BMI Seminar // Sonia Gandhi - Thinking big to see small: from macroscopic to nanoscopic resolution of Parkinson’s disease

Neurodegenerative diseases are incurable progressive brain disorders that are characterised by the common feature of proteinopathy: the abnormal accumulation of aggregated proteins. My laboratory’s research program focusses on understanding how, where and why proteins misfold in human cells and brain, and how this affects organellar homeostasis, and function, and ultimately leads to neuronal death. We have adapted a range of single molecule and super resolution approaches to study the earliest stages of protein self assembly and aggregation in human neurons and glia, and we have described the factors that influence the kinetics of the aggregation process. We have studied the functional consequence of different protein aggregates in human patient derived iPSC derived neurons and glia, and reported mechanisms by which oligomeric species can induce toxicity. Funded by the global initiative, Aligning Science Across Parkinson’s, we are now integrating single cell genomics, single molecule imaging, and spatial technologies to generate a detailed molecular and cellular map of the human Parkinson’s brain. Our approach models Parkinson’s across different scales and modalities, integrating cellular, computational, and clinical neuroscience to understand causation and progression in Parkinson’s.