A COPAS BIOSORT Flow Cytometer for Caenorhabditis elegans Molecular Genetics

Greenstein, David

Abstract

A group of NIH-funded investigators proposes to acquire a COPAS BIOSORT flow cytometer to enhance their research on a wide range of biomedical problems. The nematode Caenorhabditis elegans has emerged as a major genetic model system for studying biological problems with direct relevance to human health, development, and disease. Researchers at the University of Minnesota are at the forefront of this field, and have the distinction of administering the Caenorhabditis Genetics Center, which is supported by the National Institutes of Health-National Center for Research Resources. Recent advances in instrumentation and fluorescent protein research have made C. elegans an even more powerful system for forward or reverse genetics and chemical biology for drug discovery. This application seeks to provide automated instrumentation to meet three key research objectives for researchers at the University of Minnesota. First, acquisition of a flow cytometer will dramatically quicken the pace of high-throughput phenotypic screening, genomic analysis, and biochemistry using C. elegans. This instrumentation will enable researchers to conduct for the first time fully automated screens using genetics, RNAi, and chemical biology. Second, this instrumentation will allow novel screens to be undertaken that would not otherwise be attempted. Finally, this instrumentation will foster collaborative interactions between members of the C. elegans community and local researchers in diverse fields by lowering the activation energy for entering the field. Automation eliminates key bottlenecks inherent in large-scale screening by (1) establishing large numbers of parallel cultures of precisely staged nematodes and (2) assessing multiple biological parameters from an array of experimental test conditions. What once took years, can now be accomplished in days with enhanced sensitivity using the flow cytometer. The COPAS BIOSORT flow cytometer is manufactured only by Union Biometrica in the United States. The COPAS BIOSORT has been installed in laboratories throughout the world;however, there is no such instrument in Minnesota. The requested instrument is needed so that researchers in the University of Minnesota system can continue their high level of productivity in C. elegans research with applications aimed at understanding (1) the control of germline development by cell signaling, (2) the regulation of developmental timing, (3) the mechanisms of sex determination, and (4) the function of cell adhesion in muscle and nervous system development. 11