The challenge generated by the various large scale genome projects is to derive biologically relevant information from the primary DNA sequences. In the past few years, a number of approaches to mine this information have emerged. These can be divided into Expression Genomics, Proteomics, Information Genomics, and Functional Genomics. Perhaps, the most promising Functional Genomics approach is based on the double strand RNA (dsRNA) methodology. In several organisms, introduction of a dsRNA has proven to be an effective tool to suppress gene expression through a process referred to as RNA interference (RNAi). Importantly, the simple addition of dsRNA to Drosophila cells in culture reduces or eliminates the expression of target genes by RNAi, thus phenocopying loss-of-function mutations. This property of Drosophila cells make it possible to develop high throughput RNAi screens in 384-well plates to efficiently and systematically test the function of all 14,000 Drosophila genes in specific cell-based assays. In the past few years, we have developed such a methodology and the goal of this proposal is to establish an infrastructure within the Institute of Chemistry and Cell biology at Harvard Medical School (ICCB/HMS) that will make this approach available to the entire community. Specifically, we propose to establish an """"""""RNAi facility"""""""" where visiting scientists will be hosted to conduct RNAi screens with help of experienced staff. The facility will provide bioinformatic support to help investigators conduct the screens and interpret the primary data. In addition, a central database will be established that keeps records of all RNAi screens. The results generated by the """"""""RNAi facility"""""""" will become a public database, and thus provide a discovery vehicle to generate hypothesis driven research. Finally, to demonstrate the value of the approach, we describe a number of cell-based screens that will identify genes involved in cell survival, cytokinesis, cell shape changes and immunity.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM067761-04
Application #
7046887
Study Section
Genome Study Section (GNM)
Program Officer
Tompkins, Laurie
Project Start
2003-05-01
Project End
2007-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
4
Fiscal Year
2006
Total Cost
$816,781
Indirect Cost
Name
Harvard University
Department
Genetics
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Sung, Eui Jae; Shears, Stephen B (2018) A genome-wide dsRNA library screen for Drosophila genes that regulate the GBP/phospholipase C signaling axis that links inflammation to aging. BMC Res Notes 11:884
Viswanatha, Raghuvir; Li, Zhongchi; Hu, Yanhui et al. (2018) Pooled genome-wide CRISPR screening for basal and context-specific fitness gene essentiality in Drosophila cells. Elife 7:
Hu, Yanhui; Vinayagam, Arunachalam; Nand, Ankita et al. (2018) Molecular Interaction Search Tool (MIST): an integrated resource for mining gene and protein interaction data. Nucleic Acids Res 46:D567-D574
Mohr, Stephanie E; Rudd, Kirstin; Hu, Yanhui et al. (2018) Zinc Detoxification: A Functional Genomics and Transcriptomics Analysis in Drosophila melanogaster Cultured Cells. G3 (Bethesda) 8:631-641
Jayson, Christina B K; Arlt, Henning; Fischer, Alexander W et al. (2018) Rab18 is not necessary for lipid droplet biogenesis or turnover in human mammary carcinoma cells. Mol Biol Cell 29:2045-2054
Housden, Benjamin E; Muhar, Matthias; Gemberling, Matthew et al. (2017) Loss-of-function genetic tools for animal models: cross-species and cross-platform differences. Nat Rev Genet 18:24-40
Song, Wei; Cheng, Daojun; Hong, Shangyu et al. (2017) Midgut-Derived Activin Regulates Glucagon-like Action in the Fat Body and Glycemic Control. Cell Metab 25:386-399
Housden, Benjamin E; Li, Zhongchi; Kelley, Colleen et al. (2017) Improved detection of synthetic lethal interactions in Drosophila cells using variable dose analysis (VDA). Proc Natl Acad Sci U S A 114:E10755-E10762
Hu, Yanhui; Comjean, Aram; Mohr, Stephanie E et al. (2017) Gene2Function: An Integrated Online Resource for Gene Function Discovery. G3 (Bethesda) 7:2855-2858
Hu, Yanhui; Comjean, Aram; Perrimon, Norbert et al. (2017) The Drosophila Gene Expression Tool (DGET) for expression analyses. BMC Bioinformatics 18:98

Showing the most recent 10 out of 84 publications