Objective
A remarkable feature of the brain is its ability to adapt to changing environmental conditions. Modulation of synaptic strength and neuronal circuitry underlies experience-dependent learning, and requires widespread changes in gene expression. Following neuronal depolarisation, intracellular signalling results in rapid induction of many activity-regulated genes (ARGs). There are numerous interconnected levels of gene regulation; one critical aspect relates to the three-dimensional conformation of chromosomes within the nucleus. Looping of genes to regulatory regions and to other genes is required for transcriptional activation in other cell types, but remains largely unexplored in neurons. In this proposal, I will investigate how the genome architecture changes during neuronal depolarisation, and how this influences activity-induced transcription and neuronal plasticity. I will first map the genomic interactions of ARGs in neurons before and after depolarisation. This experimental approach will allow identification of enhancer-promoter loops and multi-gene complexes in an unbiased manner. Single-cell imaging studies will be performed to quantify the frequency of interactions across individual neurons. I will use super-resolution microscopy to simultaneously analyse multiple loci with high precision, providing unprecedented detail of gene interactions in response to neuronal activity. Finally, I will use genome editing to disrupt specific chromosomal contacts and evaluate the transcriptional induction of associated genes. I will assess whether loss of genomic contacts affects dendritic growth, a process associated with neuronal plasticity and dependent on ARG induction, to understand the biological implications of chromosome looping. The aim of this project is to discover novel molecular mechanisms that govern transcription during neuronal activation, which is critical in experience-dependent learning.
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 cell biology cell signaling
- medical and health sciences medical biotechnology genetic engineering gene therapy
- natural sciences physical sciences optics microscopy super resolution microscopy
- natural sciences biological sciences genetics chromosomes
- natural sciences biological sciences genetics genomes
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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-RI - RI – Reintegration panel
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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-2015
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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.