Research Projects

The proposal aims to study the physiological and metabolic roles of intracellular neurotransmitter transporters, which are crucial in filling synaptic vesicles with biogenic amines and inhibitory neurotransmitters, facilitating chemical neurotransmission across neural synapses. These transporters are structurally, mechanistically, and pharmacologically distinct from plasma membrane neurotransmitter transporters (SLC6) involved in Na+-coupled symport of neurotransmitters at the neural synapse. Lowered expression or dysfunctional mutants in vesicular transporters can lead to neurophysiological disorders. The vesicular monoamine and inhibitory amino acid transporters are poorly studied compared to SLC6 members. The study aims to study the architecture and dynamics of these transporters in their multiple conformational states using electron cryomicroscopy (cryoEM). Novel strategies to enhance the size of the transporters using fusion proteins and single-domain antibodies targeting vesicular transporters will be employed. The proposal also aims to study the role of congenital mutants on the conformational heterogeneity of VMATS, which confer Parkinson's Disease-like conditions in afflicted patients. Additionally, single-domain camelid antibodies against vesicular transporters will be generated for use as fiducial markers in cryoEM image processing and as potential intracellular imaging tools to study and track intracellular localization of vesicular neurotransmitters in neurons.