BME PhD Preliminary Exam Announcement for Barrett Davis (T. Kinzer-Ursem, advisor) Everyone is invited to attend the public presentation beginning at 2:00 pm. Title: A Structured Approach to Developing Mechanistic Models of Biological Systems Interactions across Scales Date: May 2nd, 2025 Time: 2:00 pm Location: MJIS 2001 and Zoom Zoom Link: https://purdue-edu.zoom.us/j/93692421121?pwd=6DswLzRxWgQCbFuhzkqxERTIWle5It.1<https://nam04.safelinks.protection.outlook.com/?url=https%3A%2F%2Fpurdue-edu.zoom.us%2Fj%2F93692421121%3Fpwd%3D6DswLzRxWgQCbFuhzkqxERTIWle5It.1&data=05%7C02%7Cbmeroundtable-list%40ecn.purdue.edu%7C4091a03e20d1482f199a08dd80d7666b%7C4130bd397c53419cb1e58758d6d63f21%7C0%7C0%7C638808384795187696%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=HwEjSf99nTnRZNLLmU1aOqwlt%2F0PsJz1KkDK9guC9Wo%3D&reserved=0> Meeting ID: 936 9242 1121 Passcode: twobricks Committee: Dr. Tamara Kinzer-Ursem (chair), Dr. Elsje Pienaar, Dr. Luis Solorio, Dr. Kevin Webb Abstract: Mechanistic computational models provide a quantitative means to study complex systems interactions within a theory-based framework not otherwise afforded by similar, statistical approaches. However, challenges to model construction, especially the sparsity of parameter data relative to the density of biochemical interaction networks, limits the predictive power and ready application of these models to clinical research. In response to this, here I propose an approach to characterizing biological system interactions from atoms to action potentials in two aims. The first aim details a new method for the cleanroom-free manufacture of an optical biosensing platform to measure the label-free interaction kinetics of single molecules in free-solution. Accompanying this, I develop a biophysical model to interpret this platform's experimental results, including association and dissociation rates, as well as the translational and rotational diffusivities of individual molecules. In the second aim, I create a compartmental model to simulate differences in the activity-dependent synaptic plasticity of typical, excitatory hippocampal neurons and those with SYNGAP1 haploinsufficiency (SG+/-), a rare neurodevelopmental disorder. Simulated small molecule and genetic therapies alike are explored for their potential to recapitulate typical synaptic plasticity in the SG+/- system. Global sensitivity analyses are used to quantify first, second and total-order interaction sensitivities of the plasticity model and to rationally prioritize any future parameterization efforts. Together these studies provide an approach to efficiently parameterize biochemical models and to trial new therapeutics in silico, with immediate applications for both historically understudied rare diseases and basic biomedical sciences more broadly. -- Bmeroundtable-list mailing list Bmeroundtable-list@ecn.purdue.edu https://engineering.purdue.edu/ECN/mailman/listinfo/bmeroundtable-list