Nina Tang Sherwood

We use Drosophila melanogaster as a model to understand nervous system development and function. A genetic screen for molecules important to these processes identified the fly ortholog of the spastin gene, which when mutated in humans leads to a progressive neurodegenerative disease called Autosomal-Dominant Hereditary Spastic Paraplegia (AD-HSP). Individuals with AD-HSP have difficulty walking, sometimes from as early as childhood, and can end up confined to wheelchairs. We have shown that loss of spastin in the fly larva compromises motoneuron function, while adults exhibit weak legs and do not fly. Spastin is a member of the AAA family of ATPases, and functions by severing microtubules into smaller segments. Our results indicate that the absence of spastin function in mutant flies leads to a reduction in microtubule content at synaptic boutons, presumably causing the weakened neurotransmission. Among our goals in the lab are to understand how this happens at a cell-biological level, and to examine specific phenotypes associated with mutations mimicking those found in the human disease. Using Drosophila as a model system allows us to rapidly generate flies with any number of specific mutations, and then study the consequences of these mutations at the biochemical, cell biological, developmental, electrophysiological and behavioral levels.