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Research project: Roach: DNA Methyltransferases

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DNA adenine methylation plays an important role in several critical bacterial processes including mismatch repair, the timing of DNA replication and the transcriptional control of gene expression.

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The virulence of some bacteria (i.e. their ability to cause disease) is dependent on presence of functional DNA adenine methyltransferase (Dam), and this has led to the proposal that selective Dam inhibitors might function as broad spectrum antibiotics.

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We have developed a novel high throughput, real time fluorescence based assay that can be used to screen for Dam inhibitors in a 384 well format. Automation using a laboratory robot is used to further speed up the high throughput screening process.

Working in collaboration with Prof. Petra Oyston at DSTL Porton Down, we are synthesizing libraries of potential Dam inhibitors and screening them for selective inhibition of Y. pestis Dam. We are also investigating the application of our assay design to other methyltransferases, other DNA modification and repair enzyme.

Wood, R. J., M. D. Maynard-Smith, V. L. Robinson, P. C. Oyston, R. W. Titball and P. L. Roach (2007). "Kinetic analysis of Yersinia pestis DNA adenine methyltransferase activity using a hemimethylated molecular break light oligonucleotide." PLoS ONE 2(8): e801.

Related research groups

Chemical Biology, Diagnostics and Therapeutics
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