Team:Paris Bettencourt/Project/TB-ception

Overview

Bacterial vectors offer a biological route to gene and protein delivery to cells such as macrophages. We want to investigate the potential use of E.coli as a bacterial vector to kill M. tuberculosis using two approaches. In the first one we will introduce an expression system containing a gene for a cutinase-like serine esterase that triggers rapid lysis of the mycobacterial cell wall and a gene encoding a protein which forms large pores in the phagosomal membrane where mycobacteria are located, thus releasing the target protein into the cytosol. In the second one we will developed a bacteria-based iRNA delivery system for silencing the coronin-1 gene of the macrophages. Coronin-1 is a protein which surrounds the mycobacterial phagosome allowing mycobacteria to survive within them. Silencing of this gene will result in the enhancement of the lysosome/phagosome fusion.