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TUBEROUS SCLEROSIS AND EPILEPSY: USING RESECTED TISSUE TO UNDERSTAND PATHOGENESIS
Tuberous sclerosis complex (TSC) is a multisystem disorder leading to benign tumours in multiple organs including the skin, kidneys, heart, lungs and brain. The most significant clinical features of TSC are neurological, with epileptic seizures being the most common and severe, particularly when they occur in early childhood. Seizures from TSC are often drug-resistant and incomplete control, especially during early childhood, is associated with adverse developmental consequences including intellectual disability and autism.
The seizures of TSC originate in dysplastic lesions known as cortical tubers. Tubers are well circumscribed and usually confined to a single gyrus, often extending into the subcortical white matter. They are characterised by disorganised cortical lamination and abnormal cells including dysmorphic neurons and balloon or giant cells. Our recent experience with modelling tuber microstructure using ultra-high field (16.4 Tesla) ex vivo diffusion MRI acquired from the resected tuber specimens also plausibly demonstrated localisation of dyslaminated cortex and dysmorphic neurons in the tuber centre.
This suggests that it is the tuber centre that is likely to contain the highest density of dysmorphic neurons. We have qualitative data from visual analysis of tubers using routine histopathological techniques to support this, however neither we nor any other group have systematically tested this hypothesis by quantitative analysis of the density of dysmorphic neurons in various regions of a tuber. In this project, the candidate will use immunostaining and stereological techniques to determine the gradient density of dysmorphic neurons in resected tuber tissues. These histology findings will be overlayed with our ultra-high field ex vivo diffusion MRI data to create a 3D reconstruction of tubers.
Ion Channels and Human Diseases Laboratory
Our research focuses on understanding the pathology of ion channel disorders, in particular epilepsy, using in vitro and in vivo models to reveal opportunities for developing novel therapies. We use a multidisciplinary approach spanning ion channel biophysics, mouse transgenesis, genetic analysis, computational modeling and in vitro and in vivo electrophysiology.
All Projects by this Lab“CLARITY” based glass brain imaging in health and diseaseNeuroanatomical determinants of susceptibility in a model of genetic epilepsyMulti-site patch clamp recording of cortical micro networksProjects in network analysis of genetic epilepsyHigh content automated analysis of ion channels in epilepsyHigh density multi-electrode array recording of in vitro networks in epilepsyIn vivo electrophysiological analysis in mouse models of genetic epilepsyMRI tractography in mouse models of genetic epilepsy: Creation of prognostic and diagnostic structural biomarkersOptogenetic modulation of the area tempestas – an epilepsy hot spotTUBEROUS SCLEROSIS AND EPILEPSY: USING RESECTED TISSUE TO UNDERSTAND PATHOGENESIS
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.