Genes within cells are copied into a pre-messenger RNA (pre-mRNA) which is used as a template for protein production. All information contained within genes is not required for making proteins. Unwanted information, therefore, must be removed from the pre-mRNA before it is used for protein production. Unwanted information is removed, or "spliced", from pre-mRNA by a process similar to the editing of unwanted frames from a film. One end of the region to be removed is first cut then the other end is cut while the two remaining pieces are "spliced" together. This "splicing" of the pre-mRNA is very important because it must occur accurately in order for functional proteins to be produced. The regulation of splicing is essential for all aspects of human biology. Splicing is required for proper embryo development and differentiation of all tissues and organs as well as being vital for organisms to respond to their environment and adapt to stresses or nutrient deprivation. Defects in pre-mRNA splicing are associated with a wide range of diseases including diabetes, cancer, deveopmental disorders and age related diseases. Research in the lab utilises biochemical, molecular biology and genetic approaches to understand how pre-mRNA splicing is carried out and regulated within cells with an emphasis on how disease associated genetic variants disrupt splicing.

The lab also has interests in the functional analysis of non-coding RNAs (ncRNAs). Eukaryotic genomes are pervasively transcribed, producing numerous ncRNAs. Some ncRNAs have been extensively analysed and appear to participate in essential cellular functions. ncRNAs have also been found associated with disease states. However, the majority of ncRNAs have not been ascribed to any specific function, mainly due to the lack of molecular resources. To facilitate large-scale functional analyses of ncRNAs and to systematically determine their roles in essential cellular processes, we have constructed the first collection of molecular barcoded ncRNA deletion strains in the model organism Saccharomyces cerevisiae. We are using this deletion collection resource and other new tools in yeast for the functional analysis and detection of higher order interactions between different ncRNAs.

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