27.1. 2020, Laboratory of Cellular Neurophysiology

Laboratory of Cellular Neurophysiology

PhD project: Triheteromeric NMDA receptors – physiological and pathophysiological functional properties

Ionotropic glutamate receptors (iGluRs) mediate excitatory synaptic transmission and are essential for processes of learning and memory formation.  Dysfunction of tetrameric AMPA and NMDA receptors (NMDAR)  underlies many neurological disorders including schizophrenia, epilepsy or autism. In our current study, we have identified several genetic variations in the regulatory part of genes encoding human NMDAR subunits and also various nonsynonymous mutations in exons encoding modulatory N and C-terminal parts of the receptor. In both cases, the impact of non-coding variations, and some mutations on the receptor expression, biogenesis and functional properties has not been described in details.

The aim of the proposed PhD project will be i/ to test the effect of variations in regulatory parts of the gene on the NMDAR mRNA expression and localization. ii/ to characterize, at the molecular (bioinformatics and structural studies) and cellular level (expansion and high-resolution microscopy, electrophysiology) the influence of mutations on the biogenesis, localization, and function in the di and triheteromeric assembly of NMDAR.

Candidate’s profile (requirements):

Candidates should have a Masters' degree in biological, medical, chemical and or bioinformatics subjects. Experience in molecular biology, cell biology, electrophysiology or human genetics would be an advantage. 

Supervisor: RNDr. Ales Balik, PhD.

Relevant publications:

Cerny J. et al, NMDA Receptor Opening and Closing-Transitions of a Molecular Machine Revealed by Molecular Dynamics. Biomolecules. 2019

Marek L. et al,  The LILI Motif of M3-S2 Linkers Is a Component of the NMDA Receptor Channel Gate . Frontiers in Molecular Neuroscience 2018

Vyklický V. et al,  Surface Expression, Function, and Pharmacology of Disease-Associated Mutations in the Membrane Domain of the Human GluN2B Subunit . Frontiers in Molecular Neuroscience 2018