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Septins: from bacterial entrapment to cellular immunity

Objective

The intracellular bacterium Shigella flexneri is an exceptional model pathogen to address key issues in biology, including how bacteria can move inside host cells and escape the immune system. The cytoskeleton has recently emerged to occupy a central role in innate immunity by promoting bacterial sensing and executing antibacterial functions. I discovered that host cells employ septins, a poorly understood component of the cytoskeleton, to restrict the actin-based motility of Shigella and target them for destruction by autophagy, an important mechanism of innate immune defence. However, the processes underlying septin cage assembly, and the breadth of roles for septins in bacterial infection control, remain to be established. I developed zebrafish (Danio rerio) infection models to study the cell biology of Shigella infection in vivo, and to discover new roles for septins in host defence against bacterial infection. This approach has enabled a cutting edge platform for in vivo studies both at the single cell and whole animal level, and provides unprecedented opportunities to follow cytoskeleton dynamics and innate immunity at a resolution that cannot be achieved using any other animal model. I will now exploit the novelty of septin biology, and its direct link to host defence, as the foundation for this research programme. Using Shigella I will: (1) Discover new roles for the cytoskeleton in host defence against bacterial infection, and (2) Investigate the role of septin-mediated host defence mechanisms in vivo using zebrafish models of infection. The results generated from this research programme will provide fundamental advances in understanding septin biology and cellular immunity. They could also suggest the development of new strategies aimed at combating infectious diseases, and possibly other human diseases in which septins have been implicated including neoplasia and neurodegenerative conditions.

Fields of science (EuroSciVoc)

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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)

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.

ERC-COG - Consolidator Grant

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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) ERC-2017-COG

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Host institution

LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE ROYAL CHARTER
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.

€ 2 744 407,00
Address
KEPPEL STREET
WC1E 7HT LONDON
United Kingdom

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Region
London Inner London — West Camden and City of London
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.

€ 2 744 407,00

Beneficiaries (1)

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