[tt] [biomed] wired: infrared equivalent of the GFP can help in seeing gene activity inside bodies

Sat May 9 17:11:00 CEST 2009

(
http://www.wired.com/wiredscience/2009/05/infraredcells/
)

Infrared Proteins Give Deep View Inside Living Animals

 * By Brandon Keim Email Author
 * May 7, 2009 | 
 * 2:06 pm | 
 * Categories: Miscellaneous

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A fluorescent protein found in an extremophile bacteria could give
scientists an unprecedented view inside living animals.

The proteins, which glow with tissue-penetrating infrared light, could
be used to tag cells in living animals, allowing researchers to watch
real-time biological processes that have until now been hidden.

“Because their wavelengths penetrate tissue well, infrared-fluorescent
proteins are suitable for whole-body imaging,” write University of
California at San Diego biochemists Roger Tsien and Xiaokun Shu in a
paper published Thursday in Science.

Tsien’s laboratory is best known for its work with green fluorescent
protein, or GFP, which helped make it possible to observe cellular
activity in detail as never before. GFP was originally discovered in
jellyfish by Japanese biologist Osamo Shimomura and first used to
illuminate cell activity by Columbia University neurobiologist Martin
Chalfie. Tsien pioneered the next step in GFP’s refinement, engineering
tens of thousands of markers that could be attached to any gene in the
body.

Nearly every paper now written on gene or cell function involves GFP,
either directly or by building on GFP-lit research. Its harnessing is
considered one of the great advances of modern science, arguably on par
with the development of the microscope — another tool that allowed
researchers to investigate a previously invisible world. Tsien,
Shimomura and Chalfie got the 2008 Nobel Prize in chemistry for their
work.

But for all its acclaim, GFP has its limits. The wavelengths of light it
emits and light used to observe this emission are quickly absorbed by
cells, making it difficult to study living cells except in laboratory
tissue cultures, microbes and extremely tiny animals. Those studies
reveal little of what might be discovered by watching living tissues in
complex organisms in real-time.

“The use of fluorescent proteins in intact animals, such as mice, has
been handicapped,” write Tsien and Shu.

Because infrared wavelengths pass easily through tissue, the new protein
could change that.

Tsien and Shu found the protein in Deinococcus radiodurans, an
extremophile microbe, that emits infrared light. The original protein
was relatively dim, but they tweaked its amino acid content to make it
brighter. They then injected mice with infrared proteins that attached
to genes in their liver cells.

Using a specialized microscope called a fluorescence molecular
tomograph, which assembles three-dimensional images from two-dimensional
scans taken at different depths in a target specimen. The liver shells
showed up, glowing through layers of living tissue.

Infrared protein imaging isn’t nearly as refined as GFP imaging, but
according to Tsien and Shu, another 1,500 proteins similar to their own
have already been identified. These could provide researchers with raw
material for further refinements, with infrared proteins lighting up
entire organisms as completely as GFPs have individual cells.