Knowing that the lysosomes contain a powerful cocktail of hydrolases capable of digesting cells and entire tissues, it is obvious that the maintenance of lysosomal membrane integrity is of utmost importance for all cells, and espe...
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31/01/2019
DCS
2M€
Presupuesto del proyecto: 2M€
Líder del proyecto
KRAEFTENS BEKAEMPELSE
No se ha especificado una descripción o un objeto social para esta compañía.
TRL
4-5
Fecha límite participación
Sin fecha límite de participación.
Financiación
concedida
El organismo FP7 notifico la concesión del proyecto
el día 2019-01-31
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Características del participante
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Información proyecto LYSOSOME
Líder del proyecto
KRAEFTENS BEKAEMPELSE
No se ha especificado una descripción o un objeto social para esta compañía.
TRL
4-5
Presupuesto del proyecto
2M€
Fecha límite de participación
Sin fecha límite de participación.
Descripción del proyecto
Knowing that the lysosomes contain a powerful cocktail of hydrolases capable of digesting cells and entire tissues, it is obvious that the maintenance of lysosomal membrane integrity is of utmost importance for all cells, and especially for cancer cells with dramatically increased lysosomal activity. Yet, the mechanisms that regulate lysosomal membrane stability have remained obscure, largely due to the lack of methods sensitive enough to detect partial lysosomal leakage and suitable for screening purposes. We have finally succeeded in developing such a method, which allows me to propose here a project whose major aim is to reveal how cells maintain the integrity of lysosomal membranes. Based on our emerging data that firmly connect heat shock protein 70 and sphingolipid metabolism to lysosomal membrane stability, we will devote a large part of the project to the molecular details of these connections and to the characterization of the effects of new and already approved (cationic amphiphilic drugs) sphingolipid-regulating drugs on lysosomal membrane stability and cell survival. Additionally, we will screen selected siRNA libraries to identify signaling networks and lysosome-associated proteins essential for lysosomal membrane integrity, and small molecule libraries to identify compounds that induce lysosomal cell death. The next step is to identify lysosome-stabilizing mechanisms that are especially important for cancer cell survival. And the ultimate goal is to validate corresponding drug targets and drugs (old and new) for the induction of lysosomal cell death in therapy resistant cancers. As a by-product we expect to identify putative drug targets for the treatment of degenerative diseases and lipid storage disorders, where the stabilization of the lysosomal membranes promotes cell survival.