Enhancement: Interactions between the circadian clock and virus infection (360G-Wellcome-083643_Z_07_A)

Daily (circadian) rhythms form a fundamental part of our existence, necessarily so because of our 24h solar environment. We know that the clock consists of an autoregulatory negative feedback loop involving various core clock genes. I seek to understand how the molecular clock affects neural processes to coordinate our rhythmic physiology and behaviour. Until now, addressing this question was not possible. With the recent advent of high-throughput tools to interrogate transcriptional contr ol, global gene expression and the proteome, it is now possible to tackle this problem in a molecular context. Expression of circadian genes starts with binding of transcription factors to DNA, then transcription of those genes into mRNA, and finally translation of this mRNA to protein. Each stage of this process will be interrogated, but in reverse order, starting with DiGE/iTRAQ to assay the proteome, expression microarrays (e.g. Affymetrix/Illumina) to look at transcript levels, and finall y ChIP-chip to address transcription factor binding to promoter regions of circadian genes. The interrelationships between DNA-mRNA-protein dynamics will be modelled using systems biology tools and bioinformatics to identify novel control points. A subset of the novel proteins will be functionally characterised to define novel circadian elements and/or targets for future therapeutic benefit.