CA -- June 26, 2001 - A new high-throughput cell
analysis tool capable of measuring hundreds to
thousands of cellular properties simultaneously
has been developed by scientists at Biolog, Inc.,
who report their work in the July issue of the
journal Genome Research. The new Phenotype MicroArray
(PM) technology permits the study of a wide range
of cell properties (phenotypes) as a means of
understanding how a gene or a drug affects living
cells - a critical step in identifying new drug
targets and developing safe and effective new
Genome Research article describes the use of PMs
to determine the function of genes - one of the
most important applications of the new technology.
Researchers can use PMs to analyze gene function
by conducting a very detailed comparison of two
cell lines - one of which has been modified by
a genetic change - and directly measuring the
cellular response to that change. In Genome Research,
Biolog scientists report tests conducted in the
cell model bacterium E. coli. Using PMs, the scientists
were able to detect the expected changes in cellular
response, known as phenotypic changes, associated
with genes whose function was already known. More
importantly, the PMs were able to detect several
unexpected phenotypes as well, leading the researchers
to make new discoveries about gene function.
the recent explosion of genes sequenced, there
is a critical need to quickly, efficiently and
accurately characterize and sort through the thousands
of genes that are now proposed as potential drug
targets," said Barry Bochner, Ph.D., Biolog
chairman and vice president of research and development.
"By providing rapid and detailed answers
to how a gene of unknown function affects a cell
at the physiological level, Phenotype MicroArrays
can greatly accelerate the critical step of evaluating
potential drug targets. In addition, this technology
can help to protect biological discoveries, since
the ability to patent a gene depends on understanding
the function of that gene."
provide unprecedented speed and cost-effectiveness
in cell analysis. Scientists using conventional
methods are only able to test one phenotype at
a time, and they need to know beforehand which
phenotypes are important to test. PMs, on the
other hand, allow researchers to measure thousands
of phenotypes that may be important. Information
from PMs can indicate whether or not changes in
gene or protein expression are significant at
the cellular level. As such, PMs complement the
molecular information provided by DNA microarray
and proteomic technologies, which are also used
to study gene function.
are arrays composed of hundreds to thousands of
wells, each of which contains a chemistry designed
to test a different cellular property or pathway.
To use the array, the scientist simply introduces
a cell suspension into the wells. The response
of the cells in each well is monitored over a
specified period of time, producing quantitative
and kinetic data for each cell function test.
Incubation and recording of phenotypic data are
performed by Biolog's OmniLog® PM System,
which uses bioinformatic software to report changes
in specific cell functions.
developed its PM technology using its core expertise
in cell physiology, cell metabolism and color
chemistries that respond to cell respiration.
The result is a high-throughput assay system that
provides a colorimetric measurement of the cells'
breathing rate to indicate a specific response
to each of the phenotypes being tested. The Genome
Research article describes the use of this technology
to monitor about 700 cellular phenotypes, including
about 300 pathways of carbon, nitrogen, phosphorus
and sulfur metabolism, 100 biosynthetic pathways,
and 300 processes measured by increased or decreased
sensitivity of cells to toxic chemicals.
addition to gene function analysis, PMs can be
used to monitor the genetic stability of cell
lines used in research. In Genome Research, Biolog
scientists report that PMs were able to find previously
undetected phenotypes resulting from genetic changes
in E. coli cell lines received from other laboratories.
Therefore, PMs are an important tool for scanning
cell lines to verify expected changes, and to
detect and identify unknown changes and defects
that may affect the experimental results. Other
applications for PMs include validation and optimization
of drug targets, evaluation of a drug's mode of
action, and assessment of cell toxicology.
Currently the Phenotype MicroArray technology
is optimized for use with bacteria and fungal
cells. The company has developed a procedure that
facilitates analysis of the most important bacterial
infectious disease agents, and is well along in
parallel work on fungal pathogens. The company
is also developing PMs for mammalian cell lines.
Biolog, Inc. is a pioneer in the development of
innovative and cost-saving cell-based analysis
tools for solving critical challenges facing the
pharmaceutical and biotechnology industries. The
company's unique and powerful Phenotype MicroArray
technology and OmniLog® PM System are used
in drug discovery to determine gene function,
validate and optimize drug targets, as well as
assess cellular toxicology in many clinical applications.
In addition to its novel Phenotype MicroArray
technology, Biolog also offers tools for the identification
and characterization of microbes ranging from
bacteria to fungi. Further information can be
obtained at the company's website, www.biolog.com.