Advanced Phenotypic Analysis

For Immediate Release
Tuesday, June 26, 2001
Contact:  Tim Mullane Carole Melis
  Biolog, Inc. CLM Communications
  (510) 785-2564 ext. 319 (650) 342-5686
Biolog Reports New High-Throughput Cell Analysis Tool for Gene Function Testing in Genome Research
Phenotype MicroArrays™ Can Test Thousands of Cell Properties Simultaneously

Hayward, 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 drugs.

The 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.

"Given 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."

PMs 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.

PMs 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.

Biolog 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.

In 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,

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