Hooked on Genomics

Jane Carlton is an addict. She hides it well behind her soft British accent, gentle smile and meticulous office. But in a remote corner of New York University’s Department of Medical Parasitology, she spends vast amounts of taxpayer dollars to feed her unlikely habit: parasite genomics. That’s right, Carlton gets her fix by sequencing the DNA of parasites. But unlike other addictions, this multimillion-dollar habit might just help solve some of the world’s leading health problems, from fatal malaria to itchy genital bugs.

In early January Carlton’s most recent genome results flooded the international media. She spent most of the following two weeks speaking with media outlets, science podcasters and university publicists about her research, which made the cover of Science . The paper detailed the genome for the vaginal parasite Trichomonas vaginalis.

“The malaria genome didn’t get nearly this much press,” Carlton remarks, mentioning that the tragic sniper shootings in Washington, D.C., stole the headlines soon after the malaria genome had been published. Then again, “sex sells,” she admits. Considering that “Tee-vaj” (as Carlton affectionately calls it) is the most common sexually transmitted infection in the world, Science no doubt had more than titillating pictures in mind when they put this project on their cover.

T. vaginalis resides primarily within the urinary and genital tracts of both men and women. Despite having two drugs on the market to treat the infection, the parasite persists because only half of the women infected ever experience its classy symptoms – vaginal itching and a foul-smelling frothy discharge (“It’s a farty little bug!” says Carlton). Men normally don’t come down with symptoms. This means that half of infected women and nearly all of the infected men act both as carriers and a reservoir for the parasite, making it difficult to eliminate. The World Health Organization’s official statistic of 170 million cases per year may actually be an underestimate, because people only get tested for it when they display symptoms.

There isn’t a lot of money out there for the small research community that studies this group of parasites, most likely because the bugs don’t actually kill people. It’s a small miracle that such a limited community could muscle their way into government-allotted science funds. “It was the NIH who had the foresight” to set aside funds for a genome project, says Carlton “They identified nine key organisms that had significant public health issues, and T. vaginalis was one of them.” And so the publishing of the T. vaginalis genome has made freely available the complete genetic repertoire of the parasite, allowing for more detailed investigations into the biology of the bug, the infection that it causes and new drugs that could be used to treat the infection.

Carlton’s gateway into genomics was the world’s most infamous parasite, malaria. During her doctoral research at the University of Edinburgh, she struggled with genetic crosses of malaria parasites in an attempt to map where, exactly, the secret genes of drug resistance resided. She realized that she needed good genetic markers, which act like little postal codes for genes and are best defined through full-scale genome projects. And so after completing her thesis, she moved to the University of Florida to pursue malaria genomics directly. “When I heard that a lab in Florida was looking for a postdoctoral fellow, I jumped at the chance to get involved,” she says of her timely good fortune.

Carlton’s work in Florida introduced her to the folks at The Institute for Genomic Research (TIGR) in Rockville, Maryland. After attending several of their meetings, she began to work peripherally on the genome of the most virulent malaria parasite, Plasmodium falciparum – the species responsible for 90% of all malaria deaths, primarily in children of sub-Saharan Africa. In 2001, TIGR approached Carlton to head the project on another malaria genome project, and she couldn’t say no. It was this move to TIGR that launched her interest in comparative genomics. “Once you sequence one parasite genome,” she says, “one genome is not enough.”

Her addiction grew more powerful over her years on faculty at TIGR. “I just started sequencing anything that moves,” says Carlton, whose past and present projects include Theileria parva, (responsible for East Coast fever in African cattle), Toxoplasma gondii (a parasite that lives in cats and causes birth defects in people), species of Cryptosporidium (a group of bugs that cause acute diarrhea) and more work on Plasmodium. All these parasites come from the same phylum of protozoans, Apicomplexa, giving Carlton a unique set of DNA to compare and contrast. “You need to sequence different species,” argues Carlton. “Then you can begin to compare genomes, figure out what’s different and why one is more virulent than another.”

Carlton is not just a user, she’s also a pusher. Working on malaria has meant working with scientists from developing countries. Early in her career Carlton felt compelled to train scientists from areas hardest hit by the diseases she studies. “The great thing about genomic data is that you can analyze it in silico,” she says, alluding to how much genomics work can be done on computers. “It’s freely available to everyone, so there should be a way of getting that data out to developing-country scientists so that it’s not just the developed countries that have the power.” Her most recent effort to bridge this gap was to create a training partnership between New York University and the National Institute of Malaria Research in Delhi. She plans to bring Indian scientists to the United States for exposure to research techniques and facilities here, meanwhile sending North American faculty to India to teach. “We can’t just take-take-take from developing countries,” Carlton says. “We’ve got to give something back.”

Her next fix? Plasmodium vivax. Though not as lethal as P. falciparum, this malaria species infects more people worldwide and has a far greater range, persisting in Africa, Asia and South America. She plans to launch the P. vivax genome study as a comparison between four different malaria species. She’s hoping to find clues into drug targets common to all species and to gain insights into differences in virulence or lethality. Please note that only an experienced user of Carlton’s caliber should attempt such an intense study. And let Carlton be an example for all those considering genomics: be careful, or you might get hooked.