Project description DEENESFRITPL A genome-wide screen for novel therapeutic targets against tuberculosis Tuberculosis is a global health issue exacerbated by the emergence of drug-resistant pathogens. Understanding the host–pathogen interaction is necessary for the development of novel host-directed therapies that augment the capacity of the immune system to fight Mycobacterium tuberculosis (Mtb). The EU-funded Host-TB project will use the CRISPR editing technology to perform a genome-wide screen on human macrophages infected with Mtb. The key objective is to identify genes implicated in the interaction with the pathogen as well as comprehensively characterise the associated pathways. The project's results have the potential to lead to the identification of novel therapeutic targets against tuberculosis. Show the project objective Hide the project objective 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. Fields of science natural sciencesphysical sciencesopticsmicroscopymedical and health sciencesbasic medicineimmunologymedical and health sciencesclinical medicinepneumologytuberculosisnatural sciencesbiological sciencesgeneticsgenomes Keywords Tuberculosis Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2018-ADG - ERC Advanced Grant Call for proposal ERC-2018-ADG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Coordinator THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Net EU contribution € 1 366 940,49 Address Trinity lane the old schools CB2 1TN Cambridge United Kingdom See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE United Kingdom Net EU contribution € 1 366 940,49 Address Trinity lane the old schools CB2 1TN Cambridge See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 STICHTING VUMC Participation ended Netherlands Net EU contribution € 793 985,51 Address De boelelaan 1117 1081 HV Amsterdam See on map Region West-Nederland Noord-Holland Groot-Amsterdam Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
