SweetBrain
Financiado
A new perspective on the metabolic pathway to neuronal dysfunction Using organs...
A new perspective on the metabolic pathway to neuronal dysfunction Using organs on a chip to elucidate the role of the brain microvasculature
Despite decades of research, the underpinnings of central nervous system (CNS) diseases and clear pathways to effective treatment remain elusive, mainly because of a scarcity of adequate models and methods with the capacity to elu...
Despite decades of research, the underpinnings of central nervous system (CNS) diseases and clear pathways to effective treatment remain elusive, mainly because of a scarcity of adequate models and methods with the capacity to elucidate human brain physiology. Recent studies suggest that high glucose levels are correlated with neuronal dysfunction and neurodegeneration, yet very little is known about the mechanisms of this relationship. Research in this vein has focused primarily on direct metabolic interactions between neurons and astrocytes, ignoring other cell populations in the neurovascular unit (NVU) that might have a meaningful role. My recent research revealed that the brain vasculature—the ‘gatekeeper’ through which all metabolites must pass to reach the neurons—has direct metabolic coupling with the neurons. Drawing from these observations, I adopt a previously unconsidered perspective and propose that the vasculature drives the neurodegenerative effects of hyperglycemia. Specifically, I hypothesize that high glucose levels change the metabolic function of the brain vasculature, thereby altering the direct endothelium-neuronal crosstalk and triggering neuronal dysfunction. To investigate this hypothesis, I will develop cutting-edge Organ-on-a-Chip (OoC) technology that overcomes the limitations of modeling NVU functionality and cell-cell interactions. Specifically, I will:
(1) establish a human-relevant NVU-OoC model for metabolic and functional interactions, in which different cell types grow separately while remaining metabolically and functionally coupled;
(2) identify the major metabolic and functional interactions in the human NVU at homeostasis and under diabetic conditions; and subsequently (3) target the vasculature communications to diminish neuronal dysfunction. This research has the potential to revolutionize the study of CNS disease, pointing to an unexplored pathway to a cure, and illuminating fundamental questions regarding brain metabolism.
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Duración del proyecto: 70 meses
Fecha Inicio: 2019-10-02
Fecha Fin: 2025-08-31
Fecha Fin: 2025-08-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2019-10-02
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2019-STG:
ERC Starting Grant
Cerrada
hace 6 años
Presupuesto
El presupuesto total del proyecto asciende a
1M€
Líder del proyecto
TEL AVIV UNIVERSITY
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
314.70K€ |
Participante