Quick Project Snapshot
Zinc and seizures
BENCH TO BEDSIDE - MEDICAL RESEARCH
University of Melbourne at Royal Melbourne Hospital Honours/MBiomedSc Projects 2017 41
Zn2+ is an essential element having a multitude of biological functions throughout the body. Our research has demonstrated that low brain Zn2+ can increase seizure susceptibility (Hildebrand et al 2015 Sci Rep). This highlights Zn2+ supplementation as a potentially good therapeutic strategy for seizure conditions. Before clinical trials can begin we need to complete important pre-clinical work in rodent models of epilepsy. We also need to better understand the mechanisms through which Zn2+ modulates neuronal excitability. In this project the student will learn a range of experimental techniques aimed at understanding the role Zn2+ plays in changing neuronal excitability. This will include using established rodent models to test diet and drug manipulations of brain Zn2+ levels on seizure susceptibility and electrophysiological investigations looking at how neuron excitability is changed by Zn2+. The results have particularly relevance for developing countries, where epilepsy rates are high and nutritional supplementation is a potential practical therapy.
Neurophysiology of Excitable Networks Laboratory
The Neurophysiology of Excitable Networks Laboratory is focused on understanding the basis of neuronal excitability especially in the context of epilepsy. The laboratory is funded through a large NHMRC Program Grant (2015-20) that involves close collaborations with clinical colleagues.
Epilepsy affects up to 4% of the population at some time in their lives. There are major challenges in clinical epilepsy care with at least 30% of patients resistant to current therapies. Even amongst those patients whose seizures are controlled, major issues of drug side-effects and co-morbidities often affect quality of life. Clinical and geneticist colleagues have discovered more than 30 genes associated with epilepsy with more getting discovered each month. However, knowing the genetic cause of epilepsy is not sufficient to tell you how seizures or epilepsy co-morbidities (eg learning difficulties) occur. A mutation in a protein can have its impact on several temporal and spatial scales and understanding the cellular consequence of these changes is central to our understanding, and eventual treatment, of epilepsy. The Neurophysiology of Excitable Networks Laboratory uses a range of experimental techniques to investigate dysfunction at each of these scales. In particular we use single-cell electrophysiology methods to directly measure neurons excitability. We also use state of the art imaging and molecular methods.
The laboratories major recent discoveries have come in understanding the genetic epilepsies. Using mouse models of epilepsy based on human mutations we have identified new disease mechanisms (Brain 2014), as well as explaining some of the complexity of the genetic architecture of the epilepsies (Neurology 2013). Evidence that targeted therapy based on cellular mechanism can be effective in these rodent models exemplifies an exciting paradigm in which precision medicine in the epilepsies can advance.
All Projects by this LabZinc and seizuresNovel antiepileptic drug targets based on HCN channel antagonists
The Florey's Epilepsy division is a world-leading centre for epilepsy research. The division has major groups at both the Florey’s Austin and Parkville campus. The group studies mechanisms that cause epilepsy from the level of cells to the function of the whole brain. We use technologies including advanced MRI and cutting edge cellular physiology techniques to allow us to understand genetic and acquired mechanisms that give rise to epilepsy. Together with our colleagues from The University of Melbourne and across Australia we are working towards finding a cure for epilepsy.