Objective
The high energy demand of the brain predisposes it to a variety of diseases if energy supplies are interrupted. Neurons are particularly intolerant of inadequate energy supply and die or degenerate in either an acutely or chronically disturbed metabolic environment.
Although neurodegenerative diseases are classically not considered to be caused by disturbed metabolism, bioenergetic defects are emerging as important pathophysiological mechanisms. Several glucose-metabolizing enzymes are involved in regulating cell survival or cell death in neurons and in other cell types, including the mitochondrial glucose-phosphorylating enzyme hexokinase II (HKII). A HKII-centered multiprotein complex, consisting of phosphoprotein enriched in astrocytes (PEA15) and possibly other proteins, has been demonstrated to function as a molecular switch regulating neuronal survival depending on the metabolic state. However, the molecular mechanism by which these protein:protein interactions are regulated remains elusive.
The goal of AINIGMA and of the research proposed here is to unravel the intricate connection of glucose metabolism and the regulation of cell death pathways for neuronal viability or neuronal degeneration. By combining protein interaction studies in live induced pluripotent stem (iPS) cell-derived human neurons using novel biophysical tools such as fluorescence lifetime imaging microscopy (FLIM-FRET) and high throughput live cell RNA interference (RNAi) screens, the regulation of these protein interactions will be investigated. Finally, the impact of these interactions on neuronal survival under metabolic stress as well as the metabolic consequences of these protein interactions will be investigated.
Therefore, AINIGMA will not only provide better insight into physiological and pathophysiological brain function but also form the basis for developing novel treatment approaches for acute and chronic neurodegenerative diseases.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences physical sciences optics microscopy fluorescence lifetime imaging
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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-2013-IOF
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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.
Coordinator
10117 Berlin
Germany
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.