One of the most striking findings revealed from the sequencing of genomes is the amount of information that we are currently missing on the discrete functions of genes. Drosophila is arguably the best-understood multi-cellular organism and a proven model system for human diseases. Nevertheless, mutations with readily detectable phenotypes have been isolated for only about 15% of the more than 15,000 annotated fly genes.

Our lack of functional information on the majority of genes (the "phenotype gap") does not indicate that these genes have no function. Instead, it indicates that we have been unable to either assay their roles experimentally or resolve an issue of functional redundancy. In addition, our understanding of a large fraction of "known" genes is limited by pleiotropy, whereby the earlier function of a gene prevents its functional analysis at later developmental stages.

Using transgenic RNAi it is now possible to disrupt the activity of single genes with a spatial and temporal resolution that is impossible or exceedingly difficult to achieve using classical genetic methods. With the backing of the NIH/NIGMS, the Drosophila Transgenic RNAi Project, or TRiP, has the goal to generate 6,250 transgenic RNAi lines designed to fill in the phenotype gap and help researchers overcome issues associated with pleiotropy.

Specifically, using a new approach for transgenic RNAi that relies on phiC31-targeted integration combined with the Gal4/UAS system, conditional and tissue-specific expression of hairpin constructs in Drosophila will be generated.

All validated transgenic fly lines will be made available to the entire community through the Bloomington Drosophila Stock Center (BDSC). The collection will be invaluable to address a myriad of questions in biology and medicine, including but not limited to cell biology, signal transduction and cancer, the etiology of congenital malformations, neurodegeneration, and behavior.

Already, a "proof of principle" project supported by the HHMI/Janelia Farm Visitor Program, has generated nearly 1,250 hairpin lines. Starting as early as Fall 2008 these lines will be available through the BDSC. At the same time and thanks to the NIH/NIGMS award, the TRiP will continue production and transfer of RNAi lines at a rate of 1,250 per year for the four years of NIH/NIGMS support.

Genes to be targeted will be selected based on the BDSC mandate of one mutation per gene, the needs of screeners at the Drosophila RNAi Screening Center (DRSC), and the needs of the Drosophila community for in vivo phenotypic analyses. This resource will be built, established and validated in the TRiP facility at Harvard Medical School and transferred to the BDSC for distribution.

Markstein M, Pitsouli C, Villalta C, Celniker SE, Perrimon N. Exploiting position effects and the gypsy retrovirus insulator to engineer precisely expressed transgenes. Nat Genet. 2008 Mar 2; [Epub ahead of print]

Ni JQ, Markstein M, Binari R, Pfeiffer B, Liu LP, Villalta C, Booker M, Perkins L, Perrimon N. Vector and parameters for targeted transgenic RNA interference in Drosophila melanogaster. Nat Methods. 2008 Jan;5(1):49-51. Epub 2007 Dec 16.

Genes to be targeted will be selected based on the Bloomington Drosophila Stock Center (BDSC) mandate of one mutation per gene, the needs for screeners at the Drosophila RNAi Screening Center (DRSC), and the needs of the Drosophila community for in vivo phenotypic analyses.

To nominate a gene(s) to be added, the PI of the lab should send a letter to TRiP@flyrnai.org that includes an explanation of why the specific gene(s) are being nominated.

Please note: The TRiP is an NIH/NIGMS funded endeavor with the goal of generating a genome-scale collection of 6,250 transgenic RNAi lines designed to fill in the phenotype gap and overcome issues associated with gene pleiotropy. Nominations are subject to review. All validated transgenic RNAi lines generated by the TRiP will be made available to the entire community i.e. nomination does not mean that your lab has priority access to a resulting transgenic RNAi line.