Laboratory of Molecular Neurobiology

The laboratory was established at the Institute of Physiology (IPHYS), Prague in 2014 by Dr. Martin Balastik (Ph.D. at the Max-Planck institute for Biophysical Chemistry, Gottingen, Germany; postdoc Harvard Medical School, BIDMC, Boston, USA). IPHYS is a leading institute in the field of biomedical research in the Czech Republic located at the biggest biomedical research campus in the Czech Republic, only 30 min away from the historical center of Prague.

We study molecular regulation of neural development, in particular the role of microtubule-associated proteins (MAPs) and prolyl isomerases in axon/dendrite guidance and synapse refinement, and how developmental deregulation of these genes contribute to pathogenesis of neurodevelopmental disorders (as autism spectrum disorder, epilepsy or schizophrenia).

The laboratory uses an array of advanced mouse genetic, molecular biology, biochemistry and microscopy techniques, including generation of knockout mice, in utero electroporation, neuron cultures in microfluidic chambers, organotypic slice cultures, lentiviral vector cloning and production, confocal microscopy, super resolution microscopy and advanced image analysis (Neurolucida, Imaris).

Position offered

Following our recent discoveries demonstrating a novel role of CRMP2 in axon and dendritic spine refinement (Ziak et al, EMBO Rep. 2019, Balastik et al, Cell Rep. 2015), we are seeking a postdoctoral researcher with a PhD in molecular biology, neuroscience, biochemisty and related subjects to analyze the role of microtubule associated proteins of CRMP (collapsing response mediator protein) gene family and their isoforms in actin-microtubule crosstalk in growth cones and dendritic spines.

The position is offered for 3 years with a possibility for extension, and provides the candidate with a competitive salary and benefits.

Due to grant requirements, we request the candidates to contact us before January 20th 2020.

Project annotation

Dendritic spines are microscopic protrusions found on neuronal dendrites, which interact with terminal boutons of axons to form synapses. Morphology and number of dendritic spines have a direct effect on synaptic transmission. Changes of density, size and shape of dendritic spines have been linked to multiple neurodevelopmental disorders (e.g. autism and schizophrenia). The morphology of dendritic spines is mainly controlled by actin microfilaments, similarly as the shape of the tips of the growing axons – the growth cones. Molecular mechanisms controlling formation, maintenance or elimination of dendritic spines and rearrangement of growth cones are so far poorly understood.

We have recently demonstrated a novel mechanism regulating axon growth and guidance in vivo through phosphorylation and conformational changes of microtubule associated protein CRMP2 catalyzed by isomerase Pin1 (Balastik et al, Cell Rep, 2015). In order to better characterize the role of CRMP2 in development, we generated and analyzed full- and isoform specific- CRMP2 knockout mice. Surprisingly, we found that in contrast to previously published in vitro data, CRMP2 plays in vivo only a moderate role in embryonic axon guidance, but that it is essential for synapse refinement through processes of axon and dendritic spine pruning (Ziak et al., EMBO Rep, 2019). In addition, we found that CRMP2 deficiency leads to changes of dendritic spine morphology suggesting that CRMP2 is important for regulation of not only microtubules (as demonstrated before), but also actin microfilaments. Actin – microtubule crosstalk is essential for development and function of dendritic spines and growth cones. The successful postdoctoral candidate will test isoform-specific binding of different CRMPs to actin and how they control actin-microtubule crosstalk in dendritic spines and growth cones in vitro and in vivo. The role of CRMP phosphorylation in CRMP-actin interaction will be analyzed in primary neurons and in vivo using the in utero electroporation.

References

• Ziak J, et al., CRMP2 mediates Sema3F-dependent axon pruning and dendritic spine remodeling, EMBO Reports, (2019) accepted, BioRxiv DOI: 10.1101/719617
• Balastik, M, et al, Prolyl isomerase Pin1 regulates axon guidance by stabilizing CRMP2A selectively in distal axons. Cell Reports 2015 Oct 27;13(4):812-28

Benefits

• Social benefits (health insurance, contribution to pension, diets, courses)
• 5 weeks holiday + sick days
• Working in international environment

Offer Requirements

Skills/Qualifications

• Experiences with lab work are required. Knowledge of cell biology, neurobiology, mouse genetics, histology, and microscopy techniques is an advantage.
• CV including publication list, techniques

Application:

Interested candidates can send their motivation letter and CV with the names and contact information of two-three references to email: Marcela.Tomaskova@fgu.cas.cz