TRANSFOG
TRANSlational and Functional Onco-Genomics
Sixth_Framework
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Partner 5: NKI
Partner name: Nederlands Kankerinstituut/ Antoni van Leeuwenhoek ziekenhuis
Short name: NKI
Country: Netherlands
Role: CR (contractor)

This group has designed a mammalian expression vector that directs the synthesis of siRNA-like transcripts (pSUPER, suppression of endogenous RNA). We have successfully used this vector to stably suppress expression of more than one hundred different genes with no associated toxicity. As part of our contribution to the EuroFOG program, we will use this vector system to generate a large collection of some 6,000 siRNA vectors that each targets a single gene, specifically focussed on ESTs and poorly characterised genes. This collection of siRNA vectors will allow us for the first time to perform large-scale screens for loss-of-function phenotypes. The vector set will be shared with the other members of the TRANSFOG consortium to carry out genetic screens in pathways of their interest. NKI will be coordinator of WP3, aimed at generating the siRNA collection.

PERSONNEL
NAME
Title
Sex
Relevant Expertise
Rene Bernards Dr M PI , Molecular Oncology, Oncogenomics
Thijn Brummelkam MR M Generated pSUPER RNAi vector
Katrien Berns DR F helped built human RNAi library
Annette Dirac DR F helped built human RNAi library
Sebastian Nijman MR M generated proof-of-concept RNAi library
REFERENCES:
  • Peeper et al., 2002. A functional screen identifies hDRIL1 as an oncogene that rescues RAS-induced senescence. Nature Cell Biology 4, 148-153.
  • Shvarts et al., 2002. A senescence rescue screen identifies BCL6 as an inhibitor of antiproliferative p19ARF-p53 signalling. Genes, Dev. 16, 681-686.
  • Brummelkamp et al., 2002. A system for stable expression of short interfering RNAs in mammalian cells. Science 296, 550-553.
  • Brummelkamp, T.R., Bernards, R and Agami, R. (2002). Stable suppression of tumorigenicity by virus-mediated RNA interference. Cancer Cell 2, 243-247.
  • Van de Vijver et al., 2002. A gene expression signature as a predictor of survival in breast cancer. New England J. Med. 347, 1999-2009.
UPCOMING EVENT
OECI week

OECI Week (WG workshops; Scientific Conference and General Assembly) – Budapest, 16 to 18 June 2010.
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