In a laboratory at Michigan State
University, scientists took a DIY approach to build a retrofitted cryo-electron
microscope that allowed them to map a giant Samba virus -- one of the world's
largest viruses.
"If the common cold virus is
scaled to the size of a ladder, then the giant Samba virus is bigger than the
Washington Monument," said Kristin Parent, assistant professor of
biochemistry and molecular biology and co-author of the paper featured on the
cover of the journal Viruses. "Cryo-EM allowed us to map this virus'
structure and observe the proteins it uses to enter, or attack, cells."
It seems counterintuitive that bigger
organisms are harder to see, but they are when using cryo-electron microscopy.
That's because these microscopes usually are used to look at thin specimens and
can't decipher larger organisms to reveal their biological mechanisms. For
thick samples, scientists see only dark gray or black blobs instead of seeing
the molecular framework.
Cryo-EM allowed Parent's team to image
the giant Samba virus and understand the structures that allow it to enter an
amoeba. Once inside, Samba opens one of its capsid layers and releases its
nucleocapsid -- which carries the genetic cargo that sparks an infection. While
Samba isn't known to cause any diseases in humans, its cousin, the mimivirus,
may be a culprit for causing some respiratory ailments in humans.
"If you scoop up a handful of
water from Lake Michigan, you are literally holding more viruses than there are
people on the planet," said Parent, who published the paper with Jason
Schrad and Eric Young, MSU biochemistry and molecular biology graduate
students. "While scientists can't study every virus on Earth, the insights
we glean from viruses like the giant Samba can help us understand the
mechanisms of other viruses in its family, how they thrive and how we can
attack them."
As bacteria become more resistant to
antibiotics, looking for new ways to fight diseases will continue to grow in
importance. Parent's lab also studies how bacteria-infecting viruses enter
cells using this method, which could potentially lead to new antibacterial
treatments. Yet the world's best cryo-EM microscope costs more than $5 million.
Limited by funds but not drive, Parent was able to upgrade an existing
microscope at MSU to do cryo-EM -- one that is a tinkerer's dream.
This traditional transmission electron
microscope was retrofitted with a cryostage, which keeps viruses frozen in
liquid nitrogen while they're being studied. Parent and her team then added a
Direct Electron DE-20 detector, a powerful camera -- the mighty microscope's
piece de resistance.
Parent didn't invent cryo-EM, but
establishing it on campus serves as a viable proof-of-concept for MSU, opening
the door for many interdisciplinary partnerships. This cutting-edge microscopy
has applications across many fields, from those addressing a single protein to
others studying entire cells. Virtually anyone studying complex molecular
machines can advance their work with this tool, Parent added.
Parent has earned an AAAS Marion
Milligan Mason Award for Women in the Chemical Sciences. This award, her paper
in Viruses and being the co-author who performed cryo-EM work in a recent
Nature Communications paper, lays the groundwork to someday have a more
advanced cryo-EM microscope housed at MSU to be able to perform high-resolution
structural studies.
"We've done quite a bit with our
limited resources, but we're primed to do more," Parent said. "I
think MSU could serve as a cryo-EM center and to increase the prevalence of
this technology in the Midwest and beyond."
As one example, scientists from
Universidade Federal de Minas Gerais (Brazil) and Universidade Federal do Rio
de Janeiro (Brazil) also contributed to this study and benefitted from the
technology MSU has to offer.
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Posted by Dr. Tim Sandle
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