Tuberous sclerosis and epilepsy: using resected tissue to understand disease pathogenesis

Research Opportunity
Honours, Master of Biomedical Science
Number of Honour Places Available
1
Number of Master Places Available
1
Department
Paediatrics
Location
Royal Children’s Hospital/Murdoch Childrens Research Institute
Primary Supervisor Email Number Webpage
Associate Professor Paul Lockhart paul.lockhart@mcri.edu.au 03 8341 6322 Personal web page
Co-supervisor Email Number Webpage
Doctor Sarah Stephenson sarah.stephenson@mcri.edu.au 03 9936 6563 Personal web page

Summary 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 combined with our ultra-high field ex vivo diffusion MRI data to create a 3D reconstruction of tubers.

Project Details

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 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 (16.4T) 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 combined with our ultra-high field ex vivo diffusion MRI data to create a 3D reconstruction of tubers.



Faculty Research Themes

Child Health

School Research Themes

Child Health in Medicine



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.

Department

Paediatrics

Research Node

Royal Children’s Hospital/Murdoch Childrens Research Institute

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