Collaborative Research: OSIB: Uncovering drivers of infection resistance, survival, and tolerance using non-invasive real-time imaging

About This Grant

Individuals can vary greatly in their response to the same infection. This variation can be caused by many factors, including genetics, life experiences, and environmental conditions. By using fruit flies (Drosophila) as a model, researchers can control for many of these factors, allowing them to focus on the roles of genetics and other factors in infection outcomes. However, due to technical limitations, traditional infection studies typically rely on measurements of the infection progression at a single time point, making it difficult to track the infection’s dynamic progression in an individual over time. This project aims to solve that problem by developing new light-based tools to monitor infections in living animals. By using glowing bacteria and glowing proteins that show an animal’s immune response, researchers will measure both bacterial growth and the host’s immune response in individual flies. This will allow them to identify genetic and other factors that influence infection outcomes in different animals. This research will introduce new biotechnology i.e., innovative imaging techniques, that will contribute to the bioeconomy and could reshape our understanding of disease progression, potentially revealing immune genes conserved across species. The project also provides hands-on training for students and postdoctoral researchers in genetics, computational modeling, and imaging. Additionally, the team will create educational materials and outreach programs to inspire the next generation of American scientists. By advancing both research and education, this work has the potential to improve our ability to predict, understand, and ultimately control infections. This research aims to uncover genetic and stochastic factors that influence infection survival by tracking microbial dynamics and host responses in individual animals. Using the Drosophila model system, researchers will develop bioluminescence imaging (BLI) tools for real-time, longitudinal monitoring of infection. This approach will allow direct observation of infection progression and help identify novel immune genes. The project has two main goals. Goal 1: Uncover the genetic drivers of infection resistance, tolerance, and outcome. Different fly genotypes show significant variation in survival, but infection resistance at a single time point does not always predict survival. This may be because immune responses unfold over time and immune tolerance mechanisms also influence survival. By monitoring infection dynamics in genetically diverse individuals, researchers aim to identify genetic factors that affect resistance, tolerance, and overall survival. Goal 2: Uncover the stochastic contributions to infection outcome. Current technologies do not allow observation of microbial growth dynamics and host responses in a single animal. To address this void, researchers will develop orthogonal luciferase-luciferin pairs that report on microbial load and host gene expression. A simple model of bacterial growth and host response will be compared to those with more complex dynamics, including feedback and fluctuations, to find which fit the data best. Such work will reveal the role of fluctuations in microbial growth and host response to infection outcome, providing potentially novel strategies for infection control. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.