Design, Optimisation and Validation of High Density Microarrays for Multiple Escherichia Coli Genomes

The proposal builds on our successful 'Exploiting Genomics' (ExGen) programme to ensure that next generation microarray technology and expertise remains available and accessible to the research and applications communities. <P>
Spotted oligonucleotide microarrays have been a key resource that has enabled major progress to be made in functional genomics of Escherichia coli in our ExGen programme, but it is now clear that they have peaked in their development and applications. Technical advances and falling costs in in situ fabrication of microarrays provide unparalleled flexibility and resolution that cannot be matched by oligo printing. <P>We propose to build on work pioneered by the Busby group and ExGen team at U of B in collaboration with Oxford Gene Technology (OGT), to develop new, versatile and broadly applicable next-generation arrays for both expression and ChIP-on-chip studies. The latter is a powerful method for determination of transcription factor binding to the genome, that beautifully complements transcriptomics data. <P>Escherichia coli, the most thoroughly studied model bacterium, is a particularly apposite organism for exploitation of this new technology. It is by far the front runner in comparative genomics, with about 40 whole genome sequences revealing an extraordinary and unexpected genomic diversity and genetic plasticity. And, it remains the organism of choice for the bulk of recombinant protein production in the biotech and biopharmaceuticals industries, where opportunities abound for application of this technology to optimise performance and productivity.<P> We thus propose to enable 'rapid exploitation of the very latest cutting edge technology' (scope of the initiative) by developing next generation microarray methodology to support the academic, public sector and industrial communities in the UK. In so doing we will also generate an exciting and novel data set in comparative genomics of gene expression and transcription factor binding.