Discovering New Drugs on the Cellular Level

As a potential source of food for long-duration space missions, space-grown plants could give astronauts an important psychological boost, as fresh vegetables could serve as a welcomed change from 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 Biolog (Hayward, CA), NASA is studying the impacts of decreased gravity and space-borne bacteria on the plants being grown for food in space. Biolog also is creating powerful new cell- and bacteria-analysis tools for use in discovering and developing new drugs on Earth.

From 1993 to 1997, 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. NASA 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.

Biolog extended the technologies to bring two novel and important cell-testing technologies to market: the Phenotype MicroArray and the OmniLog System.

How it Works

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, 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.

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. With the technology, an information- rich fingerprint of a drug’s effect on the cell under a wide range of physiological states can be obtained.

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.

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. Where it Stands The principal customers for Biolog’s 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. The U.S. Food and Drug Administration and the U.S. Department of Agriculture are employing the technologies to better understand food-borne pathogenic bacteria and the spread of epidemics.

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.