17.2. 2023, Molekulární neurobiologie

Laboratory name: Molecular Neurobiology

Laboratory website

PhD project: Microtubules and microtubule associated proteins in dendritic spine formation and refinement

Development of the nervous system is a highly-coordinated interplay of multiple processes including, neuronal polarization, pathfinding of neurites to their targets and synaptogenesis. The developing nervous system is then refined in processes like pruning and through structural plasticity of dendritic spines. A key factor underlying the diversity of the above-mentioned cellular processes is the precisely coordinated remodeling of the neuronal cytoskeleton, which is dominated by changes of actin and microtubules (MT) activity. This coordination is particularly important in the cell regions of high structural plasticity and dynamics, which are in the developing neurons represented by active growth cones (dynamic tips of growing axons and dendrites) and dendritic spines (small protrusions of dendrites). The coordination of actin and MT cytoskeleton in growth cones and dendritic spines is regulated by proteins interacting with both actin and MTs. Unfortunately, the mechanisms by which these proteins dynamically control structural plasticity of the developing neurons and how their defects contribute to the neurodevelopmental disorders are still ill understood.

The aim of the PhD project is a detail analysis of the unique role of microtubule associated proteins (e.g. the isoforms of CRMP2) in dendritic spine formation and refinement. In order to reach this goal, the selected PhD student will perform an array of in vitro molecular biology experiments, cell cultures of primary neurons in microfluidic chambers, histology analysis, as well as in vivo experiments using mouse knockout lines and transgenic mouse models. The project will uncover new molecular mechanisms critical in synapse formation during neural development, as well as in the pathogenesis of neurodevelopmental disorders.

References:

Maimon R, et al, A CRMP4-dependent retrograde axon-to-soma death signal in amyotrophic lateral sclerosis EMBO J, 2021, Sep 1;40(17):e107586
Ziak J, et al, CRMP2 mediates Sema3F-dependent axon pruning and dendritic spine remodeling, EMBO Rep, 2020 Mar 4;21(3):e48512.
Magiera MM, et al,. Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport. EMBO J. 2018 Dec 3;37(23).

Supervisor (email): Martin Balaštík (martin.balastik@fgu.cas.cz)

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 should 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.