Project title: Understanding Alternative Splicing in Human Cancerby Proteomics Informed by Transcriptomics (PIT)
Summary: Large-scale consortia-led “omics” studies from several hundred patients have facilitated a better understanding of pan-cancer genomes, transcriptomes, and proteomes. However, studies integrating pan-cancer “omics” datasets have been lacking, which has limited how, for example, misregulation of transcriptomes impacts on proteomic diversity in human cancer. Alternative pre-mRNA splicing (AS) is a ubiquitous genetic process that results in the “shuffling” of coding and non-coding information in the genome, to result in proteomic diversity. Recently, misregulation of AS has been associated with cancer phenotypes, but little is known of the global impact on pan-cancer proteomes. This project will utilise novel pipelines of proteomics informed by transcriptomics (PIT) to study qualitative and quantitative changes in human pan-cancer proteomes. Our interdisciplinary approach will facilitate a greater understanding of how misregulation of AS in cancer impacts on proteomic diversity. Our findings are likely to yield potential cancer biomarkers and possible therapeutic targets, and will provide the student with valuable multidisciplinary training of clinical relevance.