Transgenic Caenorhabditis elegans comprising a human protein with a tendency to aggregate fused to a fluorescent protein
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsStephen C. Pak, David H. Perlmutter, Gary A. Silverman
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Abstract
The present invention relates to methods and compositions for high content drug screening in Caenorhabditis elegans which may be used to identify compounds that treat disorders associated with protein aggregation. It is based, at least in part, on the discovery that Caenorhabditis elegans, genetically modified to create a model system for disorders of protein aggregation, could be used, in a high throughput screening system, to identify agents that reduce the amount of aggregated protein.
Claims16
A Caenorhabditis elegans whose genome comprises a first transgene comprising:
- (a) a nucleic acid encoding a first fluorescent protein and (b) a nucleic acid encoding a human protein with a tendency to aggregate, or a polymerizable portion thereof, operably linked to a first Caenorhabditis elegans promoter, wherein said nucleic acid encoding a human protein with a tendency to aggregate, or a polymerizable portion thereof, comprises one or more synthetic introns resembling Caenorhabditis elegans introns, wherein said one or more synthetic introns comprise an AGGUAAGU splice acceptor sequence, a CAGG splice donor sequence, or both;
- wherein the human protein with a tendency to aggregate, or a polymerizable portion thereof, is fused with the first fluorescent protein and is expressed as a fusion protein, and wherein the expression of the fusion protein results in a detectable accumulation of the human protein in the Caenorhabditis elegans.
Dependencies are inferred from the claim text.