Our laboratory seeks to understand how the circadian clock regulates immune cells using the model organism Drosophila melanogaster. Circadian rhythm, or the oscillation of biological functions over the 24 hour day, is increasingly recognized as an important factor in human health. We found that fly circadian mutants are immunocompromised against bacterial pathogens and that the immunity of wild-type flies oscillates with circadian rhythm: flies have different survival times depending on the time of day that they are infected. Our overarching goal is to understand the molecular mechanisms underlying circadian-regulated physiologies and their roles in immunity against bacterial infection and in neurological disease. The lab is currently focused on three major areas:
Using quantitative live fluorescence imaging in adult flies, we found that specific aspects of immune cell function oscillate with circadian rhythm. This oscillation is lost in circadian mutant flies, including flies defective in circadian clock neurons. We are using fly genetics and fluorescence imaging to identify the signals and pathways underlying this neuroimmune communication from the the nervous system to peripheral immune cells.
Circadian-regulated immunity against bacterial infection
We found that circadian proteins regulate two different types of immunity: resistance and tolerance. Resistance mechanisms increase survival after infection by restricting microbial growth. Tolerance mechanisms increase the organism's ability to tolerate the pathogenic effects of infection. Our goal is to obtain a comprehensive molecular description of circadian-regulated immunity in Drosophila, including both resistance and tolerance mechanisms that together represent the full range of immune responses to infection.
Circadian-regulated immune cells and neurological disease
In many human diseases, patients undergo loss of circadian regulation. How does this impact their immune system function? And does this contribute to progression of disease? We are characterizing circadian regulation of immune cells in several Drosophila models of neurological disease and investigating their roles in susceptibility to infection as well as neurological dysfunction.