W. Dan Tracey, Linda and Jack Gill Chair of Neuroscience and Professor in the College of Arts and Sciences' Department of Biology at Indiana University Bloomington, studies nociception—the sensory mechanism that allows animals to sense and avoid potentially tissue-damaging stimuli. The ability to detect pain is critical for survival across species.
Tracey has been funded $1,906,629 through a Maximizing Investigators' Research Award for Established Investigators (R35). The MIRA, as the award is known, is presented by the National Institute of General Medical Sciences (NIGMS), a section of the National Institutes of Health. The MIRA provides researchers with greater stability and flexibility which in turn enhances scientific productivity and the chances for important breakthroughs. The award is for five years.
The MIRA awarded to Tracey replaces his earlier 10-year NIGMS project-based R01 grant.
Under the R01, Tracey and members of his lab discovered 275 genes that showed high expression in the pain sensing neurons when compared to other sensory neurons by using laser capture microdissection to isolate RNA from the pain sensing neurons of fruit fly (Drosophila melanogaster) larvae. Drosophila melanogaster is a key "model organism" used in biomedical research due to the genetic similarity of flies and humans, which share close to 10,000 genes. Over the years, scientists have learned how human and other organisms' genes function by conducting research with Drosophila.
The Tracey lab then tested the function of the 275 genes by knocking them down with RNAi and testing the effects of this loss of function in behavioral response to nociception. This led them to 36 genes that have roles in causing hypersensitivity or insensitivity in the pain sensing neurons.
The MIRA will let the Tracey lab broaden its research to understand what each of the genes does in nociceptors. Nociceptors are specialized neurons that detect and respond to potentially damaging factors through the expression of molecules that function to detect and signal the presence of potential harm.
The lab's primary focus has been the study of nociception; however, Tracey and members of his lab have also explored mechanisms underlying the sense of gentle touch, and most recently, the sense of proprioception—the perception or awareness of the position and movement of the body. They have found that each of these senses relies on specific classes of non-ciliated multidendritic sensory neurons.
"The multidendritic neurons that are dedicated to a specific sensory modality are morphologically distinct from one another, and they have diverse patterns of gene expression," said Tracey. "We seek to define how these distinct morphologies relate to function as well as how ensembles of genes expressed within the distinct morphological types of neurons control sensory pathways of somatosensation with a primary focus on nociception."
Tracey's research program strives to understand the molecular, cellular, and circuit mechanisms underlying nociception. Over the next five years, the lab members' primary goal will be to further characterize the function of the nociception genes they have identified.
"Our focus is on evolutionarily conserved genes not already understood to have important roles in nociception," Tracey noted. "These studies provide the greatest impact in creating new knowledge."
Additionally, Tracey hopes their research will begin to shed some light on the neuronal network for nociception behavior as other ongoing studies in the lab have characterized the motor outputs of the escape behavior. These studies will leverage a nearly completed “connectome” (or wiring diagram) of the larval brain.
"We hope that our work will contribute to the basic mechanistic understanding of the molecular mechanisms of nociception, eventually contributing to better treatments for pain," Tracey concluded.
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