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Project 1: The development of more effective anti-cancer drugs based on cisplatin
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In collaboration with researchers at Melbourne University and Auckland University, NZ, we are developing more effective cancer chemotherapeutic agents based on cisplatin. The biological target for cisplatin is DNA but cisplatin has no intrinsic affinity for DNA. By attachment of a DNA binding group to cisplatin, it is hoped to specifically target cisplatin to DNA.
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Human telomeric sequences consist of the repeated sequence TTAGGG. The integrity of telomeres is believed to be very important in the development of tumour cells. Because telomeres contain a GGG repeat sequence, they are expected to be a major target site for cisplatin. The main aim of this project is to examine the interaction of newly synthesised cisplatin analogues with telomeric DNA inside cells. The techniques involved include human tissue culture, DNA sequencing, PCR, and other molecular biology techniques.
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Selected References (Available on request)
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Project 2: Mechanism of action of the anti-tumour drug cisplatin
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| The main aim of this research project is to investigate genes that are preferentially affected by the anti-tumour drug cisplatin. Cisplatin is widely used in the clinic as a cancer chemotherapeutic agent. However, its precise mechanism of action is not fully understood. The effect of cisplatin on the levels of transcription is a very important component of the mode of action of cisplatin. A previous PhD student has utilised microarrays to investigate the effect of cisplatin on the levels of transcription of 19,000 human genes. She identified several hundred genes that were upregulated or downregulated by cisplatin. It is proposed to investigate in detail a subset of these cisplatin-affected genes. In this way it is hoped to i) more fully understand the mechanism of action of cisplatin and ii) identify possible gene targets as mimics of cisplatin action. Progress with ii) could provide the basis for a nucleic acid therapy as a cancer chemotherapeutic agent. In this project RNAi will be utilised to gauge the importance of the cisplatin affected genes. |
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