments of the Radboud University Medical Center, housed in the "Radboud Institute for Molecular Life Sciences (RIMLS, www.rimls.eu)", which integrates diverse scientific expertise in molecular and medical science for the advancement and innovation in translational research.Major research responsibilities for this position: adrenal cell line and Zebra fish Biochemical analysis for the PGL phenotype in cells/Zebra fish Setting up a cellular screening system for the potential therapeutic target Data analysis and interpretation Contribution towards preparation and submission of manuscripts Presentation of data and communication with research partners  
Description
The ideal candidate has: A PhD in molecular/cellular physiology/endocrinology or related field A permit to work with animals (art. 9) Preferentially experience in using CRISPR/TALEN technology in and breeding/maintenance of Zebra fish Good track record of scientific publications Structured working style Good English writing and presentation skills A strong motivation, flexibility, and willingness to learn The ability to work and interact with others in an energetic and supportive research group

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