ONE example of how unravelling the genetic blueprint of the nematode worm can aid humans was reported recently in research that points the way to a new type of treatment for diabetes.
Diabetes is caused by lack of insulin and affects about five per cent of the population; genes found in the worms provide new targets for drugs to treat diabetes, and "humanised" worms could even help test these drugs.
Helped by the latest information from the effort to sequence the genetic code of Caenorhabditis elegans, Prof Gary Ruvkun's lab recently found that a gene that regulates the metabolism of the worm is equivalent to the human insulin receptor gene, which governs how the body reacts to insulin.
Now a new analysis, reported in the journal Nature by his team from Massachusetts General Hospital in Boston, has revealed that turning off a gene - daf-16 - enabled the worms to cope without their version of the insulin hormone.
Because the metabolic defects in worms with faulty insulin signalling are "cured" by turning off the daf-16 gene, the work implies that insulin may control sugar metabolism via inactivation of daf-16.
"Our discovery that animals do not need insulin signals if they also carry an inactive daf-16 gene was completely unexpected," said Prof Ruvkun, "and points the way for the development of an entirely new class of anti-diabetes drugs."
The protein produced by the daf-16 gene appears to shuttle signals from insulin receptors in cell membranes to the nucleus, where it regulates other genes.
The team reports that humans carry two daf-16 equivalent genes that may similarly pass along insulin signals. These genes may be defective in some diabetics , according to Prof Ruvkun. As a result, changes in gene expression may occur that in turn lead to the metabolic defects of diabetes.
"We envision developing drugs by screening for them in worms that carry the human equivalent of daf-16," he said. For example, such "humanised" worms can be screened for drugs that inactivate the human daf-16 protein.
The Nature paper also shows that another metabolism-regulating hormone conspires with insulin to regulate C. elegans metabolism, and suggests that the human equivalents of the other genes in this parallel signalling pathway may also be defective in diabetics.
The researchers are now beginning to search diabetic patients for mutations in the human genes that are the closest relatives of these worm genes.
Even if their theory is correct and drugs can be developed, Prof Ruvkun cautions they may have side effects that disqualify them from use. "Still, we believe that our research suggests novel avenues for the treatment of diabetes."
