Funding in the first three cycles of this grant provided support of the Drosophila RNAi Screening Center (DRSC) at Harvard Medical School, allowing us to bring to the community a unique state-of-the-art infrastructure for high-throughput RNAi screens (RNAi-HTS) in Drosophila cells. To date, we have facilitated many full-genome screens, smaller screens and other projects, resulting already in more than 125 publications on screen results, methods, meta-analysis, etc. Reagent information and screen datasets are available for search or download online at our own website, www.flyrnai.org, as well as at other sites such as FlyBase, GenomeRNAi and NCBI PubChem BioAssays. Over the years we have designed, generated, and refined our RNAi libraries and added libraries for over-expression screens and interrogation of miRNA function. Our RNAi libraries offer exceptional quality and coverage, comprising nearly 35,000 unique, high-quality double stranded RNA (dsRNA) reagents targeting a total of about 14,000 protein-coding and non-coding Drosophila genes. We also designed and maintain an extensive laboratory information management system (LIMS) and database, as well as a website that provides free access to protocols, publications, datasets, and an increasing number of online software tools. Altogether, we have succeeded in establishing ourselves as an integrated center for screening and technology transfer, serving the widest possible community of researchers. Through support of both on-site and off-site screens using our high-quality libraries, researchers are continuing to conduct innovative cell-based assays to address fundamental cell biological questions and disease-related topics, taking advantage of the efficiency, low gene redundancy and gene conservation offered by the Drosophila cell system. The experience we have gained since 2003 has shaped our view of how to further expand the scope and impact of the DRSC through continued support of on-site and off-site screening as well as rapid transfer of new technologies (e.g. CRISPR-Cas technologies) to the community. In this competing renewal, we seek continued support for the DRSC resource so we can keep providing the state-of-the reagents, experimental and informatics infrastructure that makes Drosophila functional genomic screening accessible to the widest possible group of researchers. Among the reasons our efforts are critical is that unlike for functional genomics studies in mammalian cells, commercial companies have no commitment to provide the community with reagents, databases and software tools for Drosophila functional genomics screens and analyses.

Public Health Relevance

This project aims to seek continued support for the Drosophila RNAi Screening Center (DRSC) at Harvard Medical School. We will continue to provide the community with state-of-the-art reagents and infrastructure for functional genomic screening in Drosophila cells. Moreover, we will continue to serve as a 'technology transfer center' by making protocols, reagents, equipment, software, etc. rapidly available to the community at large.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM067761-16
Application #
9598340
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Sledjeski, Darren D
Project Start
2003-05-01
Project End
2019-11-30
Budget Start
2018-12-01
Budget End
2019-11-30
Support Year
16
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Harvard Medical School
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
Ewen-Campen, Ben; Mohr, Stephanie E; Hu, Yanhui et al. (2017) Accessing the Phenotype Gap: Enabling Systematic Investigation of Paralog Functional Complexity with CRISPR. Dev Cell 43:6-9
Ewen-Campen, Ben; Yang-Zhou, Donghui; Fernandes, Vitória R et al. (2017) Optimized strategy for in vivo Cas9-activation in Drosophila. Proc Natl Acad Sci U S A 114:9409-9414
Sung, Eui Jae; Ryuda, Masasuke; Matsumoto, Hitoshi et al. (2017) Cytokine signaling through Drosophila Mthl10 ties lifespan to environmental stress. Proc Natl Acad Sci U S A 114:13786-13791
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

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