Project description
Microglial proteins and Alzheimer's disease
As the global population ages, diseases associated with ageing increase in prevalence. Among them is the incurable Alzheimer's disease (AD), a debilitating neurodegenerative condition causing loss of memory and cognition. Recently, researchers identified a protective mutation in a gene associated with AD. The gene codes a protein abundant in microglia, cells that engulf and digest cellular debris and dead cells in the brain and spinal cord, playing an important role in immunity. iMIND is creating human microglial cell lines from both healthy and AD-derived stem cells. These will be edited to express the mutation. Studies may elucidate novel molecular mechanisms of AD and point to therapies.
Objective
Alzheimer’s disease (AD) is an irreversible neurodegenerative condition affecting 50 million people worldwide. To date, no disease modifying therapy for AD is available. Neuroinflammation is emerging as an important component of the disease. A recent GWAS analysis identified a rare protective coding mutation (P522A) in the PLCG2 (Phospholipase C Gamma 2) gene that is associated with AD. Interestingly, the gene encodes a transmembrane signaling enzyme that is highly enriched in microglia. The major aim of the proposal revolves around the functional characterization of the P522A mutation in microglia. To that aim, using an array of biochemical, imaging, functional, and transcriptomic assays, we will investigate human microglia generated from control- and AD patient-derived induced pluripotent stem cells (iPSCs). iPSCs will be gene-edited to generate P522A mutated isogenic cell lines. The proposal aims at identifying novel therapeutic targets and, in line with the objectives of the H2020 Framework Programme, explores new grounds in the molecular underpinnings of AD. The use of cutting-edge and innovative approaches (CRISPR/Cas9 gene editing, iPSC reprogramming, RNA-Seq analysis, high-throughput screening, and subcellular calcium imaging) provides a novel experimental model that is closer to the pathological processes of the AD brain and bypasses the limitations and shortcomings of preclinical AD animal models.
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 dementia alzheimer
- medical and health sciences medical biotechnology genetic engineering gene therapy
- natural sciences chemical sciences inorganic chemistry alkaline earth metals
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics mutation
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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-2018
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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.
66100 Chieti
Italy
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.