BME Master's Defense Announcement for Benjamin Dahl (T. Kinzer-Ursem, advisor)

Everyone is invited to attend the public presentation beginning at 8:00am.

Title: Fundamental and applied modeling in neurology: post-synaptic kinase anchoring and DNA amplification assays.

Date: Thursday, November 30

Time: 8:00am

Location: BRK 1001

Committee members: Dr. Tamara Kinzer-Ursem (chair), Dr. Elsje Pienaar, and Dr. Scott Bolton

Abstract: Computational modeling has a broad range of applications in neuroscience, from discovering fundamental attributes of neuronal synaptic function to helping develop tools to fight neurodegenerative disorders. Here, we utilize computational modeling to investigate the dynamics of receptor phosphorylation that are important in regulating dynamic changes in synaptic strength. Within synapses, a thick network of proteins makes up a membrane-less structure called the post-synaptic density (PSD) in post-synaptic dendritic spines. The increased number and phosphorylation of glutamate receptors within the PSD is a hallmark of increased synaptic strength. A-kinase anchoring proteins (AKAPs) are important scaffolding proteins in the PSD that have been established to localize a number of regulatory enzymes such as protein kinase A, calcineurin, and phosphodiesterases near the cell membrane and glutamate receptor tails. However, it is still unclear what is their overall effect on glutamate receptor phosphorylation and trafficking. Here, a spatial stochastic computational model of AKAP and enzymatic binding partners in the PSD is developed and the dynamics of the system analyzed. Model results demonstrate the correlation between glutamate receptor tail phosphorylation and AKAP localization. By computational “knockdown” of AKAPs we are able to quantify their effect on glutamate receptor phosphorylation, investigate the role of spatial localization, and posit their potential impacts on LTP and synaptic plasticity.