image: Montana State University researcher Dana Rashid, received a $1 million award from the W.M. Keck Foundation to continue research into the connections between inflammation and skeletal development. The work began through explorations into dinosaur evolution into modern birds.
Credit: MSU photo by Marcus "Doc" Cravens
BOZEMAN — The project began as an effort to re-engineer ancestral dinosaur traits in modern birds.
Dana Rashid, an assistant research professor in Montana State University’s Department of Microbiology and Cell Biology, had collaborated with the Museum of the Rockies to explore how the tails of modern birds evolved from those of their prehistoric predecessors. But her research revealed a strange phenomenon: Inflammation, similar to that which occurs when a body is healing a broken bone, was present in the fusion of avian dinosaur bones into their modern tails, even though no broken bones were present.
That discovery led to more exploration of where this inflammation was coming from and whether it was somehow important to avian skeletal development. It turned out that it was, a finding that was published in the journal PNAS last year. Now, Rashid has been awarded a prestigious $1 million grant from the W.M. Keck Foundation to continue studying the phenomenon, which has implications for health and skeletal development in humans.
“It was just a complete shock,” said Rashid of the announcement that the project had been selected by the Keck Foundation. “Our project is out-of-the-box. It's unconventional, and this is phenomenal for us. It's huge in so many ways.”
Along with collaborators Susan Chapman at Clemson University and Kim Cooper at the University of California, San Diego, Rashid will continue to explore the role that inflammation plays in skeletal development.
In their earlier work, the researchers discovered that when chickens were treated with anti-inflammatory drugs, the evolutionarily derived bone fusion was halted—an astounding impact for a drug to have on an evolutionary mechanism developed over hundreds of millions of years. If similar responses were to be observed in humans, Rashid said, they could raise questions about the impact of corticosteroids or other anti-inflammatories on skeletal growth, particularly in children.
Rashid’s project is the third from MSU to be funded by the Keck Foundation over the past decade. The philanthropic organization supports research in science, medicine and engineering, with an emphasis on projects that take novel or unconventional approaches with the potential for high-impact results.
“The W.M. Keck Foundation invests in high-risk but high-reward research. Their awards are very competitive and difficult to secure,” said Alison Harmon, MSU’s vice president for research and economic development. “We are very proud that Dr. Rashid’s work has captured their attention and support. It has the potential to make a significant contribution to what we know about inflammation.”
MSU’s two most recent Keck awards have focused on Yellowstone National Park: In 2020, Eric Boyd, also from the Department of Microbiology and Cell Biology, received funding to study the link between seismic activity and the park’s microbial communities, and in 2016, a team led by Brent Peyton in the Norm Asbjornson College of Engineering received a Keck grant to study the organisms that thrive in the area’s hot springs.
The award will fund three years of continued research, which will include explorations of non-pathological inflammation in mammals. The funding will support a research scientist and both undergraduate and graduate student scientists.
“In order to make this applicable to humans and human medicine, we needed to move to mammals and show that this is a universal mechanism,” Rashid said. “So, this grant is to start looking at mammals to build off what we started in birds.”
The fusion of separate bones into a single bone is common in skeletal development, Rashid said, especially in the sacrum and in areas around growth plates such as the arms and legs in humans. Bone fusion in those areas, which are called epiphyseal plates, is a sign of skeletal maturity.
If that fusion is induced through inflammation, then treatment with anti-inflammatory drugs, as is common with conditions such as asthma, could potentially inhibit proper skeletal growth.
“We're still learning which fusions are susceptible to anti-inflammatory drugs,” Rashid said. “This is really important to know, especially for kids who are on long-term corticosteroids and other anti-inflammatory drugs. We need to know what's happening with their skeletons.”
The team will also explore a concept called necroptosis, which is a form of cell death in living bodies. Necroptosis is known to drive inflammation, especially in cancer, and Rashid and her group have evidence of necroptosis playing a role in vertebral fusion. Rashid said that identifying a connection between necroptosis and diseases like ankylosing spondylitis, which results in detrimental fusion of vertebrae in the spine, could lead to new avenues of medical treatments.
For Rashid, who has been exploring these evolutionary mechanisms for more than a decade, the Keck funding shows critical support for a project that is uniquely interdisciplinary.
“We can learn a lot about these bone fusion events throughout the whole skeleton in normal development and disease,” she said. “Because it came from such an unorthodox origin, starting from paleontology and dinosaur evolution and finding this phenomenon, this project has allowed us to look at things from a different perspective and make some discoveries that have been interesting and unique.”
About the W. M. Keck Foundation
The W. M. Keck Foundation was established in 1954 in Los Angeles by William Myron Keck, founder of The Superior Oil Company. One of the nation’s largest philanthropic organizations, the W. M. Keck Foundation supports outstanding science, engineering and medical research. The Foundation also supports undergraduate education and maintains a program within Southern California to support arts and culture, education, health and community service projects.