Identification and validation of target genes in cancer using the synthetic lethality approach
Supervisor(s): Dr Spiros Linardopoulos
Section: Breakthrough Breast Cancer Research Centre
Team: Drug Target Discovery
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Summary
The development of RNAi libraries, which are composed of reagents that allow the selective silencing of specific transcripts, has made it possible to conduct high-throughput screens (HTSs) that interrogate phenotypes associated with the loss of function of many genes [1]. Furthermore, siRNA libraries have been used to identify key determinants of resistance to chemotherapeutic drugs such as paclitaxel [2, 3]. We will use a library of synthetic siRNA oligonucleotide pools targeting the expression of the human “druggable” genome to identify those genes that, when silenced, cause lethality to cancer cells in vitro.
References
Lorns, E., et al.(2007) Utilizing RNA interference to enhance cancer drug discovery. Nat. Rev. Drug Discov Vol 6 Vol 7, p556–568
Whitehurst, W.A., et al. (2007) Synthetic lethal screen identification of chemosensitizer loci in cancer cells. Nature Vol 446(7137) p815–819
Swanton, C., et al. (2007) Regulators of mitotic arrest and ceramide metabolism are determinants of sensitivity to paclitaxel and other chemotherapeutic drugs. Cancer Cell Vol 11, No 6, p498–512
