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Elucidating the involvement of neutrophils in the pathogenesis of tuberculosis using a zebrafish model

Objective

Tuberculosis has afflicted humans for about 70,000 years and continues to take a huge toll on human health. The increase of drug-resistant Mycobacterium tuberculosis and the limited effectiveness of the existing treatments make urgent a deeper understanding of its immunopathogenesis. The role of macrophages in the disease has been intensively studied, but little is known about the involvement of neutrophils. Recent findings indicate that neutrophils play crucial roles in the pathogenesis of tuberculosis that are unknown until the present. Thus, in this project I will use the recognized zebrafish-Mycobacterium marinum infection model, available in the host lab, to study the role played by neutrophils in mycobacterial infection. I propose to use this infection model combined with in vivo imaging of the interactions host-pathogen, gain and loss of gene function strategies, the use of zebrafish transgenic and mutant lines, gene expression analysis, and multitude of other techniques available in the host lab to study (1) how mycobacteria can evade neutrophil recruitment and phagocytosis, (2) what is the origin of the two functionally different neutrophil populations observed in mycobacterial infection, (3) how neutrophils can kill mycobacteria in the absence of macrophages and without any physical interaction, and (4) why neutrophils act as macrophage scavengers. The elucidation of all these questions never studied before will allow me to shed light on the involvement of neutrophils in the pathogenesis of tuberculosis, and will represent a relevant improvement in the field with biomedical implications. Moreover, it will be a crucial step in my scientific career thinking of becoming a group leader in the field of immunology and infectious diseases, since I will have the opportunity to work in a relevant biomedical question, with the support of the main experts in the field, in an unsurpassable scientific environment, and with the best facilities.

Fields of science (EuroSciVoc)

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Programme(s)

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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.

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.

MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2015

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Coordinator

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 183 454,80
Address
TRINITY LANE THE OLD SCHOOLS
CB2 1TN CAMBRIDGE
United Kingdom

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Region
East of England East Anglia Cambridgeshire CC
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 183 454,80
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