NEoC – NeuroEnergetics-on-Chip: Disease modeling of impaired brain glucose metab...
NEoC – NeuroEnergetics-on-Chip: Disease modeling of impaired brain glucose metabolism using human iPSC-derived neurovascular units (NVU)-on-chip systems
Neurological conditions conquer the world; they are the leading cause of disability and second leading cause of death worldwide. Although there is growing evidence for the immense impact of disturbances in neurometabolism for over...
Neurological conditions conquer the world; they are the leading cause of disability and second leading cause of death worldwide. Although there is growing evidence for the immense impact of disturbances in neurometabolism for overall brain function, only little is known about the underlying mechanisms (knowledge gap). Especially human insights are sparse due to a paucity of physiologically relevant model systems (research gap).
To address these challenges, within the scope of the NeuroEnergetics-on-Chip (NEoC) project, I am proposing the development of a novel, human iPSC-based organ-on-chip model of the neurovascular unit (NVU) that integrates all neurometabolically active NVU cell types and specifically enables the inspection of neurometabolic coupling mechanisms. To categorically cast light onto the mechanisms behind impaired metabolism of glucose, the brain’s principal energy supplier, I will build an NVU-on-Chip disease model of glucose transporter 1 deficiency syndrome (GLUT1-DS). Since GLUT1-DS is monogenic, it presents an excellent paradigm to study cellular and molecular consequences of disturbed neuroenergetics, even beyond the disease itself.
For implementation of the NEoC project, I will i) generate all neurometabolically relevant NVU cell types (endothelial cells, perivascular cells, astrocytes, microglia and neurons) from human iPSC lines derived from GLUT1-DS patients, ii) develop a novel NVU microfluidic platform addressing the shortcomings of existing NVU-on-Chip systems, and iii) build GLUT1-DS-NVU-on-Chip models to specifically study perturbations in energy metabolism, blood-brain barrier integrity and neuroinflammation as a consequence of GLUT1-DS in vitro.
The NEoC project will provide novel knowledge on the underlying mechanisms and pathophysiology of GLUT1-DS, and thereby not only benefit those afflicted by the orphan disease but impact our understanding of a variety of other CNS and metabolically linked disorders.ver más
Seleccionando "Aceptar todas las cookies" acepta el uso de cookies para ayudarnos a brindarle una mejor experiencia de usuario y para analizar el uso del sitio web. Al hacer clic en "Ajustar tus preferencias" puede elegir qué cookies permitir. Solo las cookies esenciales son necesarias para el correcto funcionamiento de nuestro sitio web y no se pueden rechazar.
Cookie settings
Nuestro sitio web almacena cuatro tipos de cookies. En cualquier momento puede elegir qué cookies acepta y cuáles rechaza. Puede obtener más información sobre qué son las cookies y qué tipos de cookies almacenamos en nuestra Política de cookies.
Son necesarias por razones técnicas. Sin ellas, este sitio web podría no funcionar correctamente.
Son necesarias para una funcionalidad específica en el sitio web. Sin ellos, algunas características pueden estar deshabilitadas.
Nos permite analizar el uso del sitio web y mejorar la experiencia del visitante.
Nos permite personalizar su experiencia y enviarle contenido y ofertas relevantes, en este sitio web y en otros sitios web.