BME PhD Defense Announcement for Xiao Liu (E. Pienaar, advisor) Everyone is invited to attend the public presentation beginning at 1:00 PM. Title of the Thesis Research: A DEEP UNDERSTANDING OF EBOLA VIRUS VLP ASSEMBLY: ODE-BASED MODELING APPROACH Date: May 15, 2023 Time: 1:00 PM Place: MJIS 2001 Thesis Committee members: Elsje Pienaar, Nan Kong, Leopold Green, Robert Stahelin Abstract: EBOV infection remains to be a challenge to human health by its high mortality rate. There are only two antibody-based therapy approved today, and the mortality rate is still high. This can be partially due to the fact that study on EBOV is strictly limited to BSL-4 labs, which hinders our understanding of the pathogen. We also lack a systematical and quantitative view of EBOV infection. Mathematical modeling has been used to assist biological and medical studies for a long time, as it has the advantage of integrating data and providing quantitative insight to a biosystem. In our study, we build the primary ODE-based model of EBOV at subcellular level step by step. Through our computation al study, we propose that PS can directly influence the oligomerization process of VP40 filaments and the budding process of VLPs. Also, the oligomerization of VP40 filaments may also follow the nucleation-elongation process. We conduct in-silico simulation to evaluate the efficiency of fendiline in treating EBOV. We find that while in general, fendiline can decrease VLP production, there can be fendiline-induced VLP production at certain time points due to slow filament growth rate or fast VLP budding rate. Also, fendiline is relatively more effective when applied in the budding stage. Moreover, it can be extra efficient when applied with VLP budding step targeted treatment. Finally, we integrate nucleoprotein (NP) into our model. We predict that NP increase VLP production through impacting filament oligomerization and VLP budding steps. Also, dual-effect of NP on VLP production may exist, as too high NP/VP40 production ratio can inversely decrease VLP production. From the aspect of protein expression time, we find that a bit earlier NP production than VP40 production is beneficial for both IB-containing VLPs production and prevention in energy waste on empty VLPs. Overall, we have built a solid foundation towards mathematical EBOV model and demonstrated its ability in assisting experimental EBOV studies.