The Role of Brain Lymphatic Endothelial Cells (BLECs) in Behaviors Relevant to Neurodegenerative Disease.

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This project will aim to explore the role of Brain Lymphatic Endothelial Cells (BLECs) in neurodegenerative disease. Using Zebrafish as the model organism, I will elucidate the function of this novel cell type both in healthy and pathological contexts. Using genetic, chemogenetic, optogenetic and pharmacological manipulations, I will investigate how BLECs respond to perturbations of brain function. As an optically transparent organism, the zebrafish allows for high throughput imaging of BLECs using confocal, 2-photon and super-resolution microscopy after normal and pathological brain activity. I will also assess whether BLECs have a role in shaping behaviors such as sleep by perturbing BLECs and observing changes in behaviour. Since sleep has been linked to metabolic brain clearance, elucidating a role of BLECs in sleep may be of particular relevance to their potential role in neurodegenerative processes. Overall, molecular, cellular and behavioral characterizations of this brain lymphatic cell type may uncover novel pathological mechanisms underlying neurodegeneration as well as lead to the identification of new therapeutic targets.