We work to employ the CryoWriter prototype that our lab purchased from the CryoWrite AG to extract the fibrils contained in a single plaque of a human brain slice affected by neurodegeneration. The CryoWriter has a nanoliter pipette that can be positioned with micrometer precision over a biological specimen on top of an inverted light microscope. We will develop protocols to use this hardware to extract the contents of an individual plaque, such as a Lewy body in a Parkinson's disease affected brain tissue, or a tau tangle in an Alzheimer's disease affected brain tissue, and aspire the fibrillar contents of that plaque into the capillary. This contents will then be "written" onto a cryo-EM grid and rapidly plunge-frozen. Such grids will then be imaged by cryo-EM in order to determine the high-resolution structure of the fibrils contained in that plaque. 

We seek to determine the structure of fibrils from individual plaques, to understand if specific plaques and/or cell types and/or brain regions are always only populated by only one single type (polymorph) of fibrils, or if different fibril strains populate the same plaques.