The recent completion of the genetic mapping of a common soil-dwelling worm is likely to put a companion research project in Oklahoma on the map for scientists around the world.
The project could make the Oklahoma Medical Research Foundation in Oklahoma City a high-tech worm farm.
On December 11, an international research team lead by Robert H. Waterston of the Genome Sequencing Center at Washington University in St. Louis announced it had mapped the gene pattern of a tiny roundworm, Caenorhabditis elegans.
The team, which included researchers at the Sanger Centre in Cambridge, England, had been working on the worm genome sequence for eight years.
As the sequencing team mapped the worm genes, Dr. Robert Barstead, a geneticist at the Oklahoma Medical Research Foundation, has been trying to identify the function of each gene.
Barstead completed a post-doctoral fellowship under Waterston in St. Louis and has been working in tandem with the genome sequencing team since coming to the medical research foundation two years ago.
Working under a $1.2 million grant from the National Institutes of Health, Barstead’s research group has already “knocked out,” or deleted, 3,000 worm genes or parts of genes to understand what each does.
“Mapping just tells the gene’s location on the genome,” Barstead said. “Knocking out the gene helps us learn about what functions each gene performs or controls.”
Using the genome sequence, Barstead has begun developing genetically altered works that scientists worldwide can use as research models for studying disease.
“A Genome is basically a set of instructions for building the animal,” Barstead said. “But so far, those instructions are in a language that’s unknown to us.”
Barstead used the car as an example.
“If you want to understand a car, one way to do that would be to take parts off – like the carburetor or the brakes – and then test its operations.”
“That’s exactly how we are studying the genetic functions of C. elegans,” Barstead said.
Because the full worm sequence is known, the medical research foundation’s genetically altered worms will make it easier for scientists to speed up their own research studies.
Barstead’s “worm zoo” was pictured in the December 11 issue of Science on a story on the sequencing of C. elegans.
The Oklahoma Medical Research Foundation, the Sanger researchers and the University of British Columbia in Vancouver have formed a consortium to speed the study of the C. elegans gene function and to generate large numbers of mutant worms.
So far, the consortium has identified the function of some 7,000 worm genes.
Foundation President Dr. J. Donald Capra said Barstead’s project is the second step now that the gene mapping is done.
“The complete sequence of an animal genome – as opposed to bacteria – is a landmark event in biology,” Capra said. “We are fortunate to have biomedical science in Oklahoma City that dovetails into that project.”
The foundation is “committed to research in the ‘post-genome’ era,” Capra said. “These approaches to ‘functional genomics’ will start with worms, progress through mice and eventually be applied to human beings.”
Capra said Barstead’s worm research could dramatically affect the study of any disease with a genetic component, such as cancer, diabetes, multiple sclerosis and muscular dystrophy.
C. elegans is not a worm anyone would use as bait.
A dozen of them could perch on the head of a pin.
Thousands of the tiny multi-celled creatures – a common type of nematode – can live in a handful of soil, where they eat bacteria for lunch.
What makes C. elegans so popular with researchers is that it shares 40 percent of its 19,990 genes with humans.
The worm has only 959 cells, yet it reproduces, grows into a mature adult, eats, excretes and dies with many of the same cellular interactions of other animals.
“The worms are a great model for human genetics,” Barstead said.
By understanding what happens in the worm’s cells, researchers also learn what happens in human cells.
Of the 5,000 best-known human genes, 75 percent have matches in the worm.
In fact, some worm genes are so similar to human genes that researchers have experimentally inserted human genes into the worm and watched as the implants worked perfectly.
This is what also makes the worms such desirable models for studying human disease, Barstead said.
Genes for muscles are almost identical, he said.
In addition, in the nervous system, some genes discovered first in the worm were later found also to be in humans, although the worm has only 302 neurons compared with a human’s millions.
Most of the genes chosen in the first phase of the knock-out project are ones that scientists believe are involved in particular disease or are vital to understanding basic human biology.
“The mutant worms… are a means to search through panels of chemicals for those that have an effect on a worm that’s been genetically altered in a way that links it to a particular disease,” Barstead said.
