Department

Department of Neurochemistry

Head

Martin Horák, PhD

Website

http://www.iem.cas.cz/en/research/departments/department-of-neurochemistry/

Project title

The development of novel pharmacological compounds acting on NMDA receptors

Supervisor

Martin Horák, PhD

Project description

N-methyl-D-aspartate (NMDA) receptors belong to a family of ionotropic glutamate receptors that play a key role in excitatory neurotransmission in the mammalian central nervous system. Alternatively, their dysfunction leads to many neuropathological disorders including neurodegenerative diseases and cognitive deficits. In collaboration with the Biomedical Research Center in Hradec Kralove and the National Institute of Mental Health in Klecany, we will develop a series of compounds based on tacrine and MK-801 that modulate NMDA receptor activity by a unique mechanism. In this PhD project, you will investigate the molecular mechanisms of the modulatory effect of the novel compounds on NMDA receptors, using sophisticated molecular biological and electrophysiological approaches including, for example, whole-cell and single-channel measurements on transfected HEK293 cells, as well as synaptic measurements on autaptic hippocampal neurons infected with lentiviruses expressing mutated GluN subunits. Our goal is to optimize the physicochemical properties of the novel compounds, including their solubility, blood-brain barrier permeability, affinity and rate of action on individual NMDA receptor subtypes, but to minimize their side effects in vivo.

Candidate profile

M.Sc. (Mgr.) degree or equivalent in (bio)chemistry, molecular/cellular biology, neuroscience, physiology or medicine; strong interest in conducting pre-clinical research in the field of glutamate receptors.

Suggested reading

• • Kolcheva et al., Neuropharmacology 189:108528 (2021).
• Gorecki et al., Eur J Med Chem 219:113434 (2021).
• Kaniakova et al., Biochem Pharmacol 186:114460 (2021).
• Hemelikova et al., Neuropharmacology 157:107671 (2019).
• Kaniakova et al., Curr Alzheimer Res 16(9):821-833 (2019).
• Kaniakova et al., Neuropharmacology 140:217-232 (2018).
• Gazova et al., Biochim Biophys Acta Mol Basis Dis 1863(2):607-619 (2017).
• Horak et al., Prog Neuropsychopharmacol Biol Psychiatry 75:54-62 (2017).

Application form