Descripción del proyecto
Un cribado hologenómico para identificar nuevas dianas terapéuticas contra la tuberculosis
La tuberculosis es un problema de salud mundial agravado por la aparición de patógenos farmacorresistentes. Por ello, es necesario comprender la interacción hospedador-patógeno para desarrollar nuevas terapias dirigidas al hospedador que aumenten la capacidad del sistema inmunitario para combatir la bacteria «Mycobacterium tuberculosis» (Mtb). El equipo del proyecto Host-TB, financiado con fondos europeos, empleará la tecnología de edición CRISPR para realizar un cribado hologenómico en macrófagos humanos infectados por Mtb. El objetivo principal es identificar genes que participan en la interacción con el patógeno, así como caracterizar de manera exhaustiva las rutas asociadas. Los resultados del proyecto podrían favorecer la identificación de nuevas dianas terapéuticas contra la tuberculosis.
Objetivo
With more than 10 million cases annually, tuberculosis (TB) remains a global health problem. TB epidemic is exacerbated by the spread of multidrug-resistant TB. Host-directed therapies (HDTs) can improve immune mechanisms by augmenting the ability of host cells to kill M. tuberculosis (Mtb) or by modulating the immune response to prevent excessive inflammation, cell death and tissue damage. Progress with HDT development has been slowed down by the limited understanding of host-pathogen interactions during Mtb infection. Screens of the whole human genome can identify novel genes involved in the immune responses to Mtb infection and susceptibility to TB. Previously, we successfully used genome-wide association studies to identify human genes associated with susceptibility to TB. Here, we will for the first time use the groundbreaking CRISPR technology to screen the human genome in macrophages infected with Mtb and discover genes that are critically involved in host-pathogen interactions. Then, we will comprehensively characterise pathways that mediate impacts of these genes on both the human macrophage and the intracellular Mtb bacilli using dual transcriptome analyses and high-throughput microscopy assays. This novel approach will dissect crucial mechanisms of host-pathogen interaction during Mtb infection and will point to new targets for HDTs of TB.
Ámbito científico
Palabras clave
Programa(s)
Régimen de financiación
ERC-ADG - Advanced GrantInstitución de acogida
CB2 1TN Cambridge
Reino Unido