The evolution of riboregulation in mycobacterial pathogens and its role in host-pathogen interactions (360G-Wellcome-099817_Z_12_Z)

In the past decade, non-coding RNAs (ncRNAs), including antisense RNAs (asRNAs), small intergenic RNAs (sRNAs), and elements within the untranslated regions (UTRs) of genes, have emerged as widespread and important regulators of bacterial gene expression. The genus Mycobacterium contains a number of clinically relevant lineages, including the slow-growing members of the M. tuberculosis complex (MTBC), such as M. tuberculosis and M. bovis; facultativepathogens such as M. marinum; and the rapidly growing, multidrug resistant, opportunistic pathogen M. abscessus. Although ncRNAs are known to exist in a number of mycobacteria, their roles are still largely unclear. Using comparative transcriptomic analyses and host cell infection models, thisproject seeks to further understand the prevalence, distribution and functionsof ncRNAs in mycobacteria. Key goals are: " To compare the ncRNA transcriptional patterns of an obligate intracellular pathogen (M. bovis) with those of a closely related facultative pathogen (M. marinum) using computational methods. " To understand the roles of sRNAs in the infection process via RNA-seq analysis of M. abscessus during infection of THP-1 cells. " To uncover the targets of selected sRNAs via experimental approaches. " To offer an insight into the mechanistic aspects of target recognition by searching for sRNA chaperone proteins.