Julie A. Williams, PhD
Center for Sleep and Circadian Neurobiology
Translational Research Laboratories
125 S. 31st.
Philadelphia, PA 19104
Tel: (215) 573-1900
Sleep has been proposed to have a role in maintaining a robust immune system. However, the complex relationship between sleep and the immune response is not well understood at either the functional or the molecular level. In an effort to understand the relationship between sleep and immune function, we have exploited the Drosophila genetic model to address questions regarding the reciprocal relationship between sleep and the immune response.
We have established that similar to mammals, fruit flies increase sleep in response to infection or injury. This increase in sleep requires the NFκB transcription factor Relish, which is central to immune signalling in flies. The sleep promoting effect of the immune response is also controlled by the circadian clock such that it is influenced by the time-of-day of immune challenge and is restricted to the morning. Our ongoing studies are aimed at determining the impact of sleep on immune function. We are using genetic and mechanical approaches to manipulate sleep and to evaluate an effect on immune function in terms of survival during bacterial infection and bacterial clearance.
Together, these studies are expected to improve our understanding of how sleep as an adaptive behavior during infection or illness benefits the host. The question of how the immune system and sleep interact has been actively pursued by several investigators for over thirty years. While important discoveries have broadened this field, there remains a need for a strong genetic model. Understanding the reciprocal connection between sleep and the innate immune response will be important for identifying therapeutic strategies for 1) treating infectious illness, especially in drug-resistant cases or in those for which no other treatment is available; 2) treating mood disorders associated with immune dysfunction and sleep disturbances; and 3) treating fatigue associated with aging or with chronic physical illness, such as cancer.
Kuo T-H, Pike DH, Beizaeipour Z, Williams JA. (2010) Sleep triggered by an immune response in Drosophila is regulated by the circadian clock and requires the NFκB Relish. BMC Neurosci 11: 17.
Williams JA, Sathyanarayanan S, Hendricks JC, Sehgal A (2007) Interaction between sleep and the immune response in Drosophila: A role for the NFκB Relish. Sleep 30(4): 389-400.
Hendricks JC, Williams JA, Panckeri K, Kirk D, Tello M, Yin J C-P, Sehgal A (2001) A non-circadian role for cAMP signaling and CREB activity in Drosophila rest homeostasis. Nature Neurosci 4(11): 1108-1115.
Williams JA, Su HS, Bernards A, Field J, Sehgal A (2001) A circadian output in Drosophila mediated by Neurofibromatosis-1 and Ras/MAP kinase. Science 293: 2251-2256.
Hendricks JC, Finn SM, Panckeri KA, Chavkin J, Williams JA, Sehgal A, Pack AI (2000) Rest in Drosophila is a sleep-like state. Neuron 25(1): 129-138.