Project description
Oscillations in an important signalling pathway may encode orders for stem cells in the skin
You may never have wondered what a swinging pendulum, a vibrating guitar string, and the extracellular-signal-regulated kinase (ERK) signalling pathway in epidermal stem cells might have in common. Scientists have the answer and it resides in the oscillatory nature of all these things. ERK dynamics have been shown to encode information in some epithelial cell lines and ERK signalling has been shown to modulate epidermal stem cell state (maintenance, commitment or terminal differentiation). The PulsatERK project is going to find out whether these two are related. Fourier analysis will enable characterisation of the ERK oscillations. They will then be artificially applied to stem cells in an effort to recreate the specific states with important applications to wound healing.
Objective
Understanding how stem cells maintain homeostasis in the epidermis is of great interest to regenerative medicine. Previous studies have identified the crucial role ERK signalling plays in coordinating homeostasis. Intriguingly, and somewhat paradoxically, ERK signalling has been shown to regulate divergent epidermal stem cell outputs; from maintenance, to commitment, and terminal differentiation. Uncovering how the activity of a single signalling pathway can regulate such divergent responses can not only allow us to robustly control epidermal stem cell behaviour but will also have far reaching implications for both the fields of stem cell and cancer biology. Importantly, ERK signalling manifests in a dynamic/pulsatile manner, and these dynamics have been shown to encode information in other epithelial cell lines. If ERK dynamics can encode information that regulates the divergent outputs of epidermal stem cells remains to be explored. My goal is to employ an interdisciplinary approach that combines electrical, and biomedical engineering approaches with those of stem cell biology to decipher the information encoded in the dynamics of ERK signalling that control epidermal stem cell outputs. To achieve this, I will first identify ERK activity signatures associated with the different cell states of the epidermis (stem, committed, and differentiated) using live primary human epidermal cells expressing a Förster Resonance Energy Transfer based ERK reporter. I will then decode these signatures using quantitative Fourier analysis to identify the key amplitude and frequency parameters associated with each epidermal cell state. Further, these parameters will then be tested for their ability to maintain the associated states under experimental conditions that enable control of ERK dynamics. The precise regulation afforded by these experimental conditions will also be harnessed to achieve dedifferentiation of committed cells into a stem cell state.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences mathematics pure mathematics mathematical analysis fourier analysis
- natural sciences biological sciences cell biology
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine physiology homeostasis
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
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 - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2018
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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.
WC2R 2LS London
United Kingdom
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