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Discovering
New Drugs on the Cellular Level
Health and Medicine
Originating
Technology/ NASA Contribution
With the Vision for Space Exploration calling for a
sustained human presence in space, astronauts will
need to grow plants, while in orbit, for nourishment
that they will not receive from only consuming dehydrated
foods. As a potential source of food for long-duration
missions, space-grown plants could also give astronauts
an important psychological boost, as fresh vegetables
could serve as a welcomed change from monotonous meals
consisting of reconstituted foods in plastic bags.
Even more, these plants could likely aid in the recycling
of air and wastewater on spacecraft.
With a helping hand from a company by the name of Biolog,
Inc., NASA is studying the impacts of decreased gravity
and spaceborne bacteria on the plants being grown for
food in space.
With a helping hand from NASA, this very same company
is creating powerful new cell- and bacteria-analysis
tools for use in discovering and developing new drugs
on Earth.
Partnership
From 1993 to 1997, Hayward, California-based Biolog
received Phase I and II Small Business
Innovation Research (SBIR) contracts from Kennedy Space Center to work
with NASA in developing two technologies that are now
in use by Biolog customers worldwide. The first technology,
based on the company’s pre-existing assay kits, was
a process created to monitor populations of microbes.
Dr. Jay Garland, manager of the Life Support Group
at Kennedy, was interested in using this process as
a way of monitoring the health of hydroponic crops
that would be grown in space during future manned missions
to Mars. The second technology was an instrumented
system that would allow automated monitoring of Biolog’s
assay kits for NASA’s purposes. Together, these innovations
intended to provide NASA with better means of growing
food in space and avoiding a catastrophic crop failure
during long-term space travel.
Product Outcome
Biolog went on to extend the technologies it developed
with SBIR assistance from NASA in order to bring two
novel and important cell-testing technologies to market:
the Phenotype MicroArray and the OmniLog System.
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Biolog,
Inc.’s product lines have been built upon patented
technology that greatly simplifies testing
of cells. Principal customers include pharmaceutical,
biotech, and cosmetic laboratories, as well
as laboratories testing for human, animal,
and plant diseases. |
Biolog’s Phenotype MicroArray technology is complementary
to DNA microarrays and proteomic technologies, which
allow scientists to detect changes in levels of genes
or proteins that direct most cellular functions. By
measuring the patterns of change in genes and proteins,
scientists are attempting to correlate the findings
with something important, such as a disease state.
A major goal would be to understand the biochemical
basis underlying a disease and gain insight into how
to correct the problem. However, according to Biolog,
there are typically hundreds to thousands of changes
that are detected by these gene and protein analyses
and it is often difficult to judge which ones are really
significant to the cell.
“A big advantage we have with our Phenotype MicroArray
cellular assays is that we are measuring change at
the cellular level,” claimed Dr. Barry Bochner, Biolog
chairman and chief scientific officer. “Proteomics
and gene expression don’t necessarily give enough insight—often,
you don’t really know what it means to the cell. The
data we get is at a higher level in terms of information
content and can be simpler to interpret.
”
Because of this, the Phenotype MicroArray represents
the third major technology that is needed in the genomic
era of research and drug development, according to
the company. Just as DNA microarrays and proteomic
science have made it possible to assay the level of
thousands of genes or proteins all at once, the Phenotype
MicroArray technology makes it possible to quantitatively
measure thousands of cellular traits (phenotypes) simultaneously,
in both microbial and mammalian cells. Such measurements
can be critical in determining the effects of genetic
changes and drug exposure on cells.
In the field of drug discovery, the Phenotype MicroArray
allows researchers to obtain a comprehensive picture
of a drug’s effect on a specific cell. “People usually
do this type of assay on cells in a rapid growth state,
and they’re only looking at the cell under one state,”
Bochner noted. “But a cell is always changing. With
our technology, you can take a drug and get a very
information-rich fingerprint of its effect on the cell
under a wide range of physiological states.”
Incubation and recording of phenotypic data gathered
from the Phenotype MicroArray are performed by the
OmniLog PM System, an integrated system of cellular
assays, instrumentation, and bioinformatics software.
Just as it automatically monitored assay kits for NASA,
the OmniLog technology monitors thousands of phenotypes
simultaneously. Several times each hour, it captures
digital images of the cell assays being studied and
stores quantitative color change values as computer
files. These files can be displayed in the form of
kinetic graphs
and up to 480,000 data points can be generated in a
24-hour period.
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A
Biolog, Inc., laboratory technician performs
cellular tests using Phenotype MicroArray assays
and the OmniLog System. The technology is capable
of monitoring thousands of phenotypes simultaneously. |
Another version of the OmniLog product, called
the OmniLog ID System, can be paired with Biolog’s
microbial-identification kits to easily and efficiently
identify over 2,000 species of aerobic and anaerobic
bacteria, yeasts, and fungi, virtually everything from
A to Z (Achromobacter cholinophagum to Zygosporium
mycophilum).
The principal customers for Biolog’s Phenotype MicroArray
and OmniLog products are laboratories requiring state-of-the-art
capabilities in cell-based assay and identification
products, especially pharmaceutical, biotech, cosmetics,
and medical device companies;
university and government research laboratories; laboratories
testing for diseases of humans, animals, and plants;
laboratories performing environmental monitoring; and
companies or organizations involved in production or
testing of food and drink.
Applications of the NASA-funded technology continue
to expand and evolve. Biolog recently announced that
the Phenotype MicroArray and OmniLog products have
been installed at the Lawrence Livermore National Laboratory,
in Livermore, California, where genomics researchers
are using the technology to understand and characterize
phenotypes of bacteria strains that are considered
potential bioterrorism agents. Other important government
laboratories such as the U.S. Food and Drug Administration
and the U.S. Department of Agriculture are also employing
the technologies to better understand foodborne pathogenic
bacteria and the spread of epidemics.
Additionally, Biolog is sharing its innovations with
the Nara Institute of Science and Technology, in Japan,
in an effort to broaden what is known about the functions
of genes in the important bacterium E. coli. According
to Tim Mullane, Biolog president and chief executive
officer, “E. coli is one of the most studied model
cell lines in the world, and despite the early sequencing
of this organism’s genome, many of its 4,000 genes
have no known function. Even where function is known,
this information is often incomplete.”
Next on the list for Biolog is to broaden the technologies
for use with human cells. The company will soon be
releasing Phenotype MicroArrays that can assess the
energy metabolism pathways in cells from different
organs and tissues. This should aid studies in diabetes,
obesity, and cancer.
Phenotype MicroArray™ is a trademark
of Biolog, Inc.
OmniLog® is a registered trademark of
Biolog, Inc
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