Chipping away at parasites

Chipping away at parasites

Maeve Haldane | When Terry Spithill says there's a strong infectious disease community in Montreal, he means it in the best possible way. A new Canada Research Chair, Spithill was brought over from Australia to direct the Institute of Parasitology, and he's pleased as punch to be among so many like-minded researchers.

Institute of Parasitology director Terry Spithill PHOTO: Owen Egan

The Institute, one-of-a-kind in North America, Spithill explains "was set up in 1932 by the Empire Marketing Board, the Quebec Ministry of Agriculture and the National Research Council to address the problem of parasites in production animals here in Canada." Seventy years later it's going strong thanks to $12 million of Canada Foundation for Innovation money to be shared with McGill's Microbiology and Immunology Department, McGill's Centre for Host Resistance and the Armand Frappier Institute.

Researchers are waking up to the fact that so much economic underdevelopment is due to the poor health of people and animals, often caused by parasitic diseases. Spithill points out that "if Africa is going to move forward and grow out of its economic woes, we need to improve the health of the people." And he believes that better-off countries like Canada can have a huge impact on global health problems through research as well as by training the next generation of scientists. The Institute actively hosts and trains graduate students from developing countries around the world.

A biochemist by training, Spithill says he "studies both protozoa (single cell parasites) and the liver fluke, which is a blood-sucking worm." These small worms cause big problems. He has spent years on livestock-debilitating Fasciola gigantica, aka tropical liver fluke, in Indonesia.

Liver fluke infections starts when the parasite hatches in the gut after the animal eats contaminated grass. The fluke migrates to the liver, causes fibrosis and tissue damage, eventually entering the bile ducts where it becomes an adult blood-sucking parasite.The blood loss causes anemia, the liver damage affects the animal's physiology, and the overall effect is an animal that is smaller. "Over two years of infection, a fluke-infected cow loses 15-20% of its body weight," Spithill says.

Spithill explains that this 15%-20% reduction in weight results in weaker animals to till fields, lower fertility in cows, and eventually, less meat on the bones to sell. What should be a 300 kg cow may weigh 230 kg, and at $2 a kilo, that's a loss of $140, a substantial amount for a subsistence farmer in Indonesia who makes about $800 a year. "Worldwide, we think the net effect of this single parasite infection is over $3 billion (U.S.) in lost productivity."

"If we cure this one parasite, we can increase animal productivity by 15%-20% overnight in many areas of the world. And there aren't many technologies that can do that."

More recently, Spithill is starting to use proteomics, "which is understanding the function of the proteins coming from the genome," to work on a multivalent DNA vaccine for malaria.

Spithill explains that with DNA vaccines a gene that codes for a malaria protein is put in a plasmid (circular DNA taken from bacteria that can't replicate in mammals). "The plasmid is injected into the skin, the gene gets expressed inside the host cells and the protein is released, which subsequently induces an immune response to the parasite."

Spithill's team took small bits of malaria chromosomes, 30,000 genes at a time, put those in a plasmid that was injected into mice. "The idea was if there were candidate vaccine sequences in that pool of 30,000 plasmids, you'll get protection from malaria. This is what we observed, and we are now subdividing these plasmids to identify maybe 10-20 genes that are new vaccine candidates."

Spithill's excited about getting a CFI-funded protein chip mass spectrometer to help discover the function of merozoite surface proteins, or MSPs -- key targets for a vaccine. Merozoites are the invasive stage of the malaria parasite. "A malaria fever is the merozoite bursting out of your red blood cells and invading new red blood cells -- it happens every 48 hours." Spithill says, "the problem is we don't know what proteins are on the surface of the merozoite." That's where the mass spectrometer will come in handy.

Spithill will use bioinformatics to select malaria proteins of unknown function, bind these to a chip surface, then incubate a known malaria extract with that protein. If the proteins in the extract bind, "this machine has a laser that zaps this protein that has bound to the chip off the chip, and puts it into a mass spectrometer.

"The spectrometer identifies the mass of the protein and sequences it." Then it's compared to sequences in the computer database, looking for a match in the malaria genome sequence. "If you can get an unknown protein to associate to a known protein then you have a clue as to what the unknown protein does or might be doing!" Once we identify new MSPs these can be engineered into new vaccines.

The Institute's members have a broad range of interests from a variety of parasites to immunology to drug development. Although some would see this as a weakness, Spithill sees the diversity as a strength. "If you're working on different parasite systems you can get cross-fertilization of ideas. What's discovered in one system may have applicability in another system that you wouldn't even hear of if the person wasn't having coffee with you over lunch and talking about their result."

At the moment, the Institute's biggest worry is being a victim of its own success. "We've been so successful in getting grants, recruiting new staff, attracting students and getting CFI funds, we're actually running out of laboratory and meeting space." Spithill hopes for a new biotechnology laboratory to be built at Macdonald campus for use by all the biotechnologists on the campus to create a critical mass in this technology. He plans to set up a bioinformatics lab at the Institute to assist proteomic research. Spithill's keen to raise the Institute's profile, create an alumni database and promote fundraising.

"I hope to recruit new people here, but I've got nowhere to put them. So success is creating a problem," Spithill says. "But it's a good problem to have -- it's an exciting time to be here."