BME PhD Defense Announcement for Catherine Weathered (E. Pienaar, advisor) Everyone is invited to attend the public presentation beginning at 11:00am. Title: Multiscale Spatiotemporal Modeling for Human Disease: Agent Based Models for Nontuberculous Mycobacterium Infections and Alzheimer’s Disease Date: September 30, 2022 Time: 11:00am Location: MJIS 2001 and Zoom https://purdue-edu.zoom.us/j/92267006282?pwd=RVo1Nm82R29OUGovNnlJdVVadkR2Zz0... Advisory Committee: Elsje Pienaar, PhD, Chair Tamara Kinzer-Ursem, PhD Gregory Knipp, PhD Patricio Escalante, MD Abstract: Human disease and the corresponding immune response occur in three-dimensional space and time. Many diseases are difficult to study experimentally, either in vivo or in vitro, due to the complexity of the system. Despite computational models that can address complexity, many do not capture the spatial aspects of disease. Agent-based models are mechanistic, spatiotemporal computational models that can be integrated with other mathematical models to create multiscale models. Here I describe two agent-based models used to examine spatiotemporal progression and possible treatment strategies for two diseases with low treatment success: Mycobacterium avium complex (MAC) infection and Alzheimer’s Disease. MAC are biofilm-forming environmental microbes capable of residing in human lung nodules, causing MAC pulmonary disease (MAC-PD). Clinical drug susceptibility tests and treatment outcomes are poorly correlated, and nodules are complex and difficult to monitor, leading to low MAC cure rates (45-65%). I have developed an informative model of the initial bacterial deposition in the lung airway and the resulting host innate immune response in MAC-PD. After characterizing this model, I use it to probe the effects of biofilms and resulting macrophage signaling or changes in the immune system, such as those during menopause. By building a better understanding of these system dynamics on the progression of infection, I can quantify the impacts of immunological or environmental interventions such as upregulating macrophage killing, reducing cytokines, or reducing frequency of bacterial exposure. Alzheimer’s Disease (AD) is the leading cause of dementia, with no disease-altering pharmacological intervention. Microglia are phagocytotic neuroimmune cells, known to form barriers around plaques. There has been increased interest in leveraging microglia to slow the progression of neurodegeneration by manipulating these barriers. I developed an agent-based model of microglia barriers at the single plaque level and use knock-out experiments to probe the role of microglial mechanisms and quantify their effects on plaque progression. This increased understanding can be used for immunotherapy interventions to slow or prevent the progression of AD.