Our highly collaborative research programme utilises a broad range of approaches – from computational and functional genomics to focused molecular, biochemical, and cell biological methods – to study fundamental questions relevant to RNA biology. We have pioneered the development and application of technologies for the genome-wide quantitative profiling of transcriptomes, RNA interactomes, as well as new CRISPR-based methods designed to elucidate RNA regulatory networks. These efforts are uncovering remarkable landscapes of regulation that await further investigation. Much of our current research is focused on understanding the functions of a highly conserved programme of switch-like alternative splicing events comprising 3-27 nucleotide-long neuronal ‘microexons’. These tiny exons are important for the regulation of protein interactions with critical roles in the differentiation and function of neurons, and in higher-order cognitive functioning. We have further observed evidence that microexon disruption represents a convergent mechanism linked to autism spectrum disorder, raising exciting possibilities for the development of new therapeutic strategies. A particular focus of our collaborative research at King’s is the development of RNA sensor-based therapeutic strategies that are capable of selectively rescuing functional homeostasis to pathogenically-altered neurons in the context of brain disorders, including autism
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