Project description
Retroelements and cancer evolution
Nearly 50 % of the human genome consists of mobile genetic elements that are thought to have emerged from the integration of retroelement genomes. Although these are believed to confer novel functions and a host fitness advantage, they may also have an oncogenic role. The EU-funded RETROFIT project aims to detect and quantify the transcription of endogenous retroelements and decipher their participation in the cancer transcriptome. Researchers will identify retroelements that have a potential impact on overall cancer survival rates or that respond to immunotherapy. RETROFIT is expected to unveil novel targets for the design of cancer treatments.
Objective
Exaptation, the co-option of endogenous retroelements (EREs) for new molecular and cellular functions that confer a host fitness advantage, is a major force in evolution, but may also be exploited, through onco-exaptation, by tumour cells to promote the oncogenic process. There are over 4 million well-recognised and annotated individual ERE integrations in the human genome. However, their participation at the level of the more complex transcriptome is far less well understood and, therefore, the number of onco-exaptation events is likely vastly underestimated. To allow detection and quantitation of ERE transcription, we have recently de novo assembled the cancer transcriptome. This resulted in a doubling of the known transcriptome, particularly of unannotated or partially annotated transcripts derived from or overlapping with EREs. Here, we propose to utilise this extended view of ERE transcription as the framework for:
•building a genome-wide map of functionally validated ERE onco-exaptation events and
•pinpointing novel, targetable functions of EREs in immunity, cancer and their intersection
Although we identified thousands of novel ERE-overlapping transcripts in cancer, the majority are likely the consequence of transcriptional activation of normally silent EREs, with little or no impact on host cell function. Impactful and inconsequential ERE integrations will be distinguished based on a number of features, including association with cancer overall survival or response to immunotherapy, impact on adjacent gene function, evolutionary conservation and functional domain and folding predictions. Postulated function will ultimately be tested extensively in in vitro cancer cell lines, ex vivo cancer patient material and in vivo mouse cancer models, tailored to the relevant onco-exaptation event. The modification of existing gene function or the creation of new function by ERE onco-exaptation will undoubtedly uncover new targets and opportunities for cancer treatment.
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.
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
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.
-
H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
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-ADG - Advanced Grant
See all projects funded under this funding scheme
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-2020-ADG
See all projects funded under this callHost institution
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.
NW1 1AT London
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.