Dr Cameron Osborne
Dr Cameron Osborne’s Group
Genome Organisation and Regulation Group
Department of Medical and Molecular Genetics
School of Basic & Medical Biosciences
The Role of Genome Organization in Health and Disease
Genome organization has profound influence on cellular function, ranging from contact with specialised nuclear sub-compartments, to intimate contact between linearly separated regulatory elements. A growing body of evidence indicates disruption of genome organisation can have drastic consequences. We study how these layers of genomic organization contribute to normal cellular function and how they are perturbed in disease.
Our previous investigations have included the organization of transcription at hubs called transcription factories, where widely separated, transcribing genes cluster (Osborne et al., Nature Genetics, 2004). Our evidence indicates gene co-association at factories does not occur randomly, but instead displays preferred interactions of certain genes (Osborne et al., PLoS Biology, 2007). Moreover, we identified preferred interactions of recurrent chromosomal translocation partner genes at transcription factories, which raises the prospect that these sites may provide a location where cancer-causing rearrangements occur (Osborne et al., PLoS Biology, 2007; Osborne, Clinical Cancer Research, 2014).
Recently our research has centred on the long-range interactions of promoters that regulate transcription (Mifsud et al., Nature Genetics, 2015). We enriched Hi-C genome interaction libraries for interactions of nearly 22,000 promoters. We uncovered extensive networks of conserved and cell-type specific interactions of active and inactive genes to elements marked by regulatory epigenetic signatures. Our data connected many GWAS SNPs to candidate gene targets that would otherwise be challenging to link.
Integrated with other NGS datasets, this new technology provides a means to uncover regulatory elements that control transcription. A complete account of regulatory influences is essential to fully realise how genes are controlled. Moreover, these studies can provide insight into the mechanisms of transcriptional dysregulation that underlie disease. In our current research, we aim to uncover the changes to regulatory interactions that are associated with altered gene expression patterns in leukaemia, and provide new insight into the structural mechanics of transcriptional control.