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Design of artificial organelles to modulate the astrocyte-neuron communication

Project description

Engineering astrocytes for brain health

The brain relies on a complex vascular network, with the neurovascular unit (NVU) acting as the critical link between the brain and its blood vessels. This unit maintains the blood-brain barrier and supplies nutrients to neurons. Astrocytes, key cells in the NVU, mediate communication between neurons and endothelial cells, playing a vital role in brain health. The astrocyte-neuron lactate shuttle is crucial for brain homeostasis. Supported by the Marie Skłodowska-Curie Actions programme, the ANCOM project explores engineering astrocytes to enhance their interaction with neurons in a paper-based NVU model. By designing artificial organelles with silica nanoparticles and lactate dehydrogenase, the project aims to boost lactate production, advancing brain therapies.

Objective

The brain is supplied by a complex and vast vascular network whose interactions are difficult to grasp in their entirety. The neurovascular unit (NVU) was thus introduced and represents the minimal functional unit linking the brain and its vessels. NVU cells interact closely to maintain the integrity of the blood-brain barrier and supply the brain with nutrients. Among these, astrocytes play the key role of mediator between the endothelial cells, supporting the blood flow, and the neurons. The astrocyte-neuron lactate shuttle is an essential communication pathway, and its control is crucial for brain homeostasis and thus brain health.
The research hypothesis of ANCOM is that the engineering of astrocytes will allow to modulate their communication with neurons in close proximity, cultured in a paper-based NVU model. Engineered astrocytes can thereby be used to influence neurons’ behaviour and thus contribute to tune the brain’s activity. Specifically, artificial organelles will be designed to boost the lactate production in the astrocytes. These will be made of silica nanoparticles with lactate dehydrogenase enzyme immobilised on their surface and placed in the cytosol of the astrocytes. Upon a boosted lactate release, a beneficial effect on neurons is predicted either in simple cell cocultures but also in more complex systems. For that purpose, a dynamic in vitro paper-based model of the NVU containing endothelial cells, pericytes, astrocytes and neurons will be established. Moreover, by employing a new approach developed by the Städler lab, it will even be possible to add active locomotion to these artificial organelles with the aim of targeting the astrocytes through the blood circulation. ANCOM aims thus at offering an easily accessible NVU model, able to address many questions in neuroscience, contributing to the development of brain therapies. This interdisciplinary project will allow me to broaden my skills and start my career as an independent researcher.

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

AARHUS UNIVERSITET
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.

€ 214 934,40
Address
NORDRE RINGGADE 1
8000 Aarhus C
Denmark

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Region
Danmark Midtjylland Østjylland
Activity type
Higher or Secondary Education Establishments
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Total cost

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