Elucidating the regulation of signal transduction by polyadenylation

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The surprising finding that RNA polyadenylation is upstream of the activation of the PI3K/mTOR pathway suggests that there either is a role for polyadenyation factors in this pathway, or there is an unknown polyadenylated RNA involved in its regulation. Either finding would be fundamentally novel and potentially lead to new anti-inflammatory or anti-cancer drugs. In this project you will use genetic manipulation of cell lines, including siRNA transfection, CRISPR-Cas9 knockout and recombination of genes and overexpression of wild type and mutant proteins to characterise the pathways involved in the regulation of signal transduction by polyadenylation. You will prepare samples for proteomics and RNAseq analysis and use bioinformatics analysis to interpret these genome-wide data. This work will contribute to the development of polyadenylation inhibitors as medicines. Indeed, the polyadenylation inhibitor cordycepin is showing promise in the treatment of breast cancer in mice.