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GSL in development

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The role of glycosphingolipids in development

Glycosphingolipids have been implicated in the development of various human pathologies, such as cancer, obesity, diabetes or Alzheimer diseases. Their wide implication in cellular membrane architecture and cellular signaling netw... ver más

30/09/2013

63K€

Presupuesto del proyecto: 63K€

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INSTITUT PASTEUR No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

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Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2013-09-30 No tenemos la información de la convocatoria

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Líder del proyecto

INSTITUT PASTEUR No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 63K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Glycosphingolipids have been implicated in the development of various human pathologies, such as cancer, obesity, diabetes or Alzheimer diseases. Their wide implication in cellular membrane architecture and cellular signaling network and metabolism has however made difficult the establishment of an integrated and accurate understanding of their role in vivo. The current proposal aims to understand such a role by taking advantage of a highly versatile system model, the Drosophila melanogaster. By combining sophisticated genetic and biochemical approaches with cutting edge biophysical strategies, such as FRET or FRAP technologies, this proposal intends to 1) determine how GSLs affect the dynamic organization of membranes at the nanoscale resolution in vivo, 2) study the GSL impact on cellular signaling and 3) polarity and finally 4) uncover some putative molecular regulators of GSL function in vivo. Preliminary work in Drosophila embryos allowed us to demonstrate that the absence of core GSLs in two related lethal mutants, egghead (egh) and brainiac (brn), leads to a surprisingly specific phenotype consisting in an increased number of proprioceptive organs. During the eclosion process, flies lacking core GSLs are unable to organize their movements and dies within the pupae case. Interestingly, Brn protein expression in brn flies using the UAS/GAL4 system in proprioception organs rescues their phenotype. We hence intend to take advantage of these rescue conditions to screen for molecular factors allowing to compensate the absence of core GSLs. Finally, the increased in proprioceptive organs being typically associated to an upregulation of the EGFR pathway, we aim to understand its genetic relationship of brn and egh mutations. This comprehensive characterization of the role of core GSLs in vivo will certainly constitute an important step in order to further evaluate the nature of their function in Drosophila models of human diseases in the near future.

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