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
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
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
For further information about this research, please contact a supervisor.
Research NodeFlorey Institute of Neuroscience & Mental Health
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