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Molecular mechanisms in cortical development and its malformations - the role of microtubule associated proteins

Laboratory name: Molecular neurobiology

Project Supervisor: Martin Balastik, Ph.D. (      

PhD project: Molecular mechanisms in cortical development and its malformations - the role of microtubule associated proteins

Development of the cerebral cortex requires a highly-coordinated interplay of multiple processes including neuron migration, polarization, guidance, synapse formation and refinement. A key factor underlying the above-mentioned processes is a precisely regulated remodelling of the neuronal cytoskeleton, which is dominated by changes of actin and microtubule activity. Microtubules seem to play a particularly important role in cortical development since multiple gene mutations in tubulin or microtubule-associated proteins (MAPs) have been associated with malformations of cortical development (MCD). Unfortunately, the effect of most of the MCD-associated MAP mutations on microtubule dynamics or neural development are still largely unknown.

We have recently shown that microtubule-associated protein CRMP2 (Collapsin response mediator protein 2) controls synaptic pruning in early postnatal stages and that its deficiency shares histological and behavioral features of autism spectrum disorder.

The aim of this PhD project is to functionally characterize new MAP gene variants identified by deep gene sequencing of patients with MCD. Using biochemical and molecular biology techniques the PhD student will generate new cellular (primary neuron) and organismal (mouse) models and analyze the function of the new MAP variants by molecular, histological, and state of the art microscopy techniques. The project will uncover new molecular mechanisms in cortical development and in the pathogenesis of neurodevelopmental disorders.

Candidate’s profile (requirements):

We are seeking outstanding self-motivated candidates with master's degree or equivalent in molecular biology, biochemistry, physiology, medicine or related fields, or those expecting to obtain their degree this year. Candidates must be fluent in English. Experience with in vivo models (mouse, rat) as well as with in vitro cell cultures and molecular biology techniques are advantage.


  • Maimon R, Ankol L, Gradus Pery T, Altman T, Ionescu A, Weissova R, Ostrovsky M, Tank E, Alexandra G, Shelestovich N, Opatowsky Y, Dori A, Barmada S, Balastik M, Perlson E. A CRMP4-dependent retrograde axon-to-soma death signal in amyotrophic lateral sclerosis. EMBO J. 2021 Jun 30:e107586.
  • Ziak J, et al, CRMP2 mediates Sema3F-dependent axon pruning and dendritic spine remodeling, EMBO Rep, 2020 Mar 4;21(3):e48512.
  • Balastik M, et al., Prolyl Isomerase Pin1 Regulates Axon Guidance by Stabilizing CRMP2A Selectively in Distal Axons. Cell Rep. 2015 Oct 27;13(4):812-28.