Micro-RNA regulation of macrophage differentiation and activation (Micros & Macros)

Macrophages are cells of the innate immune system derived from bone marrow progenitor cells differentiated along the myeloid pathway. They are phagocytic cells with roles in wound healing, tissue homeostasis and in the first line of defence against invading pathogens. MicroRNAs are short, non-coding sequences of RNA (18-22 nt) that act as post-transcriptional regulators. They target complementary sequence in the 3'UTR of messenger-RNA. Binding to the mRNA inhibits translation and/or leads to the degradation of the target mRNA. MicroRNA expression is dynamic and they appear to carry out many different roles. Developmentally they are involved in many processes including, haematopoiesis, muscle myotube formation and neural development. Macrophage activation occurs upon interaction with a pathogen and this initiates many pathways that tailor a response directed at pathogen destruction. Macrophage activation must be carefully regulated as mis-regulation can cause inflammatory diseases which may prove fatal for the host. Recently microRNAs (miRs) have been implicated in the differentiation and activation of macrophages. miR-424 has been shown to be involved in monocyte/macrophage differentiation, while miR-155 and miR-146 are up-regulated after macrophage activation with lipopolysaccharide. This project will use SOLEXA sequencing to identify miRNAs with differential expression during the differentiation of macrophages from bone marrow progenitor cells and their subsequent activation. Further studies will then determine the role played by selected miRNA in macrophage differentiation/activation and identify genes targeted by regulatory miRNA during these processes.