MicroRNA regulation in the inflammatory response

MicroRNAs (miRNAs) are essential regulators of gene expression in most eukaryotes. These small RNA molecules function by binding with imperfect complementarity to sites in the 3' untranslated region (UTR) of target mRNAs, leading to a reduction in synthesis of the corresponding protein. The Jopling lab has extensive experience in understanding the mechanisms driving miRNA regulation.
This project aims to understand miRNA regulation in the context of the inflammatory response, in which cells rapidly switch on the production of many mRNAs that encode inflammatory proteins. We hypothesise that an increase in poly(A) tail length in the inflammatory response, previously identified by the de Moor lab, affects miRNA binding and regulation of inflammatory mRNAs. We also hypothesise that newly synthesised mRNAs are differently regulated by miRNAs compared to the stable pool of existing mRNAs.
This PhD project aims to investigate these hypotheses using cultured RAW246.7 macrophages stimulated with lipopolysaccharide to induce an inflammatory response. The results of this project will considerably enhance our understanding of how miRNA regulation occurs in the cell. It will also provide important insight into the regulatory events that occur in the inflammatory response, the correct regulation of which is vital to the maintenance of a healthy organism.