Live imaging and optogenetic control of infections and immune responses in fruit fly larvae

Despite great strides in the quantitative understanding of various components of the immune system, predicting and controlling the behavior of the system as a whole remains a challenge. This challenge is in part due to a lack of tractable in vivo systems that offer precise measurement and control of immune dynamics, such that they are amenable to the theory-experiment dialogue that is a hallmark of physics. To fill this gap, we have been building imaging-based technological platforms in fruit fly larvae. The fly’s minimal yet conserved innate immune system and powerful genetic toolkit make it the “hydrogen atom” of immunology, offering the potential to learn general principles of how spatial interactions and feedback loops in immune signaling and microbial growth steer infection dynamics. I will present our recent experimental successes using light sheet fluorescence microscopy to follow immune response gene expression organism-wide with single-cell resolution and optogenetically inducing viral replication. These tools lay the groundwork for developing predictive, quantitative frameworks that link the collective behavior of many individual immune cells to organism-scale infection outcomes.