Disease mechanisms in a novel mouse model of progressive myoclonus epilepsy

Research Opportunity
Honours, Master of Biomedical Science
Number of Honour Places Available
Medicine and Radiology
Florey Institute of Neuroscience & Mental Health
Primary Supervisor Email Number Webpage
Dr Snezana Maljevic snezana.maljevic@florey.edu.au
Co-supervisor Email Number Webpage
Prof Steven Petrou steven.petrou@florey.edu.au

Project Details

A recurrent mutation, Arg320His, in the KCNC1 gene, encoding voltage-gated potassium channel Kv3.1, has been identified as one of the main causes of progressive myoclonus epilepsy (PME), a rare, inherited disorder manifesting with myoclonus, tonic-clonic seizures, and ataxia. In vitro analysis in Xenopus laevis oocytes revealed that the mutation causes a loss of channel function (Muona et al., Nat Genet 2015).

To provide in-depth analysis of disease mechanisms, we generated knock-in mouse model carrying Arg320His mutation. The project aims at examining properties of neuronal networks derived from this mouse model using multielectrode array (MEA) analysis. To this end, primary neuronal cultures will be plated on MEA dishes and their activity analysed at different time points. We will also examine the effects of elevated temperature on the network activity, as clinical data suggest improvement of symptoms in patients with fever. This platform will be further used to test the efficiency of different drugs, including specific Kv3.1 channel openers, by assessing their impact on the signatures of network activity altered by the mutation.

Apart from cell culture methods and MEA analysis, the project will include Ca imaging of neuronal network activity, as well as immunostaining to assess the localization of mutant channels in neurons. We expect that the obtained results will lead to the clinical translation and precision medicine approaches in the treatment of the affected individuals.

Faculty Research Themes


School Research Themes

Neuroscience & Psychiatry

Research Opportunities

Honours, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.


Medicine and Radiology

Research Node

Florey Institute of Neuroscience & Mental Health

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