On a chilly evening last fall, I stared into nothingness out of the floor-to-ceiling windows in my office on the outskirts of Harvard's campus. As a purplish-red sun set, I sat brooding over my dataset on rat brains. I thought of the cold windowless rooms in downtown Boston, home to Harvard's high-performance computing center, where computer servers were holding on to a precious 48 terabytes of my data. I have recorded the 13 trillion numbers in this dataset as part of my Ph.D. experiments, asking how the visual parts of the rat brain respond to movement. Printed on paper, the dataset would fill 116 billion pages, double-spaced. When I recently finished writing the story of my data, the magnum opus fit on fewer than two dozen printed pages. Performing the experiments turned out to be the easy part. I had spent the last year agonizing over the data, observing and asking questions. The answers left out large chunks that did not pertain to the questions, like a map leaves out irrelevant details of a territory.
When asked what's so special about Drosophila melanogaster, or the common fruit fly, Gerry Rubin quickly gets on a roll. Rubin has poked and prodded flies for decades, including as a leader of the effort to sequence their genome. So permit him to count their merits. They have great memories too, he adds. Deprived of their senses, they can find their way around a room--much as you, if you were suddenly blindfolded, could probably escape through whichever door you most recently entered.
Marta Zlatic owns what could be the most tedious film collection ever. In her laboratory at the Janelia Research Campus in Ashburn, Virginia, the neuroscientist has stored more than 20,000 hours of black-and-white video featuring fruit-fly (Drosophila) larvae. The stars of these films are doing mundane maggoty things, such as wriggling and crawling about, but the footage is helping to answer one of the biggest questions in modern neuroscience: how the circuitry of the brain creates behavior. It's a major goal across the field: to work out how neurons wire up, how signals move through the networks and how these signals work together to pilot an animal around, to make decisions or -- in humans -- to express emotions and create consciousness. Even under the most humdrum conditions -- "normal lighting; no sensory cues; they're not hungry", says Zlatic -- her fly larvae can be made to perform 30 different actions, including retracting or turning their heads, or rolling.
We tested most of the 6000 genes in the yeast Saccharomyces cerevisiae for all possible pairwise genetic interactions, identifying nearly 1 million interactions, including 550,000 negative and 350,000 positive interactions, spanning 90% of all yeast genes. Essential genes were network hubs, displaying five times as many interactions as nonessential genes. The set of genetic interactions or the genetic interaction profile for a gene provides a quantitative measure of function, and a global network based on genetic interaction profile similarity revealed a hierarchy of modules reflecting the functional architecture of a cell. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections associated with defects in cell cycle progression or cellular proteostasis. Importantly, the global network illustrates how coherent sets of negative or positive genetic interactions connect protein complex and pathways to map a functional wiring diagram of the cell.