BME PhD Preliminary Exam Announcement for Eugene S. Kim (T. Kinzer-Ursem, advisor) Everyone is invited to attend the public presentation beginning at 10:00 AM. Title: The Role of CaMKIIβ-DrebrinA Binding in F-actin Stabilization in Dendritic Spines. Date: December 20, 2023 Time: 10:00 AM Location: MJIS 1001 Thesis Committee members: Dr. Tamara L. Kinzer-Ursem (Chair) | Dr. Janice P. Evans | Dr. Fang Huang | Dr. Krishna Jayant Abstract: Alzheimer’s disease (AD) is a neurodegenerative disease often observed in elderly patients (≥65y/o). Symptoms of AD include, but are not limited to, loss of learning and memory function and epileptic seizures. Symptoms of AD are rooted in dysfunctional synapses between neurons, leading to impaired synaptic plasticity. Several genes are associated with AD. For example, mutations in the gene encoding drebrin (DBN) are strongly implicated in AD. Drebrin1A (DBN1A) is an actin-stabilizing protein prominently expressed in dendritic spines and helps maintain the cytoskeletal structure. The role of DBN1A in structure-based synaptic plasticity has not been described. Dendritic spines are protrusions on the postsynaptic neuron and are composed of a spine head and spine neck. Although spine head enlargement is commonly seen in synaptic plasticity, an understanding of how the regions between the spine neck, head-neck interface, and spine head are regulated and its relation to synaptic plasticity is lacking. A recent discovery of DBN1A and CaMKIIβ interactions near this interface has been reported. However, it is still unclear how CaMKIIβ-DBN1A increases F-actin bundling in dendritic spines. Based on the literature, we suspect that CaMKIIβ-DBN1A binding plays a significant role in structure-based synaptic plasticity. We hypothesize that during synaptic plasticity, structural remodeling of dendritic spines requires CaMKIIβ-DBN1A to stabilize the F-actin pool at the head-neck interface. To test this hypothesis, we propose to use super-resolution microscopy (SRM) and molecular dynamic (MD) simulations to provide comprehensive evidence that CaMKIIβ-DBN1A complex is critical F-actin bundling during synaptic plasticity in dendritic spines.