(4eb) Remembering Kinetics: Studying the Dynamic Protein Activations and Protein Regulations That Form the Molecular Basis of Learning and Memory

In the brain, changes in the strength of synaptic connections underlie our ability to form memories and to learn. These changes in synaptic strength are mediated at the molecular level by dynamic regulation of the spatial location of proteins and by the kinetics of protein-protein interactions. Two classes of transmembrane receptors, G protein coupled receptors (GPCRs) and NMDA receptors, mediate the activation of signal transduction cascades that work in concert to maintain the normal function of our synapses. Disruptions in these signaling pathways almost always lead to disease. All known drugs of abuse mediate their effects via GPCRs and change the dynamics of synaptic response to dopamine in the dopaminergic reward system of the brain. Many proteins involved both GPCR and NMDA signal transduction are disregulated in genetically encoded diseases of the brain, such as depression, schizophrenia, and Alzheimer's.

My research program will be focused on how these signal transduction cascades work together dynamically to control synaptic function and how disregulation of proteins in these pathways can lead to instance of disease. I will apply the tools of chemical engineering, mathematical modeling, molecular biology, and protein biochemistry that I have learned in my Ph.D. and postdoctoral training to perform multi-scale studies of synaptic regulation ? from investigations into protein structure-function relationships, measuring protein binding kinetics and protein activation, modeling signal transduction cascades, to measuring large scale changes in protein regulation in synapses.