microRNAs (miRNAs) are a family of small RNAs that play important roles in the regulation of target genes by interacting/binding with specific sites in 3'untranslated regions of messenger transcripts to repress their translation or regulate degradation. Silencing of miRNAs in vivo with antagomiRs is a new and expanding area of technology that is considered a powerful approach that may represent a new therapeutic strategy for targeting cardiac disease. Using microarray analysis, we have identified a number of miRNAs that are differentially regulated in mice with increased or decreased PI3K activity (a critical gene in the athlete's heart). This project will examine whether inhibition of miRs (i.e. mimicking what happens in a setting of physiological hypertrophy) using an antagomiR can improve cardiac function in vivo.
Another area that this particular project can explore is the characterisation of novel genes to treat heart failure. By microarray we have identified a cohort of genes that may be important for the physiological hypertrophic response induced by the PI3K pathway. Avenues that can be undertaken include performing bioinformatics analysis of novel genes to elucidate gene/protein structure and function, characterisation of gene expression in the heart after pathological and physiological stimuli, targeting of novel genes in a setting of heart failure to determine if cardiac function has improved.