Objective
An expanded GGGGCC repeat in a non-coding region of the C9orf72 gene is the most common known cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The repeat RNA is transcribed and accumulates in neuronal RNA aggregates, implicating RNA toxicity as a key pathogenic mechanism. However, the pathways that lead to neurodegeneration are unknown. My lab has made pioneering contributions to the understanding of C9orf72 FTD/ALS, and reported the first structure of the repeat RNA, and the first description of both sense and antisense RNA aggregates in patient brain. We have now developed new disease models that allow, for the first time, the dissection of RNA toxicity both in vivo and in sophisticated neuronal culture models. We have also used our knowledge of the repeat structure to identify novel small molecules that show very strong binding to the repeats. We will utilise our innovative disease models in a multidisciplinary approach to fully dissect the cellular pathways underlying C9orf72 repeat RNA toxicity in vivo, on a genome-wide scale. Altered RNA metabolism has been implicated in a wide range of neurodegenerative diseases, indicating that our findings will provide profound new insight into fundamental mechanisms of neuronal maintenance and survival. This research programme will also deliver a step change in our understanding of C9orf72 FTD/ALS pathogenesis and provide essential insight for the identification of small molecules with genuine therapeutic potential. RNA-mediated mechanisms are now known to be a common theme in neurodegeneration, suggesting these findings will have broad significance.
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.
- agricultural sciences agriculture, forestry, and fisheries agriculture horticulture fruit growing
- medical and health sciences basic medicine neurology dementia
- medical and health sciences basic medicine physiology
- natural sciences biological sciences genetics RNA
- medical and health sciences basic medicine neurology amyotrophic lateral sclerosis
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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.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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-COG - Consolidator Grant
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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-2014-CoG
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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.
WC1E 6BT 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.