Hayward, CA - March 24, 2011 – In a paper published today in the journal PLoS ONE,
researchers from Biolog, Inc., and the Broad Institute of Harvard & MIT describe the successful
application of redox-based assays to study the growth properties of mammalian cells. The
technology, termed Phenotype MicroArray™ (PM), comprises a panel of cell assays providing a
colorimetric readout of diverse energy-producing pathways in any type of animal cell. Energy is
needed to drive virtually all cellular processes, including growth, differentiation, stress responses,
and responses to drugs and other small molecules.
To generate energy, cells have multiple enzymatic pathways for producing NADH, which can then
be converted to ATP and other useful forms of energy. Scientists at Biolog, Inc. developed new
redox dye chemistries that yield a purple color as cells generate NADH. Over a few hours, the
assay measures the rate at which cells are generating NADH without harming the cells. Data
from seven different cancer cell lines shows that each utilizes different sets of energy-producing
pathways. Most energy-producing pathways in cells use mitochondria to produce NADH, and the
authors show that small molecules that poison mitochondria also block color formation in those
pathway assays.
Bridget Wagner and Paul Clemons, scientists at the Broad Institute, used PM technology to
compare metabolism in fat-storing adipocytes. Mammals have two types of adipocytes: brown
adipocytes generate heat to maintain body temperature, and have been shown to be
developmentally related to muscle cells. More abundant white adipocytes store excess calories in
the form of lipids. Wagner and Clemons used PM technology to analyze energy pathways in
these cell types and their precursor “preadipocytes”, and found numerous metabolic differences.
Such differences can be exploited in attempts to selectively culture stem or precursor cells, or
mature, differentiated cell forms.
According to Barry Bochner, CEO & CSO at Biolog, “The PM assay is really measuring a flow of
electrons. The electrons originate from the substrates that the cell is metabolizing, are passed
along to NAD or NADP, and then to the redox dye. Although this is a metabolic assay, it is quite
different from other metabolic assay approaches such as metabolomics, which measures pool
levels of metabolic intermediates, but is difficult to use for measuring pathway activity or flux.
Measurement of pathway flux is typically done with radioactive tracers, which is complex,
expensive, and requires that all pathways are known to correctly interpret the data. PM assays
can elucidate unknown pathways and be performed by any laboratory.”
A major advantage of PM technology is its simplicity. Even small differences can be accurately
detected. An example described in the paper is the metabolic differentiation of the HepG2/C3A
cell line from its precursor cell line, HepG2. Furthermore, it is useful in a wide range of studies.
In cancer research, PM technology can be used to study the Warburg effect and the relationship
between changes in oncogenes and changes in metabolism. In diabetes and obesity, shifts in
energy metabolism are important for when and how cells burn or store calories. Energy
metabolism changes are also fundamental to understanding chemical toxicity, mitochondrial
dysfunction and aging. Additionally, PM technology can be a productive tool for optimizing
industrial bioprocesses where cells use energy to grow and produce a desired product.
Phenotype MicroArray technology, initially developed with SBIR funding from NIH, is proving to
be an important profiling technology. It allows scientists to study the growth properties and culture
condition responses of bacterial, fungal, and even human cells. As such it is becoming a core
technology for many cellular studies.
About Biolog:
Biolog is a privately held company based in Hayward, CA, that continues to lead in the
development of powerful new cell analysis tools for solving critical problems in biological,
pharmaceutical, and biotechnological research and development. It is the world leader in
phenotypic cell profiling. Biolog’s assay technology is unique in its broad applicability to cells –
this includes bacterial cells and fungal cells as well as animal cells. More than 200 scientific
publications and presentations document the effectiveness and productivity of PM technology.
The PM product line adds to the innovative microbial identification products offered by the
company, such as the new GEN III System. Biolog products are available worldwide, either
directly from the company or through its extensive network of international distributors. Further
information can be obtained at Biolog's website, www.biolog.com. |
