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Susan Harbison: The Mystery of Sleep

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Recommended by: Robert Balaban, National Heart, Lung, and Blood Institute

Susan Harbison started out as an aerospace engineer, determining the service life of aircraft parts. But, her interest in genetics was piqued after she got Basenjis, a type of dog, that she entered into dog shows. "Because of my background in engineering, I thought that quantitative genetics might be an interesting place to apply my computational skills," she says.

Harbison began looking into different labs and became interested in Trudy Mackay's lab at North Carolina State University because it focused on how genetic variation and the environment influence complex traits in flies, one of those traits being sleep.

Fly data, she adds, isn't all that different from the structural vibration data she used to deal with. "If you look at the graph [of aircraft vibration data], it's what we call peak-valley data, where you can just plot this on an x-y, and you see these oscillations of data. The [activity count data in] flies [does] the same thing," she says. "It was actually more similar than you might think."

Now at NHLBI, Harbison is following up on a genome-wide association study she performed on a natural population of flies. From that GWAS, she came up with a number of polymorphisms associated with sleep. To determine whether any of these SNPs might be causal, she is conducting artificial selection studies in flies of long and short sleep.

She is also taking flies from the same reference panel and dosing them with drugs to determine how those drugs affect sleep in flies and what gene networks they activate. "We have my baseline genome-wide association with a normal population under standard conditions, and we're going to compare that to what happens when you feed the flies drugs and see if we get the same genetic networks acting across these different environments," she says. "What we want to know is: Are the sleep gene networks robust or are they plastic?"

Paper of note

In 2009, Harbison and her colleagues reported in a Nature Genetics paper on their characterization of sleep in 40 Drosophila lines and performed a GWAS to search for underlying polymorphisms. "A lot of interesting things came out of that paper," she says. "One was that there were many genes potentially involved in sleep. Second, that the genes were conserved across Drosophila species."

Additionally, she and her colleagues found that many of the sleep-associated genes were in related transcriptional modules. "You could see the co-regulation happening," she adds. "If you subtracted basically the expression of one gene, you could see how it perturbed the network and how it affected everything."

Looking ahead

Going forward, Harbison says there will be increased efforts to bring together different types of data into models. "The thing that we are heading toward now is coming up with models that will relate the genetic polymorphisms, the gene expression, and the environment," she says. "We need to try to put all of these things together."

And the Nobel goes to…

While everyone sleeps, why sleep is necessary remains a mystery. If she were to win the Nobel Prize, Harbison would like it to be for solving that long-standing puzzle. "We all know we need to sleep, [and] there's a relationship between short sleep … and obesity and there's also a relationship between poor sleep habits and hypertension and cardiovascular disease," she says. "So, there's fairly widespread impact on human health, but we don't really understand what the impact of sleep is because we don't really understand what the function of sleep is."

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