000404116 001__ 404116
000404116 005__ 20230212180927.0
000404116 0247_ $$2CORDIS$$aG:(EU-Grant)772022$$d772022
000404116 0247_ $$2CORDIS$$aG:(EU-Call)ERC-2017-COG$$dERC-2017-COG
000404116 0247_ $$2originalID$$acorda__h2020::772022
000404116 035__ $$aG:(EU-Grant)772022
000404116 150__ $$aSpatiotemporal regulation of localization and replication of M. tuberculosis in human
macrophages$$y2018-09-01 - 2024-02-29
000404116 371__ $$aThe Francis Crick Institute$$bThe Francis Crick Institute$$dUnited Kingdom$$ehttp://www.crick.ac.uk/$$vCORDIS
000404116 372__ $$aERC-2017-COG$$s2018-09-01$$t2024-02-29
000404116 450__ $$aDynaMO_TB$$wd$$y2018-09-01 - 2024-02-29
000404116 5101_ $$0I:(DE-588b)5098525-5$$2CORDIS$$aEuropean Union
000404116 680__ $$aMycobacterium tuberculosis (Mtb) is a very successful intracellular pathogen: in 2014, tuberculosis (TB) caused 1.5 million human deaths (World Health Organisation). To cause disease and disseminate to other hosts, Mtb needs to replicate within human cells. In spite of its enormous relevance for TB pathogenesis, the precise sites of Mtb replication in host cells remain unknown. This surprising gap in knowledge is in part due to the lack of appropriate imaging technologies that have precluded comprehensive understanding of the fundamental biology that underpins Mtb-host cell interactions critical to design rational interventions. Here, we propose to use a series of cutting-edge imaging approaches in human macrophages to: (1) define how the dynamic interactions between Mtb populations and organelles impact Mtb replication; (2) identify critical host and bacterial components that regulate Mtb replication and (3) characterise the host cell death pathways that control Mtb replication. For this, we will benefit from technologies developed in our group to image and quantify Mtb localisation and replication, such as live cell imaging, super resolution (SR) microscopy and correlative live cell 3D- electron microscopy (CLEM). We will refine these approaches to challenge the current limits of cell-based, high content imaging by combining human stem cell-derived macrophages with adhesive micropattern technologies for single cell analysis; this allows us to identify where and when Mtb replicate and how the interplay between host cells and Mtb impacts this process. Together, this proposal can uncover novel cellular pathways defining the intracellular sites that allow or restrict Mtb replication in human macrophages, thereby advancing the fields of both cell and infection biology. The characterization of the site of intracellular replication of Mtb can open avenues for a deeper understanding of human TB pathogenesis and facilitate development of vaccines and antibioo be here soon
000404116 909CO $$ooai:juser.fz-juelich.de:846618$$pauthority$$pauthority:GRANT
000404116 909CO $$ooai:juser.fz-juelich.de:846618
000404116 970__ $$aoai:dnet:corda__h2020::f3bb26fbf68b3b41794707568038040a
000404116 980__ $$aG
000404116 980__ $$aCORDIS
000404116 980__ $$aAUTHORITY