U.Va.'s Robert Grainger Leads New Developmental and Regenerative Biology Center

Listen to the UVA Today Radio Show report on this story by Fariss Samarrai:

October 22, 2010 — For more than 20 years, Robert Grainger, a biology professor in the University of Virginia's College and Graduate School of Arts & Sciences, has been using a genus of frog, Xenopus, as a model for understanding how the eye develops.

The frog's eye is a valuable study subject because it shares numerous genetic traits with the human eye. There is one major difference, though: The frog can regenerate a lens.

"I'm interested in understanding how cells become committed to making a specific organ, such as the eye," Grainger said. "If we can understand that process, the mechanism by which genes cause an eye or other organ to form, perhaps eventually we can manipulate these genes so that they can be used in medical therapies for diseases that result from defects in these organ-forming genes, and possibly aid in the regeneration of human tissues and organs."

Unlike mammals, many amphibians – and Xenopus in particular – can also regenerate some tissues and organs. Because similar processes appear to occur in the developing embryo and during repair of tissues and organs, the knowledge that is gained through Grainger's and others' work on embryonic development is connected to understanding regeneration.

During the course of his many years of research, Grainger has developed or acquired about 150 genetic lines of Xenopus in two species, X. laevis and X. tropicalis, and now has about 6,000 frogs for study.

His Charlottesville facility, one of the largest in the United States, has served for years as a resource for other researchers at U.Va. and nationally who use frogs to study a range of questions involving organ formation and regeneration, genetics, and the mechanisms underlying diseases such as cancer and diabetes. Grainger's frog project has become so big, and so important to supplying animals for research colleagues in the United States and elsewhere, that more space is needed, as is a fully funded facility for supplying and studying these animals.

Last year, Grainger and a team of colleagues proposed establishing such a center, and Grainger now is the principal investigator for a five-year, $3.4 million grant establishing a national center for housing, supplying and studying the frog at the Marine Biological Laboratory at Woods Hole, Mass. He will serve as the center's executive director, overseeing planning and direction during the first five years.

The grant is provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Research Resources, both parts of the National Institutes of Health. The facility is part of the Eugene Bell Center for Regenerative Biology and Tissue Engineering, made possible by several other large grants.

"Xenopus has become an increasingly important model for a variety of studies that extend beyond individual labs," Grainger said. "It is time that we have this national center."

Such resource centers currently exist around the United States for other animal models used in genetics research, including mice, fruit flies and zebra fish.

Grainger and his colleagues suggested Woods Hole as the best site to establish the facility because the Marine Biology Laboratory is well-equipped for raising and managing aquatic animals from years of experience in growing and maintaining marine animals, and because it is a gathering place for research scientists.

The new center will begin operations in January and will house up to 15,000 frogs within five years, Grainger said. In addition to raising, managing and supplying animals, the center also will host conferences, workshops and seminars to help researchers stay on top of the latest technologies.

Grainger will continue to conduct research and teach at U.Va., but will make several trips per year to Woods Hole. The grant will allow the hiring of some staff at U.Va. for research and management, and his facility at U.Va. will serve as a major backup resource for the two Xenopus species; he will continue to maintain several thousand animals here, primarily for his and his colleagues' own studies, allowing them to focus on producing animal lines specific to their research.

Frogs are a particularly easy animal to study because they are relatively large, they can regenerate many tissues, and their embryos develop externally rather than within a uterus, making them great subjects for understanding embryonic development. Xenopus also are hardy animals that readily reproduce year-round.

X. tropicalis, a species smaller in size than laevis, is a fast-growing frog that has a relatively small genome, making it ideal for development, genetics and mutations studies such as those conducted by Grainger and his colleagues.

"The ability to make mutations to study genes is an incredibly powerful tool," Grainger said. "Because of Xenopus tropicalis' short generation time and simple genome, it greatly enhances our ability to do genetics research."

The research thus far conducted in Grainger's and other U.Va. labs using Xenopus tropicalis played a major role in setting up that particular species as a key research tool in genetics.

"It helps us make exciting progress on questions like how different organs form," Grainger said. "The entire genome of Xenopus tropicalis has been sequenced, as has the human genome, and the similarities in gene organization are remarkable. There is a striking relationship between species, though of course there are some differences as well. We believe that by coming to understand the mechanisms for many biological questions, including early development of organs and tissue regeneration, in Xenopus, we can gain valuable insights that we might apply to humans."

— By Fariss Samarrai