Objective
Epilepsy is a prevalent neurological disorder affecting more than 1 % of all people, with the estimated number of 900,000 children and adolescents suffering from active epilepsy in Europe. Most current drugs targeting this disease have important adverse side-effects. An ideal drug would, however, potentiate the endogenous anti-seizure mechanisms that keep most humans epilepsy-free.
To date, these native “anti-seizure mechanisms” have not been identified. Recently, a novel candidate mechanism termed “supply-rate depression” was functionally characterized. It is only induced by excessive synaptic use, after which it dampens all pre-synaptic function for several minutes.
This proposal would test whether lowering the threshold for inducing supply-rate depression is protective against epilepsy using genetically engineered mice, and will additionally test a structure/function hypothesis related to the assembly of the vesicles in presynaptic terminal that could lead to a high-throughput drug screen.
These goals will be accomplished via the following Specific Aims:
1. To generate a synapsin 2 conditional knockout mouse line where synapsin 2 is deleted exclusively at excitatory synapses and thereby speed the onset of the protective mechanism at excitatory synapses.
2. To evaluate the susceptibility to seizures of the synapsin 2 conditional knockout mice using chemically induced models of epilepsy.
3. To apply state-of-the-art electron microscopy tomography techniques to test the structure/function hypothesis that the lengths of presynaptic vesicle tethering units are ~ 40% shorter in presynaptic terminals of synapsin 2 knockout synapses.
Results of this project may justify a large-scale industrial effort for developing a new generation of anti-epileptic drugs that target supply-rate depression. Thus, these new substances should have reduced occurrence and magnitude of unwanted side effects and would immensely improve the well-being of affected people.
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.
- medical and health sciences basic medicine neurology epilepsy
- natural sciences physical sciences optics microscopy electron microscopy
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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.
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.
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.
FP7-PEOPLE-2012-CIG
See other projects for this call
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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
142 20 Praha 4
Czechia
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.