Objective
Metabolism generates vast quantities of acid, which exerts broad-spectrum biological effects because protein protonation is a powerful post-translational modification. Regulation of intracellular pH (pHi) is therefore a homeostatic priority, but carefully orchestrated proton dynamics are a versatile signal.
Extracellular acidity is an established chemical signature of tumours and has recently been proposed to convey a signal that shapes the phenotypic landscape of cancer. Cancers genetic instability yields diversity in acid handling and signalling, forming a substrate for selection under acid-stress. This is a plausible mechanism for disease progression and an analogy can be drawn to experimentally-verified hypoxic selection.
Current models of acid handling in cancer are, however, based on population-averages of observations made at the cell level. This fails to appreciate diversity and the complexity inherent in tissues. We will produce a more complete understanding of acid handling that accounts for diffusive transport across tissue compartments and the role of the tumour stroma. A systems-approach of characterising pH-regulatory processes cell-by-cell will identify which components are liable to vary, and thus are a substrate for acid-driven somatic evolution.
The long-term effects of proton signals on gene expression have not been tested, despite evidence for proton-sensing transcription factors. To address the mechanism for adaptation to acid-stress, proton-sensing transcription factors will be characterised from studies of gene expression under chemically and optogenetically operated pH stimuli.
The definition of a cells fitness to survive at a particular microenvironment pH and its relationship with stemness remain unclear. Phenotyping pHi-gated subpopulations in terms of growth, stemness and tumourigenicity will define pH-fitness and its role in aggressiveness. In evolving to survive metabolism, cancer cells may acquire the ability to thrive in new niches.
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 biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
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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)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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.
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.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2016-COG
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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.
OX1 2JD Oxford
United Kingdom
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.