Amanda Hussey

Abstract:

My research in the Chambers lab has focused on exploring the mechanisms which underlie memory formation by using minimally invasive, ligand-directed chemical probes. Our lab has developed a novel method for the delivery of cargo to endogenous proteins which are being used for neuronal receptor labeling. The first generation probe demonstrated the feasibility of using this ligand-directed fluorophore connected via a photolabile linker. We labeled glutamate receptors on hippocampal neurons and observed their locations and movements, thus opening the lab to a myriad of potential targets for the use of these probes.

The research I that have more recently initiated expands the initial study and application of the probe strategy to further characterize glutamate receptors. I am also following up on observations that we made using our first generation probe. For instance, we found an abundance of this specific phenotype of receptors on certain cells and we also found them to be rapidly recycled. These effects could be blocked pharmacologically suggesting that the probe is specific for these receptors. Alternatively, the pharmacophore that our first probe is based on could be much more promiscuous than is presently appreciated in the field of neurobiology. Thus, we have designed a new probe to allow for the covalent modifications and affinity purification of endogenous receptors. Purified proteins will be subject to SDS-PAGE analysis and proteomic identification.

The use of this new proteomic probe will aid in our understanding of the molecular mechanisms that underlie memory formation and potentially provide insight into neurodegeneration.