CORDIS
EU research results

CORDIS

English EN
Using CRISPR genome screens and dual transcriptome analyses to dissect host-pathogen interactions in tuberculosis

Using CRISPR genome screens and dual transcriptome analyses to dissect host-pathogen interactions in tuberculosis

Objective

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.
Leaflet | Map data © OpenStreetMap contributors, Credit: EC-GISCO, © EuroGeographics for the administrative boundaries

Host institution

STICHTING VUMC

Address

De Boelelaan 1117
1081 Hv Amsterdam

Netherlands

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 417 662,50

Beneficiaries (2)

Sort alphabetically

Sort by EU Contribution

Expand all

STICHTING VUMC

Netherlands

EU Contribution

€ 1 417 662,50

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE

United Kingdom

EU Contribution

€ 743 263,50

Project information

Grant agreement ID: 832721

Status

Ongoing project

  • Start date

    1 June 2019

  • End date

    31 May 2024

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 2 160 926

  • EU contribution

    € 2 160 926

Hosted by:

STICHTING VUMC

Netherlands