Parkinson’s disease (PD) is the fastest-growing chronic neurological disorder affecting 10 million people worldwide. Current therapies are purely symptomatic and do nothing to stop disease progression. We know that alpha-synuclein (α-syn) aggregate formation plays a crucial role in toxicity and progressive neurodegeneration. Still, it does not explain the variability in cell types affected and symptoms observed in PD patients.
The recent identification of fibrillar α-syn aggregates with noticeable differences in structural and phenotypic traits led to the hypothesis that different α-syn 3D conformations or ‘strains’ may be in part responsible for the heterogeneous nature of PD. By exposing cells to different α-syn strains, we aim to identify the gene changes and evaluate the role of those genes as potential therapeutic targets for Parkinson’s disease. Ultimately the goal is to reduce the burden of α-syn in the brain.
As a collective lab, we are investigating these early changes in human brain tissue and primary patient-derived brain cells so we can find ways to delay or stop them before they become a problem.
Immunohistochemistry (IHC) allows us to visualise and analyse the complex distribution and localisation of cellular components within cells in situ.
Multiplex fluorescence IHC facilitates the simultaneous labelling of up to 90 discrete markers of interest on the same tissue section.
We routinely conduct experiments using human brain that are cultured from donated human brain tissue. This is made possible through The Neurological Foundation Human Brain Bank and the Hugh Green Biobank.
Real-time Quaking Induced Conversion (RT-QuIC) is an in vitro assay that permits the strain-specific aggregation and amplification of α-synuclein aggregates derived from human brain tissue or other bodily fluids.
High content tissue screening
Tissue microarray is a technique of arraying cores of tissue (in our case human brain tissue) into blocks that can then be cut and used for histological, immunohistochemical, immunofluorescence and in situ hybridization studies.