Our laboratory seeks to understand how the circadian clock regulates behaviors, physiologies, and metabolism 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. Our overarching goal is to understand the molecular mechanisms that connect the circadian clock to these behavioral, metabolic, and immunological outputs. We also aim to determine how these connections are perturbed in the context of disease states such as aging. The lab is currently focused on three major areas:
Circadian-regulated immunity against bacterial infection
We found that circadian proteins regulate two different types of immunity in response to bacterial pathogens: 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.
The relationship between sleep and oxidative stress
Circadian rhythms play a central role in sleep/wake cycles. Sleep is an evolutionarily conserved behavior throughout the animal kingdom, but its functions are not entirely understood. Chronic sleep deprivation is associated with the development of neurological, metabolic, and cardiovascular diseases, asserting sleep’s essential role in promoting health. We found that short-sleeping fly mutants exhibit sensitivity to acute oxidative stress, having a shorter survival time than controls. Long-sleeping flies show resistance to acute oxidative stress, surviving longer than controls. We aim to understand the molecular mechanism through which sleep defends against oxidative stress. Since sleep quality declines with age, we are also interested in how sleep’s role as an antioxidant changes with age and contributes to the development of age-related diseases.
Circadian-regulated metabolism
The timing of metabolic processes is central to our health and longevity. Many metabolic pathways, involving proteins, lipids, carbohydrates, and nucleic acids, have been shown to be regulated by the circadian clock. Our lab has observed distinct metabolic differences in circadian fly mutants as compared to controls. Our goal is to understand what aspects of circadian-regulated metabolism impact our health and lifespan. How does the clock temporally sync these metabolic processes across different tissues in the body? What circadian-regulated behaviors may beneficially or detrimentally impact metabolism? How does circadian-regulated metabolism change with age, leading to the development of metabolic disease?