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Molecular and cellular determinants of cell monolayer mechanics

Objective

Epithelial monolayers are amongst the simplest tissues in the body, yet they play fundamental roles in adult organisms where they separate the internal environment from the external environment and in development when the intrinsic forces generated by cells within the monolayer drive tissue morphogenesis. The mechanics of these simple tissues is dictated by the cytoskeletal and adhesive proteins that interface the constituent cells into a tissue-scale mechanical syncitium. Mutations in these proteins lead to diseases with fragilised epithelia. However, a quantitative understanding of how subcellular structures govern monolayer mechanics, how cells sense their mechanical environment and what mechanical forces participate in tissue morphogenesis is lacking.

To overcome these challenges, my lab devised a new technique to study the mechanics of load-bearing monolayers under well-controlled mechanical conditions while allowing imaging at subcellular, cellular and tissue resolutions. Using this instrument, my proposal aims to understand the molecular determinants of monolayer mechanics as well as the cellular behaviours that drive tissue morphogenesis. I will focus on four objectives: 1) discover the molecular determinants of monolayer mechanics, 2) characterise monolayer mechanics, 3) dissect how tension is sensed by monolayers, and 4) investigate the biophysics of individual cell behaviours participating in tissue morphogenesis.

Together these studies will enable us to understand how monolayer mechanics is affected by changes in single cell behaviour, subcellular organisation, and molecular turnover. This multi-scale characterisation of monolayer mechanics will set the stage for new theoretical descriptions of living tissues involving both molecular-scale phenomena (cytoskeletal turnover, contractility, and protein unfolding) operating on short time-scales and rearrangements due to cell-scale phenomena (cell intercalation, cell division) acting on longer times.

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.

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-2014-CoG

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Host institution

UNIVERSITY COLLEGE LONDON
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.

€ 2 000 000,00
Address
GOWER STREET
WC1E 6BT 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.

€ 2 000 000,00

Beneficiaries (1)

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