Quick Project Snapshot
Novel antiepileptic drug targets based on HCN channel antagonists
About 30% of epilepsy patients are not controlled on currently available antiepileptic drugs. Our laboratory has discovered a novel anti-epileptic drug target.
HCN channels are an ion channel in the brain that regulates rhythmic behaviour which is a hallmark of a seizure. In collaboration with Italian scientists we have demonstrated that a compound that blocks a certain subtype of this channel reduces seizures.
Based on this the NIH Anticonvulsant Screening Program in USA will test this compound on a range of seizure models.
In this project we want to begin to understand how blockers of this channel reduce seizures. We have assembled a range of state-of-the-art tools to answer this question. This includes a viral-based knock-down strategy, a conditional knock-out mouse model and pharmacological tools.
In this project the student will learn a range of experimental techniques ranging from behaviour to recording single neuron activity. These channels are also thought to be important to the generation of pain and drugs based on this target may be useful in this condition as well.
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.