For instance, molecular analysis of one of their mutants enabled Ganetzky's group to identify and clone a gene that encodes sodium-channel proteins in brain cells. The influx of sodium ions into brain cells through sodium channels is the essential step in generating nerve impulses.
The isolation of the fly sodium-channel gene has spurred research on insecticide development because sodium channels are key targets of commonly used insecticides, and resistance to these insecticides is often associated with mutations of this gene. Using the Drosophila gene as a probe, other labs have now cloned the corresponding genes in many other insects, including such major pests as cockroaches and mosquitoes.
Moreover, the type of ion channel deficiencies found in some of Ganetzky's fly mutants manifest themselves in humans suffering from such afflictions as epilepsy and cardiac arrhythmias.
"Each fly (mutant) is a door or a window into some biological activity I want to understand," Ganetzky notes. "When those activities are perturbed because of a mutation, the mutant flies become paralyzed at elevated temperatures. Disruption of the same or similar functions in humans could also produce some type of disease manifestation. As a result, these mutants potentially give us some insight into these disorders."
As one example, Ganetzky's group discovered and cloned a human gene known as Herg. That gene was the counterpart to one of the fly genes identified among their many mutants. In humans, mutations of Herg cause a cardiac arrhythmia that can result in ventricular fibrillation and sudden death. Dozens of labs worldwide are now investigating Herg and the potassium channel protein it encodes.