Identification and functional characterization of chromatin-associated long non-coding RNAs (ca-lncRNAs) involved in innate immune responses
Liraz Shmuel-Galia | Fitzgerald Lab | EMBO Long Term Postdoctoral Award
Long non-coding RNAs (lncRNAs) are important regulators of gene expression in diverse biological contexts. Their role in immune regulation is less understood. Recently, work from the Fitzgerald lab has revealed important functional roles of lncRNAs in innate-immunity. One of these, lincRNA-EPS controls the basal expression of immune genes through regulation of chromatin accessibility. How lincRNA-EPS restrains immune gene expression in macrophages and its in vivo functions remains to be better understood. Combining both the Fitzgerald lab’s expertise in lncRNAs and innate immunity with my own experience in immunity we will unveil lincRNA-EPS mechanism of action and in vivo functions. In addition, we will expand these studies to characterize new lncRNAs that control the inflammatory response.
To this end we will define proteins involved in the lincRNA-EPS complex and study these RNA-protein complexes in vivo.
lncRNAs are often co-expressed with protein-coding genes. However, not all lncRNAs that are co-expressed are functional. To date, function of only a handful of lncRNAs have been described. We hypothesize that functional lncRNAs regulate transcription through their association with chromatin in immune cells similar to lincRNA-EPS. We propose to characterize chromatin-associated lncRNAs in immune cells and identify their genomic targets. The conceptual innovation of this proposal lies in bridging our understanding of gene regulation in innate-immunity and inflammatory response with the expanding field of lncRNAs.
These studies will provide critical insights into the inflammatory response and have the potential for the discovery of new biomarkers or targets for infectious and inflammatory diseases.
