The 2017 Nobel Prize in Physiology or Medicine was awarded Oct. 2 to three scientists for research on the body's internal clock, or "circadian rhythm."
Starting in the 1980s, Jeffrey Hall, Michael Rosbash and Michael Young isolated a gene in fruit flies, or Drosophila melanogaster, that controlled a protein's daily creation and destruction. By studying the molecules that regulate this gene, the team identified the genetic mechanisms of the circadian clock.
Indiana University is widely regarded as a leader in the support of research of the type that led to the 2017 Nobel discovery due to three world-class, federally funded facilities that support the use of fruit flies in genetic study: the Drosophila Stock Center, the Drosophila Genomics Resource Center and FlyBase.
"Although the last common ancestor of flies and humans existed over 600 million years ago, flies and humans are very similar on a genetic level," said Dan Tracey, an associate professor in the IU Bloomington College of Arts and Sciences' Department of Biology, whose lab has isolated 36 genes involved in pain sensitivity using fruit flies. "The primordial creature whose descendants evolved into flies and humans had many of the same organs as us -- a nervous system and some means to detect external stimuli, for example. This means that studying simpler forms of life often tells us how the same genes work in people."
These "evolutionarily conserved genes," whose essential function has unchanged over time, exist because once evolution finds solutions to fundamental problems -- the absorption of nutrients in the environment or the elimination of waste from the cell, for example -- the process tends not to change unnecessarily. As a result, many key genetic sequences are found across the tree of life. Approximately 70 percent of the human genes associated with disease are also found in the fruit fly.
"With three critical National Institutes of Health-funded centers that support Drosophila research globally, IU Bloomington is the 'mecca' of the Drosophila world," said Andrew Zelhof, an associate professor in the IU Bloomington College of Arts and Sciences' Department of Biology and director of the Drosophila Genomics Resource Center. "The success of Drosophila research as a field has been partly due to the dedicated efforts of these resource centers to provide Drosophila researchers with equal access to information and resources."
Established in 1987, the Drosophila Stock Center currently maintains 63,000 genetically different fruit fly strains with mutations for studying various diseases or biological pathways in fields such as genetics, molecular biology, cell biology and developmental biology. These strains can also be shipped to researchers across the globe, with about 217,000 living fruit fly samples distributed in 2016 alone. Located on the fifth floor of Jordan Hall on the IU Bloomington campus, the center employs over 60 people. The co-director of the Drosophila Stock Center is Thomas Kaufman, IU Distinguished Professor in the Department of Biology.
More recently, IU established the Drosophila Genomics Resource Center with $2.7 million from the NIH in 2003. Working closely with the Drosophila Stock Center, the Drosophila Genomics Resource Center provides the research community with broader access to genomics resources on fruit flies by acquiring, archiving, curating and distributing these essential genetic tools. The center also supports improved research protocols on fruit fly research; provides email and telephone support; and engages in outreach at national conferences. The center's grant was most recently renewed in 2013 with $3.2 million from the NIH.
IU's third internationally recognized Drosophila resource is FlyBase, the most comprehensive database of fruit fly DNA sequence information in the world. The database was created 25 years ago and is currently funded by $20 million from the NIH, $3 million of which goes to IU Bloomington. The FlyBase consortium includes Harvard University, and Cambridge University in the U.K. Kaufman is director of the IU FlyBase facility.
It's estimated that IU hosts at least eight labs in the Department of Biology that rely upon the tools and genetically tailored fruit flies of these three research centers. These include the labs of Brian Calvi, a professor who studies DNA replication; Justin Kumar, a professor who studies eye development; and Nicholas Sokol, an associate professor who studies microRNA. Others include professor Richard Hardy and assistant professor Irene Newton, who study the blockage of virus transmission in insects infected with Wolbachia bacteria; assistant professor Jason Tennessen, who studies similarities between early cellular growth in fruit flies and cancer; and Zelhof, who also studies eye development in fruit flies to advance genetic treatments for eye disease in people.
"IU is truly the center of the Drosophila universe," Newton said. "We use lots of fly resources, and they are phenomenal. This year's Nobel is really a celebration of basic research and how studying genetically conserved biological mechanisms in Drosophila -- including the circadian clock -- can teach us a lot about our own biology."
This year's award is also the fifth Nobel Prize in Physiology or Medicine to recognize research on Drosophila, starting with the original prize in 1933 to Thomas Hunt Morgan, who used flies to reveal how physical traits are passed down through generations, and the second prize in 1934 to Hermann Muller, who discovered that X-rays induce mutations in flies. The other prizes for research on Drosophila were the 1995 prize for the identification of genes controlling basic developmental processes and the 2011 prize on inherited versus acquired immunity.