The Baenziger lab is focused on molecular neuroscience. The human brain contains roughly 100 billion (1011) neurons and 100 trillion (1014) synaptic connections, with tremendous biochemical complexity at each synapse. Synapses are not simple on/off switches, conducting signals from one neuron to another. They can be thought of as tunable switches; with subtle modifications in the strengths of these synaptic communications being essential to higher brain functions.
We study the structure, folding, cell-surface trafficking, and ultimately function of a superfamily of proteins, called pentameric ligand-gated ion channels (pLGICs), that play a central role in synaptic communication. This superfamily includes fast-acting neurotransmitter receptors that respond to acetylcholine, glycine, g‑aminobutyric acid (GABA), and 5-hydroxytryptamine (serotonin), etc. These receptors have been implicated in a variety of neurological processes and diseases, and are targets of numerous pharmaceuticals. Recent structural information is beginning to shed light on the molecular basis of pLGIC function.
Our lab is particularly interested in the role played by membrane lipids in modulating pLGIC function. Most of our research is focused on the prototypic member of the pLGIC superfamily – the nicotinic acetylcholine receptor (nAChR). The activity of the nAChR is exquisitely sensitive to its lipid environment. Even subtle changes in lipid-protein interactions can have profound effects on nAChR-mediated synaptic communication, with significant physiological consequences. Fundamental knowledge of how the nAChR and other pLGICs respond to changes in their lipid environments during both normal and abnormal brain function may prove important for understanding the mechanisms underlying the altered synaptic communication that occurs during the course of human disease. Through biophysical and functional studies of site-directed nAChR mutants, as well as its prokaryotic homologs ELIC and GLIC, we explore the mechanisms underlying lipid-dependent nAChR modulation, and its role in synaptic function.
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