BME PhD Preliminary Exam Announcement for Jeffery Coulter (D. Umulis and T. Kim, Co-advisors) Everyone is invited to attend the public presentation beginning at 3:00pm. Title: A computational analysis of CaMKII-actin networks and their influence on dendritic spine morphology Date: December 6, 2024 Time: 3:00 pm Location: MJIS 2001 Committee: Taeyoon Kim (Co-advisor), David Umulis (Co-advisor), Tamara Kinzer-Ursem, Janice Evans Abstract: Dendritic spines are small protrusions on neuronal dendrites responsible for receiving and integrating the post-synaptic signals that contribute to learning and memory formation through a process known as long-term-potentiation (LTP). The changes that occur in spines during LTP can be roughly categorized as “functional" (related to the efficiency of synaptic communication) and “structural" (related to morphological changes). While these changes are closely related and are both required for proper LTP, the molecular mechanisms underlying the structural changes are not well understood. The actin cytoskeleton is the primary system responsible for regulating spine structure and earlier work has found that calcium-calmodulin protein kinase II (CaMKII) has multiple actin binding capabilities. Disruption of CaMKII activity is linked to pathological spine morphologies and improper LTP, although, elucidating how its interactions with the actin cytoskeleton might contribute to this using existing experimental or computational procedures is challenging due to the small size and the multi-scale nature of this system. Here, we plan to test the hypothesis that CaMKII plays a structural role during LTP through its ability to both sequester monomeric G-actin and bundle filamentous F-actin to regulate spine morphology. We will use an agent-based computational model of homogeneous CaMKII-actin networks to understand the relative contributions of CaMKII sequestration and bundling to network architecture. To resolve the limitations of current computational approaches, we will also present a novel hybrid, continuum-discrete modeling framework capable of describing multi-scale biological systems, such as dendritic spines, wherein biochemical reactions are coupled with filamentous networks. Using this framework, we will consider how heterogeneity of CaMKII localization and its activation by calcium (Ca$^{2+}$) following synaptic stimulation affect spine morphology. Our work will provide insight into the structural role that CaMKII plays in LTP, as well as introduce a general computational framework for studying comparable multi-scale systems. -- Bmeroundtable-list mailing list Bmeroundtable-list@ecn.purdue.edu https://engineering.purdue.edu/ECN/mailman/listinfo/bmeroundtable-list