Objective
Non-pathogenic mycobacteria are efficiently phagocytosed by macrophages and killed within phagosomes by acid hydrolases, reactive nitrogen intermediates, and likely other still unidentified factors that are part of the macrophage pro-inflammatory response. In contrast, pathogenic mycobacteria such as M. tuberculosis survive and grow within phagosomes by blocking macrophage pro-inflammatory responses, including the NF-kB transcription system, phago-lysosome fusion, acidification and nitric oxide release. Activation of NF-kB has recently been shown, by the host group, to be essential for macrophages to kill the non-pathogen M. smegmatis.
Here two genomic screening assays are proposed: the first (A) will use RNA micrroarray chips to identify macrophage mRNA¿s t hat are up-regulated in response to M.smegmatis or M.bovis BCG, that behaves like a pathogen. Emphasis will be given to identify macrophage proteins that are potentially involved in killing M.smegmatis; some of these proteins are predicted to be under the control of the NF-kB system. It is also expected that the potential killing proteins may not be up-regulated in BCG-infected cells, that therefore serve as a control.
The second screen (B) involves a recently developed high throughput RNAi approach that will be used to identify proteins that, when knocked down block the ability of GFP-M.smegmatis to fuse with lysosomes labelled with a red marker (rhodamine gold or lysotracker red). These proteins should be positive regulators of phagosome maturation and their identification should facilitate future efforts to understand how the pathogenic mycobacteria block phagosome maturation.
In parallel, RNAi knockdown of putative macrophage killing factors identified in screen A will allow us to test the hypothesis that these proteins indeed facilitate killing of M.smegmatis. The final proof of killing will be sought by testing purified factors for their effects on M.smegmatis growth and survival in vitro.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy
- natural sciences biological sciences genetics RNA
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2005-MOBILITY-7
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
IIF - Marie Curie actions-Incoming International Fellowships
Coordinator
HEIDELBERG
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.