PhD Student - Myotonic Dystrophy

PhD Position in the development of a novel cell-based strategy for the neuromuscular phenotype in a myotonic dystrophy mouse model


 Myotonic dystrophy (dystrophia myotonica, DM1) is a multisystemic neuromuscular disorder with progressive myotonia, muscle weakness and neurological symptoms impacting the quality of life of affected individuals. The genetic basis of DM1 - a CTG-repeat expansion in the 3' untranslated region of the DMPK gene - was elucidated in 1992, but so far no treatment is available. In this project we will initiate a preclinical study aimed to develop a new strategy for therapeutic intervention in DM1.

Our proposal combines two novel methodologies that are geared towards the development of an innovative cell-based therapeutic strategy using genetically-corrected autologous stem cells. One novel arm of our approach involves the use of specific mesenchymal stem cells, pericytes, which have the propensity to colonize muscle tissue and differentiate to myogenic lineage that can contribute to regeneration of the dystrophic muscle. The other arm is the use of CRISPR/Cas9 for specific and highly efficient genetic excision of the repeat mutation in cultured pericytes. The genetically-corrected cells will be injected in hindlimb muscles of myotonic transgenic mice carrying a human CTG-repeat-containing transgene. The potential in vivo myogenic effects will be analyzed by studying the physiology, histology and performance of transplanted muscle.

The final goal of our project is to provide proof-of-concept for the use of pericytes in cell-based therapy of the muscular deficiencies seen in DM1. The proposed preclinical studies are a mandatory prelude to commence with clinical trials.
Organization
This 4-year PhD project is funded by Radboudumc and the Donders Centre of Neuroscience. The successful candidate will be employed at the Department of Human Genetics and participate in the Graduate School of the Donders Institute for Brain Cognition and Behaviour. This is a multidisciplinary project involving three Departments: Human Genetics, Neurology and Cell Biology. A training in pericyte extraction and culturing is foreseen early in the project at the Department of Clinical Genetics, Maastricht UMC.

Desired skills and experience

Profile

• The candidate should have a master's degree (or equivalent) in the field of molecular life sciences
• Background in molecular and cellular biology
• Experience in molecular and cellular techniques, cell culture and microscopy
• Willing to learn or have experience in working with laboratory animals
• Motivation, initiative and ambition to publish in high-impact journals
• Able to work in a multidisciplinary team as well as independently
• Excellent communication skills, contributing to a pleasant working atmosphere
• High level of proficiency in English; basic knowledge of or willingness to learn Dutch

Comments and contact information
Conditions of employment

• Employment will initially be for one year, and can be extended with an additional 3 years after a positive evaluation.
• Salary is € 2222 gross per month in the first year up to a maximum of € 2846 gross per month in the last fourth year (scale PhD), plus additional vacation bonus (8% per year) and end of year payments (8.3% per year).
• The employment for this position will start first half of 2016.

Application
To submit your application online. Qualified applicants are requested to send a letter describing their interest in the position, qualifications, experience and career goals, as well as a CV with full publication list and the names and contact information of two references.
Information
For information please contact Prof. Dr. Hans van Bokhoven, Human Genetics, Hans.vanbokhoven@radboudumc.nl, +31 (0)24- 361 40 17 or Prof. Dr. Baziel van Engelen, Nurology, Baziel.vanengelen@radboudumc.nl, +31 (0)24-361 43 08. (These e-mail addresses are to be used for information purposes only)

Working at Radboudumc
Radboudumc aims to be at the forefront of the development of innovative, sustainable and affordable healthcare. Our mission is 'to have a significant impact on healthcare'. We believe we can achieve that by providing excellent quality, participatory and personalized healthcare, operational excellence and by working together in sustainable networks. The starting point for this is patients and their quality of life. Throughout all this, patient care, research and education go hand in hand.

To realize our mission, we are searching for colleagues who want to take on this challenge with us; employees who are excellent in their field of expertise and give it their all by pushing boundaries and providing 'that little bit more'. At Radboudumc, you gain the confidence, receive and take responsibility to successfully make these changes. For the best patient care and the best future of healthcare.

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