The answers may lie deep inside the common fruit fly buzzing around your kitchen compost.
A Dalhousie University geneticist believes the fruit fly could help provide the information they need to one day help people suffering from HPS and a wide range of devastating, genetic-based disorders.
Working out of the Integrated Transgenic Facility at Halifax's Dalhousie University, Dr. Vett Lloyd is conducting transgenics research that involves taking DNA from one organism-in this case a fruit fly-and putting it in another. "Our facility is unique," says Lloyd, an Associate Professor in Dalhousie's Department of Biology. "It's the only one in the world that's equipped to perform transgenics with the eggs of almost any species."
So why focus on fruit flies? Lloyd says these flies are ideal for studying human diseases. "We share about two-thirds of our disease genes with fruit flies," she says. "Almost everything that happens to a human will happen to a fruit fly." Lloyd says our genetic and physiological similarity with fruit flies means that if a drug or gene therapy approach works with this insect, it's a first indication that it might also work with humans. In many ways, the flies in Lloyd's lab are more than just a little bit human. These "humanized"; fruit flies contain microscopic bits of human DNA that have been inserted into them. And that's what makes them perfect guinea pigs for researchers who, like Lloyd, are conducting experiments with Drosophila to learn how to use gene therapy to cure some of the world's most complex genetic diseases.
Most transgenics labs are equipped to only work with eggs from a single species-for example, fruit flies. But the Dalhousie Transgenics Facility can insert DNA into the eggs of a wide range of species-from the relatively large eggs of zebra fish to the microscopic eggs of brine shrimp. This flexibility is important since some animals are better suited than others for exploring different research questions, from environmental to evolutionary.
Lloyd's research has already made impressive strides. She's shown that it's possible to reverse the debilitating effects of a mutant fruit fly gene by injecting the fly with a working human copy of the gene She's now focused on unravelling the molecular basis for a group of about 40 genetic disorders.
More than once, Dr. Vett Lloyd has received the emotional telephone call from distraught and desperate parents.
"I've had parents calling me up and saying my baby's just been diagnosed with Hermansky-Pudlack Syndrome, how is your research going to help? It's absolutely heart wrenching to say that maybe in 10 years we'll know what's going wrong," she says.
Lloyd, who's an Associate Professor at Dalhousie University's Department of Biology, is stepping up to the medical challenge in an effort to bring hope to all those who have been affected by Hermansky-Pudlack Syndrome (HPS) and a variety of other genetic disorders. In her work at Dalhousie University's Integrated Transgenics Lab, she's using mutant fruit flies as HPS surrogates to explore exactly what goes wrong in both flies and humans with this rare genetic disorder.
In humans, HPS is known to involve at least seven genes. One of the key genes is nearly exactly the same in structure and function as the fruit fly gene-Delta AP3, or garnet. Lloyd has shown that it's possible to cure the fruit fly variant of HPS using gene therapy. "When we insert the working human copy of the gene into sick fruit flies it heals them," she says. "But I don't think this would be the approach of choice with humans." However, by demonstrating that the human and fly versions of the gene are interchangeable, Lloyd has proved that fruit flies are excellent for screening potential drug therapies for HPS.
In fact, Lloyd's lab has screened more than 500 drug compounds with some promising results. Several of the compounds limit the disease by regulating calcium metabolism, known to play a role in protein transport. Lloyd hopes that if she can attract the interest of a pharmaceutical company as a partner, the next step in the research is to test the most promising compounds on zebra fish and mice with HPS-which could lead her closer to the ultimate cure.
The Dalhousie Transgenics Facility is becoming a regional centre for transgenics research. It's actively used by several Dalhousie University biologists, including Ian Meinertzhagen who's studying transgenic sea squirts to better understand the evolutionary origins of the brain. Researchers from Acadia University, and soon Mount Allison University, are also using the facility to carry out genetics-related research.
Along with CFI support, the Transgenics Facility receives funding from the Natural Sciences and Engineering Research Council of Canada and the Nova Scotia Health Research Foundation.
To find out more about current research and human clinical trials with gene therapy, visit the US National Institutes of Health.