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WEB EXCLUSIVE: URI Professors breaking new ground on Lyme disease

February 12, 2011

KINGSTON--When South African writer Nadine Gordimer was asked what was the best compliment she had ever been paid she said, "Years and years ago, when I was on a camping trip on a farm, I was bitten by ticks that had brushed off the long grass I'd been walking through. When I complained of this, the old and very unattractive farmer said, 'If I was a tick, I'd also like to bite you.'"
The 20,000 people who contract Lyme disease each year do not feel complimented. The thirsty ticks, part of the arachnid family, are indiscriminate feeders and are still active in weather above 45 degrees. In southern New England, deer ticks have been seen feeding even in the chill of December and January.
But perhaps a new possible scientific pathway will allow for carefree nature hikes in the future. A recent academic collaboration between URI Professors Roberta King and Thomas Mather is working to prevent Lyme disease by studying the inner workings of ticks.
King and Mather were an unlikely collaboration--the two scientists study completely different subjects. King is a biochemist who researches enzymes and proteins, specifically, sulfotransferases (sul-FO-trans-fir-ezeSUL-fo-TRANS-fir-aze-es) which contribute to balancing and regulating numerous biologically active compounds such as estrogen and dopamine. Meanwhile Mather, an entomologist, is (in King's words) a "tick guru" who has been researching vaccines against Lyme disease for more than a decade.
"I never knew anything about ticks or non-human, non-mammalian disease," King admitted in a phone interview.
"But this is a very exciting collaboration. I can apply my expertise from studying human metabolic changes in relation to cancer to prevent illness. Through this collaboration, I am looking at to similar metabolic changes in ticks to which may also prevent human illness."
Working to disentangle the web of mysteries within the tick genome, Mather’s group noticed a connection--a code--for sulfotransferase in New England ticks: Gene levels corresponding to the DNA code for two sulfotransferases differed before and after ticks had fed. What caused this change in levels? Why are the bloody little bugs using their precious energy to do this? This question led Mather across the Kingston campus to King in the College of Pharmacy.
Mather contacted King in 2006, knowing she was an expert on the changing sulfotransferase proteins. He described his work and asked if King was interested in collaborating. Knowing the functions of sulfotransferases in humans she was intrigued, She agreed and both began by allowing one of their respective researchers to begin investigations. King’s lab focused on the biochemistry and learning the function of the enzymes. Mather’s lab focused on the molecular biology and in proving that the changes occurred in live ticks.
“My lab made computer models of each tick sulfotransferase to predict their biochemical function. Then we used samples from the live ticks to prove that dopamine, a common neurotransmitter, could be turned off by the enzymes,” King explained.
When King herself began testing, she argued that dopamine (a neurotransmitter) was making the test ticks salivate, allowing them to feed. Ticks in the lab were given dopamine as a test. Sure enough, the ticks salivated. According to King, dopamine is the signal that controls release of tick saliva.
"Eureka!," King said. "If we could interfere with the sulfotransferase... which would interfere with the dopamine signal...then that might interfere with salivation...which would hopefully prevent ticks from feeding on their host!" Since it is during feeding that ticks transfer the dreaded bacteria which causes Lyme Disease, this is big news.
"We don't have to stop the initial bite as much as we need to shorten the feeding process," King said. "With these long-feeding ticks (they typically feed for three or more days), if we shorten the attachment time by interrupting salivation, then we may have an effective way to stop transmission of Lyme disease."
The portion of the research conducted in King’s lab will be published in March in the journal ACS Chemical Biology. The portion conducted in Mather’s lab has been submitted and will be published later this year.
"There are a number of ways to interfere with the sulfotransferase. We can slow the enzyme or stop it by putting in a chemical that could inhibit it from working," she said. The ticks would need to be exposed to the chemical or humans would need to either apply the chemical or have it introduced into their bloodstream.
But such elixirs are at the top of a canopy of future research. Applying for and receiving grants as well as getting published will certainly be part of the climb. Whether time and effort in the near future will reveal solutions is still unknown, but however long the research takes, the scientists should remember as they begin: Be careful of the long grass.

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