Objective
During learning specific neuronal connections are strengthened and weakened to create long-term memory. This requires local regulation of the availability of proteins at the synapse, at a large distance from the cell body, in response to neuronal activity. It is generally recognized that such synaptic plasticity can be achieved through the regulation of translation of localized mRNAs at or near the synapses. Despite the importance of this mechanism in memory and our understanding of neurodegenerative diseases, the molecular basis by which neuronal activation regulates localised translation is still largely unknown in any system.
I propose to address this deficiency by discovering the key regulatory pathway in activity dependent synaptic plasticity in the Drosophila third instar motorneuron synapse, a well established model for generalised synaptic function. My proposal is built on extremely promising unpublished observations showing that a highly conserved mRNA binding protein, Syncrip (Syp) regulates the localized translation of key synaptic mRNAs, such as the conserved scaffolding molecule Discs large, at the motorneuron synapse, in response to neuronal stimulation. Preliminary data from the lab suggests that Syp is post-translationally modified by Calcium/calmodulin-dependent protein kinase II (CaMKII), a well-known kinase that plays essential and conserved roles in memory. I propose to test the hypothesis that binding of Syp to its mRNA targets is regulated by phosphorylation by CamKII. I will test whether Syp is phosphorylated at CamKII consensus sites located in its mRNA binding domains, which have been modelled on the human structure. We will use mass spectrometry to identify these phosphorylation sites and characterise phosphorylation mutants of Syp generated by CRISPR. I also aim to discover the molecular mechanism by which Syncrip regulates the translation of its targets.
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 neurobiology
- natural sciences chemical sciences inorganic chemistry alkaline earth metals
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics RNA
- natural sciences chemical sciences analytical chemistry mass spectrometry
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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-EF-ST - Standard EF
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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-2014
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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.
OX1 2JD Oxford
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.