Project description
Worms in the fight against ageing
The synthesis and folding of proteins are paramount to their function. Although organisms have evolved mechanisms for monitoring protein folding in specific organelles within cells, these decline with ageing. As a result, protein aggregates accumulate and cause age-related disorders such as Alzheimer's disease. Using the nematode Caenorhabditis elegans as a model, the EU-funded UCUPA project is investigating the unfolded protein response (UPR) protein quality control mechanism of the endoplasmic reticulum (ER) which declines with ageing. Using genome editing, scientists are evaluating different UPR signalling molecules which will shed light on the mechanisms of ageing. The project will also test novel interventions opening new therapeutic avenues for age-related disorders.
Objective
What defines the functional specialization of a cell is its unique proteome. Proteins need to be translated and properly folded to ensure their biological function. Several protein quality control pathways have arisen during evolution, some of them specialized in monitoring protein folding in specific organelles . As a result of ageing, animals lose their ability to protect their proteome, leading to the accumulation of protein aggregates and the onset of age-related disorders. The Unfolded Protein Response (UPR) of the Endoplasmic Reticulum (ER) is a central protein quality control mechanism that declines with ageing. This project will use the nematode Caenorhabditis elegans as a model to understand age-related proteostasis dysfunction. C. elegans offer many advantages over the use of vertebrate models, such as its short lifespan of about two weeks, reduced costs, and fewer ethical issues. We will focus on the UPR pathway, as changes in this pathway have already been implicated in the ageing process itself and in the onset of age-related disorders, such as Alzheimer’s disease. We propose to use CRISPR genome editing to create C. elegans transgenic reporter strains that enable us to track the activity of different UPR signalling molecules using microscopy and molecular biology techniques. We will monitor two central steps of the IRE-1/XBP-1 UPR pathway (1) the activation of the transmembrane sensor protein IRE-1 and (2) the biogenesis of the transcription factor XBP-1s. After age-related changes have been identified, we will use mutagenesis-based screening assays to screen for novel interventions that prevent UPR pathway shutdown. This research will contribute to a better understanding of why ageing occurs, as well as suggesting new therapeutic avenues for age-related disorders. This proposal will also be instrumental for the development and transference of new skills between the host and the applicant that will lead me towards independence.
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.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences basic medicine neurology dementia alzheimer
- medical and health sciences medical biotechnology genetic engineering gene therapy
- natural sciences biological sciences biochemistry biomolecules proteins protein folding
- natural sciences biological sciences molecular biology
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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.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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) H2020-MSCA-IF-2019
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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.
SN2 1FL SWINDON
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.