702 North Walnut Grove Ave.
Bloomington, IN 47405-2204
Research in the Tracey laboratory aims to understand the general principles that govern the specification and function of neuronal circuits. We study this problem using the fruitfly Drosophila melanogaster, whose relatively simplified nervous system must perform many of the same computations that are carried out by our own. Despite its simplified brain, Drosophila perform an array of complex behaviors. Powerful genetic tools of Drosophila enable the dissection of neural circuits with a precision that is not matched in any other model system. Genetically encoded calcium sensors allow us to measure the neuronal activity of identified consequences of the same activity. Optogenetic tools allow us to activate behaviors via remote control by simply shining light on the animals. Our primary focus is to use the fly model to identify circuits and genes that function in nociception. These studies lead to a greater understanding pain signaling. In addition, we are attempting to identify the molecules that are used in neurosensory mechanotransduction, which underlies our sense of touch. Finally, we are attempting to build trans-synaptic tracers for use in Drosophila. These tools will enable visualization of interconnected circuits in the brain of flies and may eventually be extended to studies in mammals.
Written by: Elisabeth Andrews
In the afternoons of the late 1970s, in the Buffalo suburb of Williamsville, New York, a small boy could be found gazing rapturously into the fish tanks of the local pet shop. Awed and mesmerized, young Dan Tracey was known to spend hours observing and analyzing the fishes' behavior.
"I think I really annoyed the pet store owner with my incessant questions," he recalls.
Fortunately, his inquisitive nature was welcomed by his teachers, particularly his undergraduate mentor at SUNY Buffalo, Carol Berman. Under her guidance, Tracey swapped fish tanks for forests, writing about Berman's work on rhesus macaque monkeys in their natural habitat on the island of Cayo Santiago, Puerto Rico.
As enthralling as he found the monkeys, however, Tracey felt constrained by the limits of field research. "I was dissatisfied with the kinds of experiments you could do studying behavior with the macaques," he explains. "You just didn’t have that much control over the environmental variables."
Seeking a more systematic approach to animal behavior, Tracey turned to genetics. His master's studies took him to Florida National University, he "became enamored with molecular biology," he says.
"I’ll never forget the first time I saw DNA. I was hooked," he recalls. "I remember exactly where I was standing in the lab and who was with me. We put our sample through a procedure, and in the last step we added the ethanol and the DNA precipitated. I could actually see the DNA come out of solution. It was so incredible."
The link between DNA and animal characteristics captivated Tracey. His infatuation with gene expression took him to SUNY Stonybrook for a PhD, where he experimented with Drosophila fruit flies and Xenopus frogs. Towards the end of his program, two events conspired to determine his future research agenda.
One was a tragedy: His grandfather died of lung cancer after months of terrible pain. It struck Tracey as outrageous that the only palliative offered was morphine.
"I was so surprised that we have made almost no progress in pain treatment," he says. "We're still relying on the opium poppy like we have for thousands of years."
The second was a happy occurrence. Tracey met his future wife at Stonybrook, a doctoral student in neuroscience who took him along on her professional retreats. On one such occasion, a professor explained how he measured pain response in rats by placing their tails on metal plates; the plates would be heated until the rats responded by flicking their tails.
"Right away, on our drive back, I started daydreaming about how I could study pain using flies," he says. "As soon as I got home I conducted an experiment where I touched a fly larva with a hot probe and, sure enough, it rolled away from the instrument."
It was the first step of a breakthrough. Tracey knew that if he could find a mutant that did not respond to the probe, he could isolate the fly's gene for pain response. By examining how the gene's expression translated into biological mechanisms, he could uncover new clues to the body's pain pathways.
Tracey tracked down his mutant in the Caltech laboratory of Seymour Benzer, an early genetics pioneer and Tracey's longtime idol. For his postdoctoral research, Tracey worked with his lab mates and a fly mutant they named "Painless" to discover a new type of ion channel that, when activated, could mediate certain types of pain sensation.
Remarkably, an evolutionarily related channel is also found in humans (encoded as a gene known as TRPA1). A similar gene is present in very primitive animals as well - even unicellular organisms - suggesting that this type of pain response has been conserved through billions of years of evolution. In humans, it can be activated by many different types of noxious chemicals, despite those chemicals being structurally unrelated.
"'Painless' taught us a lot about how pain works," Tracey says. “The channel seems to have evolved in very early life as a way to protect against harmful chemicals."
In Tracey's subsequent studies as a faculty member at Duke University, he continued to follow the Painless trail to determine which cells housed the TRPA1 channels. He describes "really beautiful neurons" whose extensive branches enable nociception, the sensory response to potentially harmful stimuli.
Now, as a Gill Chair, Tracey is expanding his Drosophila studies to better understand both nociception and mechanotransduction, the process underlying the sense of touch. By focusing on genes and neurological mechanisms that are also present in humans, his research can both help explain behavior and also pave the way for future innovations in pain treatment.
"It's a long road from a basic science discovery to a new clinical treatment," he cautions, "but it has to start with knowing how these systems work."