Funding in the first two 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 more than 100 full- genome and smaller screens, resulting already in 72 publications on screen results, methods, meta-analysis, etc. DRSC datasets are available for search or download online at our own website, www.flyrnai.org, as well as at other sites such as FLIGHT, GenomeRNAi, FlyMine and most recently, NCBI PubChem BioAssays. Importantly, over the years we have designed, generated, and refined our libraries of double-stranded RNAs (dsRNAs). Our libraries offer exceptional quality and coverage, currently comprising a total of nearly 33,000 unique, high-quality RNAi reagents targeting about 13,500 protein-coding and 400 non-coding Drosophila genes. We also designed and maintain an extensive laboratory information management system (LIMS) and database to track reagents, results, gene information, and more, as well as a website that provides free access to protocols, publications, datasets, software tools, and more. 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 screening using our high-quality libraries, researchers have and are continuing to conduct innovative cell-based assays interrogating diverse functions, such as cell growth, division and death, host-pathogen interactions, signal transduction, cell and organelle size and morphology, and much more. The experience we gained over the past eight years 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 to the community. In this competing renewal, we seek continued support for the DRSC to keep providing a state-of-the art infrastructure and reagents for functional genomic screening by the widest possible group of researchers. Our effort is critical as, unlike for RNAi screening in mammalian cells, commercial companies have no commitment to provide the community with reagents for Drosophila RNAi screens.

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 #
5R01GM067761-11
Application #
8582556
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Sledjeski, Darren D
Project Start
2003-05-01
Project End
2015-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
11
Fiscal Year
2014
Total Cost
$703,523
Indirect Cost
$288,465
Name
Harvard University
Department
Genetics
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Helenius, Iiro Taneli; Nair, Aisha; Bittar, Humberto E Trejo et al. (2016) Focused Screening Identifies Evoxine as a Small Molecule That Counteracts CO2-Induced Immune Suppression. J Biomol Screen 21:363-71
Zanotto-Filho, Alfeu; Dashnamoorthy, Ravi; Loranc, Eva et al. (2016) Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human. PLoS One 11:e0153970
Helenius, Iiro Taneli; Haake, Ryan J; Kwon, Yong-Jae et al. (2016) Identification of Drosophila Zfh2 as a Mediator of Hypercapnic Immune Regulation by a Genome-Wide RNA Interference Screen. J Immunol 196:655-67
Hu, Yanhui; Comjean, Aram; Roesel, Charles et al. (2016) FlyRNAi.org-the database of the Drosophila RNAi screening center and transgenic RNAi project: 2017 update. Nucleic Acids Res :
Mohr, Stephanie E; Hu, Yanhui; Ewen-Campen, Benjamin et al. (2016) CRISPR guide RNA design for research applications. FEBS J 283:3232-8
Vinayagam, Arunachalam; Kulkarni, Meghana M; Sopko, Richelle et al. (2016) An Integrative Analysis of the InR/PI3K/Akt Network Identifies the Dynamic Response to Insulin Signaling. Cell Rep 16:3062-74
Wang, Huajin; Becuwe, Michel; Housden, Benjamin E et al. (2016) Seipin is required for converting nascent to mature lipid droplets. Elife 5:
Sopko, Richelle; Lin, You Bin; Makhijani, Kalpana et al. (2015) A systems-level interrogation identifies regulators of Drosophila blood cell number and survival. PLoS Genet 11:e1005056
Dopie, Joseph; Rajakylä, Eeva K; Joensuu, Merja S et al. (2015) Genome-wide RNAi screen for nuclear actin reveals a network of cofilin regulators. J Cell Sci 128:2388-400
Ryu, Taehyun; Spatola, Brett; Delabaere, Laetitia et al. (2015) Heterochromatic breaks move to the nuclear periphery to continue recombinational repair. Nat Cell Biol 17:1401-11

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