Toxic compounds are a major health hazard in our environment, in our food, and in our pharmaceuticals. Identifying toxic compounds is currently time-consuming, expensive and complicated by animal rights issues. We propose to generate a set of 96 transgenic nematodes that will contain fluorescent constructs that can measure activation of specific pathways. These strains can be used to categorize the molecular activity of novel compounds - that is, what cell biological process is affected by the presence of these compounds. The reporter constructs will consist of promoters for the main toxic response pathways and the major developmental signaling pathways fused to GFP. These constructs will be inserted into the genome as single- copy transgenes into a fixed chromosomal position. Insertion at this site is permissive for expression in all tissues and is not subject to silencing or alterations by recombination. The biosensor constructs will cover all of the main toxin response pathways such as oxidative degradation, transport, and sequestration, as well as the developmental pathways that might be activated by teratogens. The worms will be aliquoted in a 96-well plate format and frozen. It is anticipated that these strains will provide a stable biosensor panel available for use by different organizations that need toxicological profiling.
* information listed above is at the time of submission.