BME PhD Prospectus Defense - Noshin Nawar

Title: “Quantifying Heterogeneity in the Drosophila melanogaster NF-KB Imd Pathway of Innate Immunity with Live Imaging of Fluorescent Reporters”

Advisory Committee: John Ngo, PhD – BU BME (Chair) Zeba Wunderlich, PhD – BU Biology (Advisor) Alex Green, PhD – BU BME Thomas Gilmore, PhD – BU Biology

Abstract: Evolutionarily conserved innate immune pathways detect pathogen challenges and regulate downstream behaviors that determine animal survival. However, it is still unclear how pathway elements work in concert to produce quantitatively heterogeneous responses to varying stimuli. Drosophila melanogaster is a widely used model organism for studying innate immunity due to its conservation of key signaling pathways. The Drosophila Imd response, homologous to mammalian TNF, detects Gram-negative bacteria and activates transcription of key antimicrobial peptides via the NF-KB transcription factor, Relish. A host of regulatory factors tune dynamics along different points of the pathway, but their individual contributions are difficult to control or quantify. Thus, in this project, I will treat the Imd pathway of immune responsive S2* cells as a black box, inputting dynamic stimuli via a microfluidic chip and measuring downstream Relish and transcriptional dynamics using live fluorescent reporters. I will then apply classical signal processing techniques on these input-output relationships to dissect the Imd black box and characterize the archetypes contributing to its heterogeneity. Success in this project will enhance our understanding of how innate pathway dynamics discriminate input signals and respond with fine-tuned regulation optimizing host survival.