Of Fireflies and Viruses
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."
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
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
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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