It's a long-term commitment to find genetic ways to both trigger and track fly behavior.
Optogenetics is a popular approach in neurobiology, but there's a catch. Light precisely targets and manipulates the chemical or electrical signals in a set of neurons that express a light-sensitive ion channel. But when neurobiologists use optogenetics to study vision and neuronal processing in fruit flies, as does Andrew Straw at the Research Institute of Molecular Pathology (IMP) in Vienna, the experiment is quickly ruined. Any attempt to illuminate neurons invariably sheds light on the fly retina.
To address this drawback, Straw and his colleagues have built what they call a fly mind-altering device, FlyMAD, which uses heat instead of light to manipulate neurons. “We can turn on—and that was one important thing—we can turn off neurons,” says Straw. Silencing specific motor neurons turns a fly's fast scramble captured on video into slow, hesitant steps. Activating other neurons leads the fly to scurry backwards. Turning on a courtship neuron triggers behavior that is best watched with parental supervision.
Commenting on Straw's work, Alexander Borst, who directs the Max Planck Institute of Neurobiology, says, “it's truly amazing what you can do these days with fly genetics, a laser, some optics, a computer—and Andy, who puts it all to work.”
You want to understand an animal within its natural context.
As Straw explains, “you want to understand an animal within its natural context”—outside on a sunny day, for example. An alternative is to use experimental techniques that cause the least perturbation and have the benefit of targeting specific neurons to observe the behaviors they trigger in a controlled and repeatable fashion.
Straw admits FlyMAD's experimental setup is technically complex: it includes an infrared laser, a visible-light laser, two cameras and an algorithm that tracks multiple flies simultaneously and feeds back images to control the positioning of the laser. A biologist might need help calibrating the system that captures the fly's movements, pinpoints the pixel corresponding to the fly's position and sends the signal to the galvanometer mirror to point the laser in that direction. But he hopes that labs without extensive technical expertise can use the system; “all the details associated with making it work—they're done,” says Straw.
As a student Straw was drawn to neuroscience and computer programming and realized he could apply real-time interactive computing techniques in experiments. Straw was trained as a neuroscientist, and completed his PhD at the University of Adelaide in Australia. He was a postdoctoral fellow in Michael Dickinson's lab at the California Institute of Technology (Caltech) and also held a non-tenure-track research faculty position there.
Three years ago, as he was applying for professorships, he took a transatlantic leap and landed his current position in Austria. “It is pretty rare that Americans move to Europe,” he says. As an undergraduate, Straw spent a year in Scotland, where he also met his future wife.
Straw likes the IMP's research atmosphere and resources, and he has also received a grant from the European Research Council. He feels at home in Europe's scientific community and is also happy to be close to mountains. Growing up in the western United States, Straw loved the outdoors and “wild spaces.” Full-day fun for him, he says, is climbing a mountain from pitch to pitch, or from one anchored location to the next. “I would love to get back to the mountains a little bit more.”
Straw's research projects, too, are extended 'climbs' requiring long-term commitment. Making the technology robust and reliable is not a quick affair. It takes courage to embark on such projects, which offer no guarantee of success. “I wouldn't say I was brave, maybe I was just naïve,” he says. Both Caltech and the IMP have given him the freedom to take this approach, he says.
Straw meets young scientists who want to “fledge really early” and who want faculty positions after short postdoctoral fellowships. “I'm not sure I would advise that at all,” he says. From day one, a faculty job requires grant-writing experience and ideas for graduate student projects, which have to be launched before a lab is up and running.
Instead, he recommends taking a long view. Even if a post is not the “ideal long-term position,” researchers early in their careers will want to take the time to first build their vision and repertoire. “To me it would make a lot of sense to stay with that,” says Straw, “until you are really ready to fly on your own.”
Bath, D.E. et al. FlyMAD: rapid thermogenetic control of neuronal activity in freely walking Drosophila. Nat. Methods 11, 756–762 (2014).
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Marx, V. Andrew Straw. Nat Methods 11, 697 (2014). https://doi.org/10.1038/nmeth.3003