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Survive SIGNED

Surviving metabolism: acid handling and signalling

Total Cost €

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EC-Contrib. €

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Partnership

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 Survive project word cloud

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

phi    complexity    vary    tumour    extracellular    proton    convey    sensing    cancer    vast    forming    generates    tumourigenicity    substrate    translational    chemically    protonation    analogy    gene    operated    spectrum    appreciate    stroma    phenotyping    subpopulations    quantities    models    ph    unclear    experimentally    acquire    niches    disease    plausible    liable    compartments    cells    gated    transcription    signal    accounts    verified    averages    aggressiveness    tested    hypoxic    stimuli    fails    tissues    dynamics    complete    fitness    transport    microenvironment    biological    intracellular    signalling    post    acid    characterised    orchestrated    genetic    thrive    drawn    handling    components    acidity    tissue    inherent    progression    evolution    phenotypic    stemness    characterising    stress    made    signals    population    expression    relationship    modification    carefully    cell    definition    optogenetically    regulation    yields    diffusive    signature    mechanism    somatic    chemical    shapes    broad    protein    regulatory    observations    homeostatic    versatile    landscape    exerts    survive    powerful    tumours    diversity    metabolism    instability    despite   

Project "Survive" data sheet

The following table provides information about the project.

Coordinator
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD 

Organization address
address: WELLINGTON SQUARE UNIVERSITY OFFICES
city: OXFORD
postcode: OX1 2JD
website: www.ox.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]
 Total cost 1˙922˙575 €
 EC max contribution 1˙922˙575 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-06-01   to  2022-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD UK (OXFORD) coordinator 1˙922˙575.00

Map

 Project 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. Cancer’s 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 cell’s 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.

 Deliverables

List of deliverables.
Open Research Data Open Research Data Pilot 2019-05-30 15:20:37

Take a look to the deliverables list in detail:  detailed list of Survive deliverables.

 Publications

year authors and title journal last update
List of publications.
2019 Pawel Swietach, Stefania Monterisi
A Barter Economy in Tumors: Exchanging Metabolites through Gap Junctions
published pages: 117, ISSN: 2072-6694, DOI: 10.3390/cancers11010117
Cancers 11/1 2020-01-29
2019 Johanna Michl, Kyung Chan Park, Pawel Swietach
Evidence-based guidelines for controlling pH in mammalian live-cell culture systems
published pages: , ISSN: 2399-3642, DOI: 10.1038/s42003-019-0393-7
Communications Biology 2/1 2020-01-29
2019 Pawel Swietach
What is pH regulation, and why do cancer cells need it?
published pages: 5-15, ISSN: 0167-7659, DOI: 10.1007/s10555-018-09778-x
Cancer and Metastasis Reviews 38/1-2 2020-01-29
2018 Shen-Han Lee, Dominick McIntyre, Davina Honess, Alzbeta Hulikova, Jesús Pacheco-Torres, Sebastián Cerdán, Pawel Swietach, Adrian L. Harris, John R. Griffiths
Carbonic anhydrase IX is a pH-stat that sets an acidic tumour extracellular pH in vivo
published pages: 622-630, ISSN: 0007-0920, DOI: 10.1038/s41416-018-0216-5
British Journal of Cancer 119/5 2020-01-29

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The information about "SURVIVE" are provided by the European Opendata Portal: CORDIS opendata.

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