New Screening System Dramatically Speeds Drug Discovery Process Utilizing Nematode Worms

Replacing Labor Intensive Manual Sorting Could Provide Breakthroughs in Studies of Aging and Disease

September 8, 2003 Scientists at the Buck Institute for Age Research have developed a rapid, automated screening process to determine the effect of chemical compounds on the survival of the nematode Caenorhabditis elegans (C. elegans).  The new technology allows scientists to screen easily many thousands of compounds for their effect on the lifespan of the widely used roundworm, which shares many essential biological characteristics with humans. The system could replace the labor-intensive manual sorting process currently in use in laboratories around the world.

“It takes an experienced researcher about 20 minutes to manually screen about 200 worms,” said Buck Institute scientist Matthew Gill, PhD,  “Now we’re able to determine the viability of 384 worms in just 30 seconds.”   The patent pending system combines automated worm handling technology with automated real time fluorescent dye detection in an array-based format.  The methodology employed by the Buck Institute scientists is reported in the September 15th issue of Free Radical Biology and Medicine.

The microscopic roundworm is a popular organism for research because it follows essentially the same aging process as humans, yet lives for just 20 to 30 days.  In 2000, while working at the University of Manchester in the U.K., Gordon Lithgow, PhD,  (who now leads the Buck Institute laboratory where the new system was developed) and Buck scientist Simon Melov, PhD, used an experimental drug to significantly increase the lifespan of C. elegans. The lifespan increase is considered by many commentators to be the first time a drug was used successfully to boost an animal’s lifespan. Lithgow said it took a year and a half to gather study data for that experiment which was based on the use of just one chemical compound. “In my lab we now have the potential to test thousands of chemicals in that same time frame; this system removes the ceiling on our research efforts,” Lithgow said.

The new process utilizes the COPAS BIOSORT system, manufactured by Union Biometrica, Inc., and the fluorescent dye SYTOX green, produced by Molecular Probes Inc., in conjunction with a plate reading fluorometer from Thermo Electron Corporation. The BIOSORT system dispenses individual worms into 384-well microtiter plates containing the dye. Dead animals take up the SYTOX dye and the subsequent fluorescent signal can be detected by the fluorometer. In order to expedite the discovery of compounds that affect lifespan, the Buck Institute scientists have focused on assessing survival in response to acute stress, which has been shown to be an accurate indicator of natural lifespan in worms.

The authors of the paper include Matthew Gill, PhD, Anders Olsen, PhD, James Sampayo, PhD, and Gordon Lithgow, PhD, all scientists at the Buck Institute. The COPAS BIOSORT system was funded by a gift from the Glenn Foundation for Medical Research and the Herbert Simon Family Foundation.  Additional support came from a Brookdale National Fellowship to Matthew Gill, the Danish Research Council and an Ellison Medical Foundation Senior Scholar Award.

The Buck Institute for Age Research is a non-profit organization that conducts clinically relevant research into the biology of aging and age-related diseases such as cancer, stroke, Alzheimer’s and Parkinson’s.  Its mission is to extend the healthy years of life through basic research. At the Institute, a multi-disciplinary group of researchers uses state-of-the-art technologies to understand why we age, and to seek ways to delay or prevent age related diseases.  The Buck Institute is the only free standing institute devoted to age research in the United States, and one of only three in the world.  It is located 20 miles north of San Francisco.

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