RESEARCH
In vivo control mechanisms of cargo motility within axons:
Motor activities are highly regulated in vivo. We use Drosophila genetics, in vivo imaging and computational analysis to identify the mechanisms of cargo motility within larval axons.
Movie1: Movement of APP-YFP within a single larval axon
Movie2: Movement of APP-YFP is directed by expression of pathogenic polyQ proteins within a single larval axon
Moving huntingtin-cargo complexes:
Huntingtin differentially affects the motility dynamics of specific Rab-containing vesicles. We use Drosophila genetics, simultaneous in vivo imaging, computational analysis and biochemical strategies to isolate specific huntingtin-Rab-vesicles.
movie: Huntingtin-GFP and Rab4-mRFP co-migrate in vivo, but Rab4-mRFP and APP-YFP do not.
Axonal transport defects and neurodegeneration:
Axonal transport defects are seen in many neurodegenerative diseases such as Alzheimer’s disease, Huntington’s disease, Parkinson’s disease much earlier than any behavioral defects, neuropathology or cell death. We use Drosophila models of neurodegenerative diseases coupled with differentiated neurons from iPSCs from human disease patients to test how the axonal transport pathway contributes to neurodegeneration.
Nanoparticles as potential therapeutic vesicles to modify axonal transport defects:
We are exploring the potential use of a novel nanoparticle as a therapeutic vesicle for directed targeting to neurons.