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DRSC
>> About Us
>> Funding
The Drosophila RNAi Screening Center is principally
funded by a grant from
the National Institute of
General Medical Sciences, a division of
the National Institutes of
Health. The project was launched with seed funds
from Howard Hughes Medical
Institute and Harvard
Medical School. The DRSC is also participating in the
collaborative Dana
Farber/ Harvard Cancer Center (DF/HCC) RNAi Core. The
DF/HCC is an NCI designated Comprehensive Cancer
Center.
Current Grants
NIGMS 2R01GM067761-05:
"Functional Genomic analysis using RNAi screen in
Drosophila"
Funding Period: 5/01/03 - 4/30/11
Grant Summary:
Funding provided in the first cycle
of this grant helped to establish at Harvard Medical School
the Drosophila RNAi Screening Center (DRSC). The purpose of
the facility was to provide the community with a unique
infrastructure and expertise for high-throughput RNAi screens
(RNAi HTS) in Drosophila cell lines using a genome-wide
collection of double stranded RNAs (dsRNAs). The DRSC has been
a resounding success. In less than 3 years, 75 applications
from 43 different institutions have been approved by the
center, 47 screens have been completed and 11 primary papers
detailing the screens have been already published. The vast
experience gained during these first years has been
instrumental in shaping our view on how to build upon our
initial goals and expand the scope and technology of RNAi HTS
in Drosophila. To face those new challenges and develop the
DRSC into an integrated center for technology transfer in
functional genomics, we propose the following: First, the
off-target effects observed with long dsRNAs will be addressed
through a re-design of our library and the ability to offer
two or more dsRNAs to confirm the specificity of RNAi
phenotypes. Second, we will implement a number of key
improvements to expand the range of functional screens
available at the DRSC. We will offer sub-collections of dsRNAs
against a variety of large gene families such as transcription
factors or cytoskeletal proteins for more focused screens, and
add miRNA and cDNA constructs over-expression libraries for
gain of function studies in Drosophila cell- based
assays. Third, to meet the growing demand on performing more
sophisticated screens with greater biological relevance, we
have added the ability to perform RNAi HTS in primary
Drosophila cell cultures and have acquired an ultra
high-throughput confocal, imaging platform that will be ideal
for high content imaging screens. Fourth, we address the need
of screeners to handle vast amount of data and the challenge
to analyze them by planning a major upgrade of our database
and developing powerful computational approaches for data
analysis and data mining. Lastly, we provide two practical
solutions to validate the results of the primary RNAi screen:
the ability to perform focused RNAi screens in mammalian cells
with siRNAs targeting human orthologs of genes identified in
the Drosophila screen, and the generation of custom short
hairpin RNA transgenic flies for rapid in vivo
validation.
NIGMS 1R01GM084947-01:
"Drosophila Transgenic RNAi Resource
Project"
Grant Summary:
In Drosophila, arguably the best-understood
multicellular organism and a proven model system for human
diseases, less than half of the 15,185 annotated genes have
mutations, and many fewer have readily detectable
phenotypes. Our lack of functional information on the
majority of the genes, also referred to as the "Phenotype
Gap", does not indicate that these genes have no function
but rather that, as experimentalists, we have been unable
to either assay their roles or resolve the issue of
functional redundancy. Conditional expression of hairpin
constructs in
Drosophila has emerged in recent years as the method
of choice to fill in the "Phenotype Gap", as well
as to overcome the issues associated with gene
pleiotropy. 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 using classical genetic methods. Here, we propose
to build a resource of 6,250 transgenic RNAi lines, the
"Transgenic RNAi Resource Project", using
improved methodology developed in our laboratory. The lines
will be established and validated at the Drosophila
RNAi Screening Center (DRSC) and transferred to the
Bloomington Drosophila Stock Center (BDSC) to be
made freely available to the community. We anticipate this
resource to be built, tested and transferred in its
entirety to the BDSC over a four-year period. This
collection of transgenic RNAi lines 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, neurodegenerative studies, and behavior.
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