Functional analysis of JAK/STAT signalling using genome-wide RNAi

• Applicant: Dr. Martin Zeidler
• Subject Area: Cell Biology
• Term: from 2005 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5446281

• Final Report Year: 2010

Final Report Abstract

We undertook genome wide RNAi screens to identify and characterise regulators of the JAK/STAT signal transduction pathway – a signalling cascade whose mis-regulation is a key factor in the development of many human cancers including a wide range of leukaemias. We describe the RNAi screen itself (published in Nature) as well as studies into pathway function that arose from this screen. These include an analysis of the role of endocytosis / trafficking on JAK/STAT signalling as well as a transcript profiling approach to identify cancer-relevant downstream factors. In addition, this support has contributed to the initial work required for the set up of the Wellcome Trust supported Sheffield RNAi Screening Facility.

Publications

• (2005). “Identification of JAK/STAT signalling components by genome-wide RNAi”. Nature 436 871-875
  Müller, P., Kuttenkeuler, D., Gesellchen, V., Zeidler, M.P. and Boutros M.
  
• (2008). ‘Identification of JAK/STAT pathway regulators - results from RNAi-based reverse genetic screens’. Seminars in Cell and Developmental Biology 19 360-369
  Müller, P., Boutros, M., Zeidler, M.P.
  
• (2008). “JAK/STAT pathway signalling in Drosophila melanogaster”. In: “JAK-STAT Pathway in Disease”, edited by Dr. Anastasis Stephanou, (2008 Landes Bioscience)
  Bina, S. and Zeidler, M.P.
  
• (2010). “Negative Regulation of Drosophila JAK/STAT signalling by endocytic trafficking”. J. Cell Sci Sep 14. [Epub ahead of print]
  Vidal, O-M., Bausek, N., Smythe, E., Zeidler, M.P.
  (See online at https://doi.org/10.1242/jcs.066902)
• (2010). “Transcriptional targets of Drosophila JAK/STAT pathway signalling as effectors of haematopoietic tumour formation”. EMBO Reports 11(3) 201-207
  Bina, S., Wright, VM., Fisher, KH., Milo, M., Zeidler, MP.