Confocal Microscopy
I perform confocal microscopy to visualize live and fixed cellular samples. I have used this method to track the rapid uptake of α-synuclein fibrils and spike protein. Confocal live imaging also enabled me to track lysosomal function under cytokine stress, showing how IFN-γ impaired degradation pathways and promoted Lewy body–like inclusion formation
SARS-CoV-2 Internalization Paper
Confocal microscopy was key to this work because it let me track how the SARS-CoV-2 spike protein bound to the cell surface and was taken up into the cell. By using fluorescent labeling and acid washing (which disrupts receptor-ligand interaction), I could distinguish surface binding from true internalization, showing that uptake was ACE2-dependent and occurred through clathrin-mediated endocytosis.
Super-Resolution Microscopy (STED)
To surpass the resolution limits of confocal imaging, I used STED microscopy to resolve sub-lysosomal localization of fibrils. This revealed α-synuclein in the lumen of lysosomes and within multivesicular bodies, providing ultrastructural confirmation of macropinocytic trafficking. STED was also critical for visualizing Parkin translocation to damaged mitochondria in real time, highlighting its utility in organelle quality control studies.
