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Contenuto archiviato il 2024-05-30

Prenylated protein regulation in the Caenorhabditis elegans brain

Obiettivo

"Protein prenylation is essential for the viability of all eukaryotic cells. Prenylated proteins regulate fundamental processes such as cell growth, differentiation and movement. Therefore, it is not surprising that prenylated proteins play a critical role in the pathophysiology of human diseases such as cancer and atherosclerosis. Indeed, mutations in the farnesylated oncogene Ras are found in 10-15% of all human tumors. Recent studies demonstrated that PDE6D acts as a soluble chaperon of Ras, thus it might regulate its oncogenic activity. In addition, PDE6D is important for the efficient transport of the rhodopsin kinase GRK1 and the alpha and beta subunits of PDE6 from the ER to the outer segments of cones and rods cells. Thus may play a critical role in normal vision physiology. PDE6D is conserved and has homologs across the animal kingdom. In the C. elegans worm, RNAi experiments against the PDE6D homolog pdl-1 failed to produce any abnormalities in the nematode physiology or behavior. However, we isolated a pdl-1 suppressor mutant that inhibits the fast recovery of worms after hypoxic stress.
We demonstrated that pdl-1 regulate the correct localization of the O2 sensor gcy-35. Thus, pdl-1 is essential for normal O2 responses in the C. elegans worm. Based on those finding my research proposal aims to:
1) Understand how pdl-1 is transported inside cells and elucidate novel regulators of its activity.
2) Identify new PDL-1 substrates, and explore their function in the C. elegans brain.
Hence, my research proposal aim is to understand protein prenylation regulation at all levels; from the molecular signaling network to the physiology and behavior of the whole animal. For this aim, we use behavioral paradigms together with state of the art microscopy, biochemistry and computational methods. We hope that our studies will strengthen the prenylated protein field in Europe and assist in development of better therapies for cancer, and atherosclerosis diseases."

Invito a presentare proposte

FP7-PEOPLE-2012-CIG
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Coordinatore

THE HEBREW UNIVERSITY OF JERUSALEM
Contributo UE
€ 100 000,00
Indirizzo
EDMOND J SAFRA CAMPUS GIVAT RAM
91904 Jerusalem
Israele

Mostra sulla mappa

Tipo di attività
Higher or Secondary Education Establishments
Contatto amministrativo
Hani Ben Yehuda (Ms.)
Collegamenti
Costo totale
Nessun dato