Tuberous sclerosis and epilepsy: using resected tissue to understand disease pathogenesis
- Research Opportunity
- Honours, Master of Biomedical Science
- Number of Honour Places Available
- Number of Master Places Available
- Royal Children’s Hospital/Murdoch Childrens Research Institute
|Associate Professor Paul Lockhartfirstname.lastname@example.org||03 8341 6322||Personal web page|
|Doctor Sarah Stephensonemail@example.com||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.
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
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 NodeRoyal Children’s Hospital/Murdoch Childrens Research Institute
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