Summary
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.
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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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101152165 |
| Start date: | 01-05-2024 |
| End date: | 30-04-2026 |
| Total budget - Public funding: | - 214 934,00 Euro |
Cordis data
Original description
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.
Status
SIGNEDCall topic
HORIZON-MSCA-2023-PF-01-01Update Date
01-01-2025
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