Of Fireflies and Viruses

On a winter morning, Susan Cook takes the freight elevator from her fifth floor lab in the School of Public Health to a storage room on the second floor. Inside that room, she places three anesthetized mice under a camera lens fitted inside a black cabinet the size of a milk crate, closes the door securely, and hits a few strokes on a nearby computer keyboard.

"Now we wait and see," says Cook, a fourth-year doctoral student who studies the effects of single-point genetic mutations on the virulence of the Sindbis virus. One minute later, a photographic image of the three mice appears on the computer screen. But it's no ordinary photograph because superimposed onto the mice's bodies are patches of color: blue and green throughout the mice's midsections, and red over their tiny right feet. "The feet are lighting up," says Cook, as she saves the image to the computer's hard drive, "because the virus hasn't had much time to move."

Three days ago, Cook injected the right foot of each mouse with a strain of Sindbis she'd engineered to express the gene that produces luciferase. Then, just before placing the mice under the camera lens today, she injected each with the substrate luciferin, which reacts with the luciferase in the virus and produces light - just as it does in fireflies. In the mice's bodies, the luciferase in the virus cells becomes a kind of homing device, lighting up wherever the virus is replicating.

Though Cook can't see the light from the virus cells like she can see a firefly's glow, the camera inside the black cabinet can. In fact, the camera which is a highly sophisticated imaging system created by a biotech company called Xenogen literally counts the number of photons emitted from the virus cells in the mice's bodies, and displays those numbers as colors. When Cook sees the mice's feet are covered in red, the color designating a high number of emitted photons, she knows the virus is active there. "I can quantify this data in a minute," says Cook. "Before, it would take me two days."

Until a year ago, when Cook began using luciferase in conjunction with the camera, a method known as in vivo biophotonic imaging, her research required her to inject large numbers of mice, kill them daily, and grind up their organs to assay the location and virulence of the Sindbis cells. "Before this technology, it was impossible to link early data and an outcome in a single animal. Now we're getting more and better data, and having to sacrifice fewer animals," she says. "Also, before you had to know where in the body to look for the virus. Now we can see it even if it shows up someplace unexpected."

Indeed, minutes after Cook repositions the mice in the black cabinet and programs the camera for a longer exposure, something unexpected does appear on her computer screen: a red patch over the neck area of one mouse. "He's already replicating in his spinal cord and brain," she says. "It's earlier than I expected."

Over the next four days, the Sindbis virus will run its course in the mice. And each day, Cook will descend to the storage room, inject the mice with luciferin and anesthesia, and place them in the black cabinet to measure the photons emitted from their bodies. After the mice die, Cook will use the daily snapshots to construct a narrative of the virus that killed them. Each time she injects a new set of mice with a slightly different strain of Sindbis, she'll have the ability to compare its effects with the effects of the other strains. "This is a new way of looking at a virus in a whole animal over time," she says. "It's really exciting."

Diane Griffin, professor and chair of the Department of Molecular Microbiology and Immunology, shares Cook's enthusiasm. "This method had been used before to study bacteria and tumor growth, but no one had applied it to the study of viruses," says Griffin, MD, PhD. "Susan has proved it works. And I think it's going to be broadly applicable for people interested in how viruses cause disease, because almost every virus can be engineered to express luciferase." - Laura Wexler

Connecting Students with Careers

Students can now gain instant access to public health job postings worldwide. And, with one click, they can upload their resumes and cover letters into "resume books" that are searchable by prospective employers. This new e-recruiting system, the brainchild of staffers at the School's Student Academic Support Services, also lists internships and scholarships, complete with application deadlines.

Robert Hradsky, MEd, assistant dean for student services, says School alumni will soon be able to participate as well. An "alumni career advisory network" is being formed whereby School graduates will be able to log in, download their profiles, and list any jobs they've heard about in their fields. Alums willing to be mentors can invite students to spend a day "shadowing" them on the job.

Students interested in finding out more can log on to http://jhsph.erecruiting.com/er/security/login.jsp

- Rod Graham

Malaria Institute's Global Debut

Making its debut in the world of malaria research, the Johns Hopkins Malaria Research Institute hosted a unique, multidisciplinary conference in late January on malaria science in the genomic era.

Unlike others, this malaria conference offered a smorgasbord of topics from history to parasitolgy, genomics, and mosquitoes.

"We attracted the best people in the field," says Diane Griffin, chair of Molecular Microbiology and Immunology. "The quality of the talks was superb."

While most malaria conferences focus on one or two fields, "Malaria: Progress, Problems, and Plans in the Genomic Era" covered topics in history, genomics, vaccines, parasitology, molecular biology, drug resistance, and mosquitoes. "We're dedicated to the idea of getting multiple disciplines within the malaria field together," says Griffin, MD, PhD. "We specifically invited people on the cutting edge, approaching things differently or doing the newest kinds of things."

More than 200 attendees and 30 speakers came to Baltimore for the three-day event that began Jan. 27. They came from all over the United States, as well as Sweden, Great Britain, Switzerland, South Africa, and Malawi. Researchers from the different fields enjoyed a rare chance to interact and exchange perspectives about the disease that kills 1.5 to 3 million people every year. "It was an opportunity to forge collaborations and to find out some of the latest work that's being done," says David Sullivan, MD, assistant professor in MMI.

Conference speakers have been invited to contribute articles based on their presentations to a thematic issue of the International Journal for Parasitology. Hopkins MMI Professor Nirbhay Kumar, PhD, will serve as special editor for the articles.

Founded in May 2001, the Johns Hopkins Malaria Research Institute welcomed its first new faculty member in February. Associate Professor Fernando Pineda, PhD, an expert in bioinformatics, has a primary appointment in MMI and a joint appointment in Biostatistics. Griffin expects to hire three or four faculty members this year, of the ten or more to be hired for the Institute.

The Institute has also announced plans to partner with the Virginia Bioinformatics Institute to use its computer expertise to do advanced bioinformatics research on malaria. - Brian W. Simpson


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