Analysis of Quadruplex Function in the Genome

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DNA is presumed to exist largely as the Watson-Crick double helix in living cells. There is growing evidence to suggest that the folded structure of DNA is dynamic and that alternative structural forms can exist and have function. A four-stranded form of DNA / a quadruplex helix called a G-quadruplex / that is known to form in certain G-rich sequences of DNA is likely to exist in many different places in our chromosomes. There is evidence to support that the formation of the quadruple helix can switch 'off' certain genes. This proposal aims to explore this hypothesis along with the chemical possibility of designing molecules that selectively stabilise such quadruple helix structures, and by doing so affect the function of certain genes. This would represent a new and exciting way to alter biological function by directly controlling genes. Given that genes form the basis for normal function and also for disease, the overall aims of this programme has the potential to inspire new therapeutic approaches to address human diseases and conditions by selectively targeting DNA structures, rather than proteins.