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Thursday October 26 4:30 PM ET
U.S. Scientists Watch Gene Changes As Worms Grow
By Maggie Fox, Health and Science Correspondent
WASHINGTON (Reuters) - Scientists using a ``gene chip'' and a beakerful of ground-up roundworms said on Thursday they had been able to watch genes turn on and off as the worms were born, grew and died.
The experiment is the first in which researchers have been able to watch, almost live, the genetic activity in an entire animal, and document how it changes as the animal lives and grows.
``It's the first time that people have been able to observe all the genes in a multicellular animal at once,'' Andrew Hill of the Genetics Institute in Cambridge, Massachusetts, who led the study, said in a telephone interview.
They hope the technology might be applied soon to the study of human genes. It would be one way to decode the giant mass of information supplied by the public and private efforts to map the human genome -- the entire collection of human genes.
One immediate observation was how genes change activity as the nematode worms age.
``When we monitored the expression of genes in worms two weeks old -- these worms are close to dying -- we find that genes that may be important for normal muscle function and normal energy expression are turned down,'' Hill said.
``We hope that helps provide a clearer picture of how the aging process affects gene expression.''
Hill's team, working with worm experts at Harvard University, used what is called an oligonucleotide array to watch the gene activity. It is very similar to the ``GeneChip'' patented by California-based Affymetrix Inc. (NasdaqNM:AFFX - news)
``An oligonucleotide is a short stretch of single-stranded DNA,'' Hill said. Each strand has about 25 of the nucleotides -- the A's, C's, T's, and G's -- that make up DNA.
``On this array you have hundreds of thousands of different oligonucleotides. Each small oligonucleotide is complementary, or binds to a specific message from a certain gene.''
To make sure they got genes that were actually working, as opposed to staying dormant, they used RNA, the working version of DNA, from the worms.
``We put that RNA on the chip and what happens is that each RNA from each gene goes and binds to its partner on the chip, if it is there. Once it is bound, can stain it with a fluorescent dye which only lights up bound areas. Then you can scan it with a laser and see which spots light up.''
Nematode C Elegans Gives Up Gene Secrets
They used RNA from batches of worms of different ages. The worm of choice was Caenorhabditis elegans, a roundworm whose entire genome was sequenced amid great fanfare a few years ago.
``We looked at worms at about 8 different stages of development,'' Hill, whose findings are reported in Friday's issue of the journal Science, said. ``That enabled us to get a picture of how the worm looks like when it is an egg, when it is a young larval worm, and as an adult.''
Of the 19,000 known genes in C. elegans, Hill's team detected 10,000.
``The ones didn't see are probably ones that are expressed at low levels in specific tissues,'' Hill said.
Next, the group wants to look at individual tissues and organs from their worms. ``One of the issues with our experiment is that we collected entire worms because we wanted to see what expression was like from all tissues,'' Hill said.
``The disadvantage was that genes that are only expressed in say one tissue, like the brain, would tend to be diluted.''
They have already found some genes that light up when the worms' gonads are separated and tested.
Because worms and humans have a large number of genes in common, the findings could eventually be used to help understand human biology.
``Certainly, eventually people will make arrays that would cover the whole genome directly,'' Hill, whose institute is owned by drugmaker Wyeth-Ayerst (NYSE:AHP - news), said.
