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COLGENES SIGNED

Defining novel mechanisms critical for colorectal tumourigenesis

Total Cost €

EC-Contrib. €

Partnership

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COLGENES project word cloud

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

applicability organoid cultures separate sequencing crispr shift frequently hypothesize led stages function genetic broadly begin therapeutic segregate model tumour tumourigenesis potentially foundation mediators clear alterations implications mouse mutational colorectal full screen mutated genes mutations crucially functionally causative groups frequency difficult paradigm therapeutics entire combination driving tumourigenic models relevance unclear therapies larger cancer disruption efforts concerted subset earliest genome avenues human think driver noise performed small initiation spectrum crc validate mechanisms oncogenesis thousands 3d infrequently profound

Project "COLGENES" data sheet

The following table provides information about the project.

Coordinator	THE UNIVERSITY OF EDINBURGH Organization address address: OLD COLLEGE, SOUTH BRIDGE city: EDINBURGH postcode: EH8 9YL website: www.ed.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˙498˙618 €
EC max contribution	1˙498˙618 € (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 2017-08-01 to 2022-07-31

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	THE UNIVERSITY OF EDINBURGH THE UNIVERSITY OF EDINBURGH Organization address address: OLD COLLEGE, SOUTH BRIDGE city: EDINBURGH postcode: EH8 9YL website: www.ed.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 (EDINBURGH)	coordinator	1˙498˙618.00

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Project objective

Cancer genome sequencing has led to a paradigm shift in our understanding of oncogenesis. It has identified thousands of genetic alterations that segregate into two groups, a small number of frequently mutated genes and a much larger number of infrequently mutated genes. The causative role of frequently mutated genes is often clear and are the focus of concerted therapeutic development efforts. The role of those infrequently mutated is often unclear and can be difficult to separate from ‘mutational noise’. Determining the relevance of low frequency mutations is important for providing a full understanding of processes driving tumourigenesis and if functionally relevant may have broader implications on the applicability of targeted therapies.

This project aims to begin addressing this by defining the function of all genes mutated in colorectal cancer (CRC) in the earliest stages of tumour formation. I have performed a whole genome screen in a 3D organoid CRC initiation model identifying several potentially important mediators of this process. Crucially, some of these genes are mutated in CRC at low frequency but not described as cancer driver genes. Thus, I hypothesize that rather than ‘mutational noise’ infrequently mutated genes contribute to CRC initiation. I will test this by addressing two aims:

1) Determine the role of genes mutated in CRC during tumour initiation 2) Validate and determine the function of a subset of identified genes potentially defining novel cancer mechanisms

I will use a combination of CRISPR genetic disruption in state-of-the-art 3D mouse and human organoid cultures and advanced mouse models to address these aims. This comprehensive approach will provide a foundation for understanding the importance of the entire spectrum of mutations in CRC and open new avenues of research into the function of these genes. More broadly, it has the potential to make a profound impact on how we think about tumourigenic mechanisms and cancer therapeutics.

Publications

List of publications.
year	authors and title	journal	last update
2017	Kevin Myant COLGENES - Defining novel mechanisms critical for colorectal tumourigenesis published pages: 12-14, ISSN: 2398-7073, DOI: 10.21820/23987073.2017.10.12	Impact 2017/10	2020-01-27

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