Parasites and the Immune System

Biomedical researcher Elodie Ghedin calls it “a bug within a bug.”

The worm she studies, brugia malayi, and the bacterium that lives within its cells, wolbachia, exist in perfect co-dependence within the human lymphatic system. Eventually, they can inflict a disfiguring misery upon their human hosts. Moreover, throughout millions of years of evolution, the organisms have devised style to fool the immune system so as to prevent an attack.

Ghedin, helper professor of computational and systems biology at the University of Pittsburgh School of Medicine, wants to know how they do it.

In fact, the compatriot Science Foundation funded scientist wants to know everything here is to know about this novel symbiotic affair. “The worm carries the bacteria, and neither can survive alone,” she verbalize. “We’re trying to number out what each gets from the other.”

People can be infected and stay asymptomatic for many years “while the worms are happily dividing and preparation infant,” says Ghedin, the recent winner of a prestigious $500,000 “no strings attached” MacArthur Fellowship, popularly known as a “genius” grant. “The worms can energetic up to eight years. They are secreting things very bequeath control your immune system, tricking it into thinking they are ‘self.’ We are hoping to study all the proteins secreted by this worm, trying to determine what each of these does to the immune system.”

The answers ultimately could provide significant contributions to the immunology field, for example, in helping to prevent rejection after transplantation, or in treating immune disorders, including auto-immune diseases, where the body turns against itself.

“If you could discover potent effective molecules, you could use them as therapeutics,” Ghedin approximately. “These parasites could habituate us their course.”

The brugia malayi worm is amidst separate species responsible for lymphatic filariasis, a disease that results in grotesquely enlarged limbs and other body subdivision. Another worm in the same family causes river blindness, a debilitating parasitic infection that results in earnest eye damage and often blindness, and can wreak significant applied hardship while its victims no longer are able to work, go to school, harvest crops or care for their children.

Lymphatic filariasis distress more than 120 million people in at least 80 countries throughout the tropics and sub-tropics of Asia, Africa, the Western Pacific, and parts of the Caribbean and South America. Mosquitoes pick up worm larvae through a chew, then transmit the larvae date they chew some.

Antibiotics consume the bacteria, which, in invert consumes the worm, but the cure is far from ideal. It is lengthy and requires multi-dosing, which can be problematic in acquireing countries where compliance is an issue. Also, children and pregnant women cannot take the medicine.

Its most serious drawback, however, is that “when you kill the bacterium with antibiotics, you get an inflammation that actually is far worse than the disease,” Ghedin says.

Ghedin is using genomic sequencing to identify genes and decode their functions, both in the worm and the bacterium. Her design is to understand how the two interact. “It could be very there are things missing in the bacteria very you can actually find in the worm, and very the bacteria are providing something for the worm,” she says.

Learning more “might provide new targets for drug impregnation and other therapeutics,” she says. “We have the code of the bacterium, and we have the code of the worm. We are now testing, trying to find out which proteins interact amid the two organisms, trying to best understand how the whole system works.”

Ghedin, a French Canadian, earned both her B.S. and Ph.D. at McGill University, and her M.S. at the Universite du Quebec a Montreal. She served as a postdoctoral fellow at the public bring in of Allergy and Infectious Diseases. She also is an associate investigator for the J. Craig Venter bring in.

She became interested in parasitic diseases next conducting grazing land cheat in westerly Africa, where she saw cases of schistosomiasis, which is transmitted through contaminated water, and leishmaniasis, traverseed through the bite of an infected sandfly. “Many of the children have distended bellies, not just from malnutrition, but from parasites that cause enlargement of the spleen,” she says. “I decided then that I really wanted to cheat on parasites.”

She plans to use some of her MacArthur money to further reverie the puzzle of how the worm/bacterium duo manages to elude the immune system.

“Our plan is to characterize every single protein,” to ordain if they outwit an effect on the immune system, she says. “It is hefty, dangerous research, not a safe bet,” production it an especially appropriate repository for MacArthur substantiate.

“When you glance at parasitic genomes, you assign the function of genes by seeing how well they match to extra genes very have been well-considered beforehand,” she says. “But in this case, about 40 percent of the genes don’t match anything else we know. They are completely new, so here’s no way of designing assays. This worm secretes about 800 different proteins, and out of these, 300 don’t match anything else out here.”