BME PhD Preliminary Exam announcement for Derrick Dankwa (L. Green, advisor) Everyone is invited to attend the public presentation beginning at 11:00 am. Title: An in-silico Study on the Design of a Biological Controller for Regulating Sepsis induced macrophage Paralysis Date: October 2nd, 2024 Time: 11:00 am Location: MRGN 206 or Zoom: https://purdue-edu.zoom.us/j/2977861198<https://nam04.safelinks.protection.outlook.com/?url=https%3A%2F%2Fpurdue-edu.zoom.us%2Fj%2F2977861198&data=05%7C02%7Cbmeroundtable-list%40ecn.purdue.edu%7Cc3329099adc74753451b08dcd811d592%7C4130bd397c53419cb1e58758d6d63f21%7C0%7C0%7C638622818309820016%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=gZISernaWs%2Fg3Wj8ShzhwkNkx05SXuG4r8JZ3obq8Gw%3D&reserved=0> Committee members: Leopold Green, (chair), Elsje Pienaar, Yoon Yeo, Choi, Jong Hyun Abstract: Macrophages play key roles in both the progression and resolution of inflammation. Their functional plasticity is characterized by polarization into either the pro-inflammatory M1 phenotype or the anti-inflammatory M2 phenotype as well as occupying a position along the continuum between these two extremes. In sepsis, dysregulation of this phenotypic switch (macrophage paralysis) interferes with the proper influx and removal of immune cells, decreasing the efficiency of pathogen clearance and amplifying tissue necrosis. Irrespective of the advancements in understanding the immune response and developing therapeutics to manage the disorder, significant challenges remain in achieving optimal clinical outcomes. Emerging studies suggest modulating macrophage phenotypes and signaling pathways as a novel therapeutic approach to restore immune homeostasis in dysfunctional inflammatory states. In response to this, we propose to inform the design of a novel class of theragnostics that target the dysregulated signaling dynamics to positively regulate the outcomes of the disorder. We will abstract the immune response into the language of mathematical modeling and feedback control,(a mathematical framework traditionally used in engineering to manage dynamic systems) to develop a biologically feasible controller as gene circuits capable of sensing and responding to immune signaling dynamics in real time as a multipronged therapy for sepsis. To achieve this, the following aims would be explored. Aim 1: Design an insilico framework to regulate macrophage paralysis via controlled IL-6 expression. Aim 2: Parameterize and control the spatio-temporal immune cell and signaling dynamics using a lung-on-a-chip system. Overall, our proposed study aims to bridge the gap between theoretical modeling and practical application in the treatment of sepsis. By developing a novel approach that combines advanced mathematical modeling with cutting-edge biotechnology, we seek to inform the design of a novel class of effective therapeutic strategies to combat this serious condition. Our approach has the potential to significantly advance the development of next generation gene and cell-based immunotherapies for inflammatory disorders. -- Bmeroundtable-list mailing list Bmeroundtable-list@ecn.purdue.edu https://engineering.purdue.edu/ECN/mailman/listinfo/bmeroundtable-list