Description of Research Expertise

Excess sleep and fatigue are commonly experienced during infectious illness in humans. Increased sleep associated with infection has also been documented in a wide range of animals, including Drosophila. It has therefore been proposed that sleep is an adaptive response to infection and has a role in fighting infection. Sleep disturbance and inflammation are also associated with a number of human diseases, including cancer, cardiovascular, metabolic, and depressive disorders. These findings underscore the importance of the relationship between sleep and the innate immune system in sustaining human health. However, the molecular mechanisms of excess sleep and fatigue during illness and its relationship to clinical outcome remain poorly understood.

The research that I direct is focused on identifying mechanisms of restorative sleep, as well as how sleep disintegrates during illness. We have found that acute stress produced by bacterial infection, aseptic injury, and heat shock all induced a transient increase in sleep in fruit flies. Although sleep increases with acute stress, during chronic stress, such as a later stage of infection, the quality of sleep declines. It becomes progressively more fragmented as indicated by shorter and more frequent sleep bouts, similar to that in aged flies. We have shown that enhancing sleep both before and after infection promoted survival. The restorative properties of sleep are not well understood, and the mechanisms by which sleep disintegrates during infection are unknown. Thus specific questions addressed are 1) what are the mechanisms of stress/infection-induced sleep; 2) why does the acute restorative sleep response that occurs with infection not persist but turns into poor quality fragmented sleep over the course of the infection; and 3) how can this poor quality sleep be ameliorated to promote recovery? My approach to addressing these questions is to exploit the Drosophila genetic model to evaluate mechanisms by which a cellular stress response promotes sleep and how chronic stress, such as infection, suppresses sleep. We also plan to investigate the neuronal circuitry that is involved in mediating these responses.