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Exploring the mechanisms of long-term tumour evolution and genomic instability in marine transmissible cancers

Project description

Cancer evolution through the lens of transmissible cancers

Transmissible cancers are cancers that can spread through populations by the transfer of living cancer cells between animals. While only three such cancers are known in terrestrial animals, marine bivalves (including clams, mussels and cockles) are affected by at least 10 separate transmissible cancers, which are spread via waterborne transfer of cancer cells. The ERC-funded CellFish project aims to investigate the origins and evolution of marine transmissible cancers through a large-scale comparative genomic study, leveraging extensive tumour sampling across continents and technologies such as laser microdissection and high-performance computing. As some transmissible cancers can survive for thousands of years, they provide a unique opportunity to study cancer biology and evolution, as well as the mechanisms and consequences of genomic instability.

Objective

Cancers are proliferative outgrowths of abnormal cells driven by a selfish evolutionary programme. Most cancers arise from and remain within the bodies of their respective host individuals. Rarely, however, cancers may escape their hosts to become ‘transmissible cancers’, infectious cell lineages that spread between individuals by direct transfer of cancer cells. As parasitic cancers capable of surviving for millennia, transmissible cancers offer a unique model for exploring how mutation, selection and cellular processes mould and constrain selfish tumour evolution.

Marine bivalves (shellfish including clams, mussels and cockles) are affected by at least 10 transmissible cancers, which spread via waterborne cell transfer. The recurrent emergence of long-lived cancers in shellfish provides a valuable resource for comparative studies aiming to probe the basic mechanisms of tumour evolution, including extreme genomic instability. Yet, the evolutionary histories of these cancers are poorly understood.

My vision is to elucidate the origins and evolution of marine transmissible cancers by conducting a large-scale comparative genomic study of these cancers. My aims are to:

1. Understand how transmissible cancers arise, mutate and spread under the sea

2. Identify the mechanisms and consequences of genomic instability in transmissible cancers.

My research approach will involve:

- Extensive tumour sampling across continents

- Generation of high-quality bivalve genome assemblies

- Application of state-of-the-art technologies, including laser microdissection and single-cell sequencing, to hundreds of tumours

- Development of specialised methods for comparative cancer genome analysis.

The intrinsic heterogeneity and short lifespans of most cancers may obscure their underlying biological patterns. By examining the convergent evolution of 10 long-lived cancers through a comparative-genomics lens, I intend to deliver fundamental insights into cancer biology and evolution.

Fields of science (EuroSciVoc)

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Keywords

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2024-STG

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Host institution

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Net EU contribution

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.

€ 2 497 364,00
Address
TRINITY LANE THE OLD SCHOOLS
CB2 1TN CAMBRIDGE
United Kingdom

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Region
East of England East Anglia Cambridgeshire CC
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 2 497 364,00

Beneficiaries (1)

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