2015 Winner: Impairment of microtubule motors and their interactions with affiliated proteins leads to disrupted axonal transport in Drosophila motor neurons

Title of Project Impairment of microtubule motors and their interactions with affiliated proteins leads to disrupted axonal transport in Drosophila motor neurons

Division Physical and Biological Sciences

Course or Program Saxton Lab

Description / Abstract Human neurodegenerative diseases are poorly understood. However,
neurodegeneration has been highly correlated to defects in cellular transport mechanisms
in neurons. How do cells organize their components to sustain life and optimize
functions? They use molecular motors that move organelles and other large complexes
into particular positions by dragging them along polarized filament tracks called
microtubules. Kinesin motors typically walk toward the plus-ends of microtubules
(toward the periphery, or anterograde), while dyneins typically walk toward the minusends
(toward the cell center, or retrograde). There are many motor-associated proteins
that connect them to their cargoes and control their motion (on/off/speed etc.). The
functions of motor associated proteins are not well understood. My thesis project
addressed questions about the functions of dynein-associated proteins. Working in
Drosophila, I used RNAi to inhibit the expression of dynein-associated proteins
specifically in motor neurons, then used time-lapse confocal fluorescence microscopy to
look for alterations in the movements of vesicles and mitochondria in the axons of those
neurons. I have found specific influences of dynein-associated factors that point to
organelle-specific mechanisms of linkage and control that are crucial for neuronal
functions.

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