The challenge was how to disrupt the flies' sleep. Schneider tried building a machine that jostled the flies randomly. "All it was really good at doing was throwing the tubes around the room," said Schneider. "Also it was too regular, the flies got used to it so they could nap."
Another option was to keep the flies in continuous light. But Schneider and Shirasu-Hiza decided that an even better way would be to turn to established fly strains isolated decades ago that possess disruptions in their genes controlling circadian rhythm. In this case, these mutant flies could be kept under exactly the same light and temperature conditions as the normal flies.
They looked at flies that were defective in one of two genes, called "timeless" and "period". They found that the loss of either gene's function made the flies more sensitive to bacterial infections and these sick flies died significantly faster than control flies, which lived two to four times as long as the sick ones.
"We want to know how the internal clock knows the animal is infected, and how does the immune system know that you are not sleeping properly"" said Schneider. "How do those messages get sent back and forth""
Their findings also raise the question of why the flies have a change in their sleep pattern when infected. The researchers speculate that from an evolutionary standpoint, there may be some microbes that are fought better when sleep is disrupted, although clearly not the two microbes they tested in the current study. "We think that is the reason flies do this," said Schneider, "but sometimes it's a good thing, sometimes it's a bad thing."
Building on their findings, they can begin to answer these questions. Shirasu-Hiza will be testing mutant flies with other circadian rhythm genes missing.
Source:Stanford University Medical Center