Alpha-synuclein is a protein localized at the pre-synapse of neurons whose dysfunction is associated with Parkinson’s Disease. The pre-synapse is 0.5-1 μm in diameter, and it contains densely packed vesicles which fuse to the membrane to release neurotransmitters. A-syn binds vesicles at its N-terminus and also at its C-terminus when bound to calcium, and it is proposed to have a role in vesicle recycling; however it is not clear if it is involved in SNARE/clathrin-mediated (CM) exo/endocytosis or kiss-and-run. In collaboration with the Molecular Neuroscience Group, we use quantitative single molecule localisation microscopy to clarify a-syn’s spatial relationship to endocytosed vesicles.

I developed a software package to automatically detect synapses in super-resolution imaging, correct for artifacts arising from chromatic aberrations and high densities of fluorescent emitters, and apply coordinate-based colocalization methods to quantify spatial relationships between protein distributions at the synapse. The beta version of the software can be found in my Github repository.

This is a currently developing project. Below find my poster presented at the 2020 Biophysical Society Meeting on this work.

poster-synaptosomes