Research SummaryIntermediate Fellowship research summary
The focus of research in my laboratory is the role of RNA-protein and RNA-microRNA interactions in the regulation of mRNA translation, specifically of genes involved in inflammation and cancer. Inflammation is the primary protective response of the body to infection and injury; however unresolved and chronic inflammation is the cause or consequence of major human diseases such as cancer, atherosclerosis, arthritis and Alzheimer’s disease. The mechanism of onset of inflammation is widely studied, however very little is known about the processes that resolve inflammation. It is thought that post-transcriptional regulation of multiple inflammatory genes, involving inhibition of translation or mRNA destabilization, play an important role in inflammation resolution. We are studying the interplay between mRNA-protein and mRNA-miRNA interactions in the regulation of translation of inflammatory genes using both candidate gene and whole transcriptome approaches. We are investigating whether the signal-dependent interactions of specific regulatory proteins with sequence/structural elements in the 3’UTR of mRNAs modulate specific miRNA-mRNA interactions, and vice versa, resulting in fine-tuned control of translation. We are also investigating the role of RNA conformational switches in mediating this crosstalk. Studying these interactions at the whole transcriptome level will provide important insights into the systems biology of inflammation and its resolution.