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SKINFRET

The involvement of epidermal stem cells in spatiotemporal ERK activity propagation

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
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SKINFRET project word cloud

Explore the words cloud of the SKINFRET project. It provides you a very rough idea of what is the project "SKINFRET" about.

mouse intercellular crossing amplitude artificially timing insights combine marks organotopic matrices microenviromental surrounding living spread lrig1 local reconstruction fret significance mammalian activation maintenance lgr5 named culture possibility recapitulate expertise tissue sensitive signal location observe observation vitro host extracellular shape substrate phd engineered skin human laboratory regulated densities cells spreads epidermis types populations 300 structures concentrically transgenic fibroblast bursts kinase involvement collagen mice light keratinocytes imaging fresh centre stem found pattern strains propagated emergence communicate expressing generating epidermal lgr6 propagation central biosensor localized size visualized suggested effect vivo microenvironment erk

Project "SKINFRET" data sheet

The following table provides information about the project.

Coordinator	KING'S COLLEGE LONDON Organization address address: STRAND city: LONDON postcode: WC2R 2LS website: www.kcl.ac.uk contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	United Kingdom [UK]
Project website	http://www.wattlab.org/
Total cost	195˙454 €
EC max contribution	195˙454 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2015
Funding Scheme	MSCA-IF-EF-ST
Starting year	2016
Duration (year-month-day)	from 2016-06-27 to 2018-06-26

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	KING'S COLLEGE LONDON KING'S COLLEGE LONDON Organization address address: STRAND city: LONDON postcode: WC2R 2LS website: www.kcl.ac.uk contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	UK (LONDON)	coordinator	195˙454.00

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Project objective

Stem cells are central to maintenance of mammalian epidermis. This proposal focuses on how stem cells communicate with their microenvironment by intercellular propagation of growth signal. I will investigate the involvement of epidermal stem cells in a novel growth signal propagation pattern I found in my PhD research. In this research, I visualized extracellular signal regulated kinase (ERK) activity in the skin of living mice by FRET-based observation of transgenic mouse expressing a sensitive biosensor for ERK. By this approach, I found a novel pattern of intercellular ERK activity propagation, which we named SPREAD. In SPREAD, bursts of localized ERK activation concentrically propagated to their surrounding 100 -300 cells. The timing and location of SPREAD emergence suggested the involvement of epidermal stem cells. To test this possibility I will combine my expertise of FRET imaging with in vivo and in vitro systems for mouse and human keratinocytes in the host laboratory. By crossing ERK biosensor mice with various mouse strains that marks Lgr5, Lgr6, or Lrig1 stem cells, I will observe whether the centre cells of SPREADs are epidermal stem cells in vivo. In addition, I will culture keratinocytes expressing the ERK FRET biosensor on an artificially engineered substrate to recapitulate SPREAD in vitro. To study whether SPREADs are also seen in human skin, I will exploit a skin reconstruction system, called organotopic culture. The method allows culture of keratinocytes on collagen matrices embedded with various fibroblast populations with various densities. The significance of the features of SPREAD (shape, size, amplitude etc.) will be addressed by generating various types of ERK activity propagation by using light-induced ERK activation system. This approach will bring fresh insights into how stem cells control their local tissue structures via intercellular propagation of growth signal and how microenviromental factors effect on the propagation pattern.

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