Sunday 22 January 2012

Devastating blood fluke's code cracked

Genelle Weule
ABC


Scientists have unravelled the genetic code of the blood parasite that causes an insidious tropical disease linked to bladder cancer and HIV/AIDS in Africa.
The international team, led by Dr Neil Young from the University of Melbourne, sequenced the genome ofSchistomosma haematobium.
Their work, which is published this week in Nature Genetics, also identifies possible targets for the development of drugs and vaccines for schistosomiasis, also known as bilharzia or swimmer's itch.
Schistosomiasis is spread to humans from small larvae shed from freshwater snails. The larvae burrows into the skin and travels through body to eventually develop as adult worms in blood vessels surrounding either the intestines or the bladder and genital tract, where they breed and cause chronic infection.
Of the three main species of parasite that cause schistosomiasis, Schistomosma haemotobium causes the most devastating form, says Young.
Affecting around 112 million people in Africa,Schistomosma haematobium causes chronic urogenital tract disease and is linked to bladder cancer and susceptibility to HIV/AIDS.
The two other major species — S. mansoni which is found in South America and Africa, and S. japonicum, which is found in China, cause intestinal and liver disease.
"While the intestinal form of the disease, which is caused by S. japonica and S. mansoni is important, S. haematobium causes more than half the infections in Africa," says Young.
There is currently no vaccine and only one drug available to treat S. haematobuim infections.
Young says most of the research into the disease is based around S. mansoni which was mapped three years ago along with S. japonica.
"Having genomic maps for all three species is essential," he says.
"When you're searching for drugs and vaccine targets you have to know that they are going to treat the majority of infections," he says.
But until now, research into this species has been "put in the too hard basket" because the species' host snails don't take well to laboratory life.
Using single cell sequencing, the team extracted the nuclear genome from a single pair of worms by amplifying DNA taken out of a single cell.
"That's a tremendous breakthrough because it means we don't have to grow the animals in the lab," says Young.
Proving the technique works makes genetic sequencing more effective and opens the way for studying other types of neglected parasitic diseases, says Young.

Target proteins

Their analysis of the genome reveals that S. haemotobium has a similar number of genes and genetic structure to the other two species, but is most closely related to S. mansoni.
Young says the research will help scientists identify common proteins that can be knocked out or targeted with new or even existing drugs.
"For the first time we can start to look at the similarities from a drug and vaccine perspective and it will be interesting to see what biological differences there are between these species," he says.
By comparing the genome to the other two species and model species such as roundworms (C. elegans), fruit flies and mice the researchers identified six molecules as possible prime targets for drugs that may be effective against all species of the fluke.
He says the group's research will also allow scientists to hone in on other species of flatworms — a distinct evolutionary group closely related to molluscs — which cause human and animal diseases.
Their analysis identifies thousands of common proteins found in other types of flatworms such as liver flukes that infect cattle.
The genome sequence is publicly available in a database that also contains the blueprints of the other two species.
"We wanted to make it a comparative resource, rather than have one genome in one place and another genome in another," says Young.

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