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Microglia action towards neuronal circuit formation and function in health and disease

Objective

Constructing a neuronal circuit requires a firework of developmental events: First, the desired cell types have to be generated and wired correctly. Random propagating burst of action potentials among neighboring cells are shaping the functional maturation of these cell types, which later will be activity-dependent refined. Microglia are exposed to this environment from the beginning and show throughout development a morphological “activated”, phagocytic state. However, microglia have been proven to be involved in synapse refinement, which leads to the question how do microglia know when to alter neuronal circuit elements during development without inducing circuit malfunction? This is a fundamental question because the microglia activation state during development is intriguingly similar to the activation state in neurodegenerative diseases. To address this question, I use the retina as a model and propose the following three aims: First, we will reveal how the functional and gene regulatory network of microglia are altered when they are exposed to the neuronal activity-dependent environment and identify neuronal-imposed developmental checkpoints. We will study whether alteration of microglia function in this system will impact circuit formation and function. Second, we will examine microglia dynamics upon sequential removal of neuronal cell types in disease conditions and investigate whether functional restoration of cell types using optogenetic techniques resets microglia function. Third, we will establish the role of healthy and diseased microglia in human retinal circuit formation by reprogramming microglia and 3D-retinoids from healthy and diseased human iPS cells. I predict that my findings provide crucial insights into the functional impact of microglia upon both normal development and function, as well as how their actions may lead to disease phenotypes in situations of neurodegenerative diseases.

Fields of science (EuroSciVoc)

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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)

Programme(s)

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.

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.

ERC-STG - Starting Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2016-STG

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Host institution

INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA
Net EU contribution

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.

€ 1 500 000,00
Address
Am Campus 1
3400 KLOSTERNEUBURG
Austria

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Region
Ostösterreich Niederösterreich Wiener Umland/Nordteil
Activity type
Higher or Secondary Education Establishments
Links
Total cost

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.

€ 1 500 000,00

Beneficiaries (1)

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