Seattle Researchers Help Crack The Genetic Code Of Three Deadly Parasites

By Mausmi Mehta

An international alliance that includes the Seattle Biomedical Research Institute (SBRI) has completed sequencing the genetic material of three parasites--a project that has taken nine years and cost $60 million. These three parasites cause Chagas disease, African sleeping sickness and leishmaniasis, and infect millions of people in poor, developing parts of the world.

No vaccines protect against the diseases, and the drugs available are inadequate and highly toxic–some are from the 1900s and based on antimony and arsenic. The parasites' genome sequences have given scientists and drug developers a genetic blueprint of each parasite, describing every target that may be vulnerable to attack, and have opened the door for new therapies.

SBRI researchers Peter Myler and Kenneth Stuart co-authored three papers in an issue of the journal Science last July that was dedicated to the genome sequences of the three parasites.

Over two hundred scientists from 47 laboratories in 25 countries participated in the momentous sequencing effort. The team included SBRI, The Institute for Genomic Research in Maryland, the Wellcome Trust Sanger Institute in the UK, and the Karolinska Institute in Sweden.

Funding for the project was provided by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health; the Wellcome Trust; the Burroughs Wellcome Fund; the Beijer Foundation; the WHO Special Programme for Research and Training in Tropical Diseases; and the European Union.

The data were made available to other researchers during sequencing, and two studies published along with the genome sequences have already used it to answer basic questions about the parasites' physiology.

All three parasites are single-celled organisms known as trypanosomes, and are collectively referred to as the TriTryps. Even though the parasites are only distantly related to each other, and are transmitted by different insect vectors, their genome sequences revealed a surprising similarity.

"Initially, we believed that the gene organization among the parasites would be very different, but seventy percent of the genes occur in the same order," says Myler, who is also a faculty member at the University of Washington's School of Medicine and School of Public Health and Community Medicine. "The core genome of all three is very similar, with the differences mainly at the end of chromosomes. So that tells us that if we focus on the genes that are the same in all three, but different from humans, we have the potential to develop a class of drugs that can target all three diseases."

The genome sequences have provided scientists with a 'parts list' for each parasite, but more experimental and computational research is needed to determine exactly what each gene does and whether it will be a suitable target for drug development. And since there are eight to twelve thousand genes in each of the three parasites, this will take a significant investment of time and money.

A number of non-profit and academic groups around the world are working to develop new treatments against the TriTryps, and SBRI researchers are currently exploring ways to collaborate with them in order to speed up the process. However, since the pharmaceutical industry sees no profit to be made in the poor countries where these diseases occur, the researchers must rely on the generosity of foundations and government funds.

The groundwork has been laid for designing new therapeutics that may finally eliminate these parasites. But scientists need "resources and commitment on a far larger scale to transform drug targets into clinical successes," writes George Cross in an editorial accompanying the TriTryps genome paper. "It is clear that the traditional pharmaceutical industry will not become effectively involved in this area, and the current promotion-and-reward system in academia does not attract or sustain the necessary human and financial resources," he notes. "Perhaps we need research institutes that are solely dedicated to drug development for 'diseases of the poor,'" Cross suggests.

Mausmi Mehta is a Ph.D. candidate in biological oceanography at the University of Washington.