WTBLDOHRNCE

Walking the tightrope between life and death: Oxygen homeostasis regulation in the nematode Caenorhabditis elegans

Coordinatore	THE HEBREW UNIVERSITY OF JERUSALEM.    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Israel [IL]
Totale costo	1˙495˙922 €
EC contributo	1˙495˙922 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2011-StG_20101109
Funding Scheme	ERC-SG
Anno di inizio	2011
Periodo (anno-mese-giorno)	2011-11-01   -   2016-10-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	THE HEBREW UNIVERSITY OF JERUSALEM.  Organization address address: GIVAT RAM CAMPUS city: JERUSALEM postcode: 91904 contact info Titolo: Dr. Nome: Einav Cognome: Gross Email: send email Telefono: +972 2 6758282 Fax: +972 2 6439736	IL (JERUSALEM)	hostInstitution	1˙495˙922.00
2	THE HEBREW UNIVERSITY OF JERUSALEM.  Organization address address: GIVAT RAM CAMPUS city: JERUSALEM postcode: 91904 contact info Titolo: Mr. Nome: Hani Cognome: Ben-Yehuda Email: send email Telefono: +972 2 6586676 Fax: +972 7 22447007	IL (JERUSALEM)	hostInstitution	1˙495˙922.00

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 Obiettivo del progetto (Objective)

'Oxygen (O2) is vital for the life of all aerobic animals. However, fine-tuned regulation of O2 levels is crucial since both shortage (hypoxia) and excess (via the production of reactive oxygen species, ROS) may be harmful. Indeed, both hypoxia and ROS may underlie the pathophysiology of many diseases such as atherosclerosis and Alzheimer’s. To understand how this fine-tuned O2 regulation is achieved at both the molecular and organismal levels my research proposal aims to explore the following integrated questions, using the nematode C. elegans as a model organism. 1) How do animal sense O2? What are the molecular sensors and how do they act together to fine-tune O2 responses? 2) How does O2 regulate food intake, and repress appetite in hypoxia? 3) How do animals survive and behaviorally adapt to hypoxia without HIF-1? 4) How hydrogen sulfide (H2S) regulates O2 responses and aging? 5) How do animals protect against mRNA oxidation damage? I have focused my research on the globins. GLB-5 is a C. elegans hexacoordinated globin that regulates foraging behavior in response to subtle changes in O2 concentration. Like neuroglobin and cytoglobin in our brain, GLB-5 is expressed in neurons. Recently I discovered that GLB-5 regulates the re-adaptation of animals to 21% O2 after hypoxia. To understand how GLB-5 regulates hypoxia-reoxygenation responses I made a mutagenesis screen and isolated four classes of GLB-5 suppressors, and mapped them using single-nucleotide polymorphisms (SNP’s) to about a 1 Mbp genomic interval. Using a novel non-PCR based libraries preparation and Next Generation whole-genome sequencing, I have already sequenced four independent mutations and cloned one of the GLB-5 suppressors. In the future, I intend to clone more suppressor genes, and use this methodology in other parts of my project. By doing so, I aim to understand O2 homeostasis regulation at all levels; from the molecular signaling network to the physiology and behavior of the whole animal.'