| My primary research interest is in using the model organism Drosophila to understand the molecular basis for neurodegenerative diseases, such as Parkinson’s and Alzheimer’s diseases, and developing suitable disease-modifying therapies. Together these two diseases represent the most common neurodegenerative disorders. Previously, I have used Drosophila to interrogate the role of cytosolic dopamine in mediating cellular toxicity, and found that sequestering intracellular dopamine may be a viable mechanism for preventing the loss of dopamine neurons seen in Parkinson’s disease. Currently, I am investigating the biological role of the vesicular acetylcholine transporter in mediating the release of acetylcholine. Although there is a wealth of knowledge on the role of ACh receptors in cholinergic neurotransmission, the role of presynaptic acetylcholine release in mediating synaptic physiology and behavior is not well understood. Specifically, I am interested in determining how graded changes in ACh release modulate synaptic activity and downstream behaviors. To study this question, I am using an allelic series of point mutants in the Drosophila VAChT, the protein that packages and transports ACh for synaptic release. These alleles range from mild to severe, and allow me to determine the relationship between graded changes in acetylcholine release and deficits in acetylcholine-mediated behaviors such as locomotion. Owning to its strength as a genetic work horse, Drosophila melanogaster presents an excellent model system to study the molecular basis of cholinergic neurotransmission. The significance of this work is underscored by the fact that even though cholinergic neurons are disproportionately affected in AD, the underlying cause of this differential susceptibility is not known. This research therefore has the potential to uncover factors that render cholinergic neurons vulnerable to AD. |
