Studying Peripheral Neuropathies in Drosophila
We are a highly motivated and multidisciplinary team at the VIB Department of Molecular Genetics (http://www.vib.be/en/research/scientist ... a-Lab.aspx) looking for an enthusiastic postdoctoral researcher to join our lab for 2 years (with possibilities for extension).
Main topic of our lab is studying the molecular mechanisms underlying peripheral neuropathies that are associated with defects in aminoacyl-tRNA synthetases. This field of research stems from our findings that mutations in the tyrosyl-tRNA synthetase (TyrRS), similarly to defects in four other synthetases, cause dying-back degeneration of the peripheral nerves and lead to Charcot-Marie-Tooth disease (CMT). We established that CMT neuropathy is not due to haploinsufficiency of TyrRS enzymatic activity, but to a gain-of-function alteration of the mutant protein or interference with an unknown function of the wild type protein. To gain insights in disease pathology we developed and characterized the first Drosophila model for CMT. Transgenic flies expressing CMT-causing TyrRS mutations have progressive motor deficit, electrophysiological dysfunction and terminal axonal degeneration, thus closely recapitulating the molecular and cellular hallmarks of human disease. Currently, we are applying gain-of-function modifier screens to identify genes, whose function modulates neuron-specific mutant TyrRS phenotypes in flies. The putative modifier genes are functionally characterized using genetic, electrophysiological and molecular biological experimental paradigms with the goal to understand the crucial cellular pathways affected by mutant TyrRS and how this contributes to fly and human neurodegeneration. We further search for common and specific neurodegenerative pathways between TyrRS and the other tRNA- synthetases implicated in CMT disease.
The main methods that are used in our lab are:
- Fly and human genetics, molecular genetics and transcriptomics;
- Behavioral assays in Drosophila using an automated platform;
- Electrophysiological recordings of fly NMJ and GFS;
- Confocal and electron microscopy.
The postdoctoral researcher will be embedded in an ongoing project and will have the opportunity to use characterized transgenic flies, results from modifier screens, transcriptomics data and available patients’ biosamples in order to generate hypotheses and gain original insights on the alternative function(s) of TyrRS and its role in human neurodegeneration.
As part of the Department of Molecular Genetics (http://www.molgen.vib-ua.be) and VIB (http://www.vib.be), the successful applicant will benefit from established collaborations and will have access to centralized facilities with expertise in functional genomics and cell biology, proteomics, cutting-edge microscopy, structural biology, technology development, and bio-informatics. VIB provides a highly interactive environment and ample training opportunities for PhD and postdoctoral researchers. In addition, the VIB Department of Molecular Genetics is located in the city of Antwerp, the capital of Flanders, offering a culturally and historically rich, and ethnically diverse environment.
Postdoctoral candidates are expected to have:
• PhD degree with at least one accepted first-author publication in an international peer-reviewed journal;
• Background in Drosophila (neuro)biology and/or genetics;
• Experience in molecular and cell biology would be an advantage;
• Excellent verbal and written English communication skills
How to apply?
Please e-mail your:
- Detailed CV
- List of publications
- One page description on previous research experience, skills and research interests
- Names and addresses of 2 referees
Contact: More details on the project can be obtained from Prof. Albena Jordanova, PhD (firstname.lastname@example.org)
VIB Department of Molecular Genetics,
University of Antwerp-CDE
Tel: +32-3- 265.10.25