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CAVEHEART SIGNED

Heart regeneration in the Mexican cavefish: The difference between healing and scarring

Total Cost €

EC-Contrib. €

Partnership

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CAVEHEART project word cloud

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

trait surface astyanax permanent inflammatory strategies infarction heart regeneration clodronate loci comprising populations river crispr whereas fish proteins wound liposomes immune immunohistochemistry mutagenesis scarring vitro cave ecm link species mexicanus muscle directed interesting versus population cavefish healing suggesting single utilise differences mammalian zebrafish transcriptomics macrophage mouse prior dwelling remarkably injury repair human fibrotic heal regenerate matrix characterise first quantitative small extracellular cure screen certain influencing phenotype mechanisms hearts therapeutic maximise endogenous close molecule scar form regenerative relative fundamental molecular cardiac directing myocardial genome vivo

Project "CAVEHEART" 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˙499˙429 €
EC max contribution	1˙499˙429 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2016-STG
Funding Scheme	ERC-STG
Starting year	2017
Duration (year-month-day)	from 2017-03-01 to 2022-02-28

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD 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.	UK (OXFORD)	coordinator	1˙499˙429.00

Map

Project objective

Whereas the human heart cannot regenerate cardiac muscle after myocardial infarction, certain fish efficiently repair their hearts. Astyanax mexicanus, a close relative of the zebrafish, is a single fish species comprising cave-dwelling and surface river populations. Remarkably, while surface fish regenerate their heart after injury, cavefish cannot and form a permanent fibrotic scar, similar to the human heart. Using transcriptomics analysis and immunohistochemistry, we have identified key differences in the scarring and inflammatory response between the surface and cavefish heart after injury. These differences include extracellular matrix (ECM) proteins, growth factors and macrophage populations present in one, but not the other population, suggesting properties unique to the surface fish scar that promote heart regeneration. The objective of the proposed project is to characterise and utilise these findings to identify therapeutic targets to heal the human heart after myocardial infarction. First, we will analyse the identified differences in scarring and immune response between the fish in detail, before testing the role of the most interesting proteins and macrophage populations during regeneration using CRISPR mutagenesis and clodronate liposomes. Next, we will link the key scarring and inflammatory differences directly to both the genome and the ability for heart regeneration using new and prior Quantitative Trait Loci analyses. This will allow to find the most fundamental molecular mechanisms directing the wound healing process towards regeneration versus scarring. Together with an in vitro and in vivo small molecule screen directed specifically at influencing scarring towards a more ‘fish-like’ regenerative phenotype in the cavefish and mouse heart after injury, this will provide targets for therapeutic strategies to maximise the endogenous regenerative potential of the mammalian heart, with the aim to find a cure for myocardial infarction.

Publications

List of publications.
year	authors and title	journal	last update
2018	William T. Stockdale, Madeleine E. Lemieux, Abigail C. Killen, Juanjuan Zhao, Zhilian Hu, Joey Riepsaame, NoÃ©mie Hamilton, Tetsuhiro Kudoh, Paul R. Riley, Ronny van Aerle, Yoshiyuki Yamamoto, Mathilda T.M. Mommersteeg Heart Regeneration in the Mexican Cavefish published pages: 1997-2007.e7, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.10.072	Cell Reports 25/8	2019-11-08
2018	Jocelyn L.Y. Tang, Yu Guo, William T. Stockdale, Kerisha Rana, Abigail C. Killen, Mathilda T.M. Mommersteeg, Yoshiyuki Yamamoto The developmental origin of heart size and shape differences in Astyanax mexicanus populations published pages: 272-284, ISSN: 0012-1606, DOI: 10.1016/j.ydbio.2018.06.009	Developmental Biology 441/2	2019-06-13

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