Innovating Works

AstroSignals

Financiado
Spatiotemporal dynamics of subcellular energy metabolism in astrocytes
The functional significance of subcellular compartmentalization in signal transduction has emerged in recent years, a development that is gaining momentum due to significant advances in optical microscopy and genetically encoded b... The functional significance of subcellular compartmentalization in signal transduction has emerged in recent years, a development that is gaining momentum due to significant advances in optical microscopy and genetically encoded biosensors. However, much less attention has been given to the spatial architecture of the metabolic networks that provide energetic support for intracellular processes. This project will investigate spatiotemporal organization of energy metabolism in astrocytes, focusing on two hypotheses: • I propose that within astrocytes, signalling microdomains are energetically supported by local delivery of ATP. I will employ confocal and total internal reflection fluorescence (TIRF) microscopy, using biosensors for ATP, glucose and Ca2+ that can be targeted to subcellular locations. My initial focus is on cultured human astrocytes and the provision of ATP for Ca2+ signalling. Do the five cellular sources of astrocytic ATP support different ATP pools? Which pools are needed for the many ATP-requiring steps that link cell-surface receptors to Ca2+ signals? • I suggest that the ER lumen may provide a glucose reservoir that allows rapid intracellular transfer of glucose to meet local energy needs. The ER of astrocytes contains luminal glucose-6-phosphatase-β (G-6-Pase-β) and a glucose-6-phosphate transporter, which together can generate an ER luminal pool of glucose. The source of glucose-6-phosphate transported into the ER and the function of luminal glucose are unknown. Using cytosolic and ER-targeted glucose sensors, immunocytochemistry and siRNA knockdown of glucose G-6-Pase-β, I will determine the source of the glucose pool and whether it contributes to metabolic support of Ca2+ signals. Combining state-of-the-art techniques and expertise in the fields of cell signalling and metabolism, this project will enhance our understanding of metabolic regulation of signal transduction, opening new possibilities for targeted treatments of brain diseases. ver más
31/03/2017
THE CHANCELLOR MAS...
183K€
Duración del proyecto: 24 meses Fecha Inicio: 2015-03-18
Fecha Fin: 2017-03-31

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2017-03-31
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
MSCA-IF-2014-EF: Marie Skłodowska-Curie Individual Fellowships (IF-EF)
Cerrada hace 10 años
Presupuesto El presupuesto total del proyecto asciende a 183K€
Líder del proyecto
THE CHANCELLOR MASTERS AND SCHOLARS OF THE UN... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5