NAD synthesizing enzyme NMNAT1 as a fine regulator of the survival of neuron

Projektinformationen

REGUNMNAT1

ID Finanzhilfevereinbarung: 627117

Abgeschlossenes Projekt

Startdatum 1 Oktober 2014

Enddatum 30 September 2016

Finanziert unter

• Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Gesamtkosten € 231 283,20

EU-Beitrag € 231 283,20

Koordiniert durch

THE UNIVERSITY OF NOTTINGHAM
United Kingdom

Ziel

We propose here to investigate the role of the nuclear NAD-synthesising enzyme nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) as a fine regulator of neuron survival, aiming at identifying new targets for intervention in age-associated pathological conditions of the nervous system. NAD synthesis is central to neuron maintenance and to the action of enzymes such as sirtuins (SIRTs), poly(ADP-ribose)polymerases (PARPs), NAD glycohydrolases and ADP-ribose cyclases, involved, via gene transcription or by signalling mechanisms, in the regulation of cell and organism lifespan, in the response of neurons to stress and in protection in models of neurodegenerative diseases. NMNAT’s involvement in these processes is rapidly emerging but has not been investigated in detail. Our preliminary studies indicate that nuclear isozyme NMNAT1 is required for neuron maintenance. Building on this, here we will test the hypothesis that NMNAT1 controls neuron survival by regulating the activity of downstream enzyme SIRT1. This project is based on the unique availability to the host laboratory of Nmnat1 genetically modified mice and on the perfect match between the expertise of the host laboratory and the complementary skills of the IEF applicant, Dr Jessica De Ingeniis, a talented researcher who has received extensive training in NAD biochemistry and metabolomics in Italy and USA. This study, which can only be accomplished by combining these skills of the IEF fellow with the mouse genetics and neurobiology expertise of the supervisor, will serve two crucial purposes. It will provide vital insights into the mechanisms of neuronal survival and the role of nuclear NAD biosynthesis, constituting a fundamental prelude to the development of specific inhibitors and activators of NMNAT1 with a pharmaceutical application; and it will fill important gaps in the competences of the IEF fellow representing a crucial, final step into the development of her independent research career.

Wissenschaftliches Gebiet

• natural sciences › biological sciences › neurobiology
• natural sciences › biological sciences › genetics
• natural sciences › biological sciences › biochemistry › biomolecules › proteins › enzymes

Programm/Programme

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Thema/Themen

• FP7-PEOPLE-2013-IEF - Marie-Curie Action: "Intra-European fellowships for career development"

Aufforderung zur Vorschlagseinreichung

FP7-PEOPLE-2013-IEF
Andere Projekte für diesen Aufruf anzeigen

Finanzierungsplan

MC-IEF - Intra-European Fellowships (IEF)

Koordinator

THE UNIVERSITY OF NOTTINGHAM

Kontakt Verwaltung

Paul Cartledge (Mr.)

• EU-Beitrag: € 231 283,20
• Adresse: University Park ; NG7 2RD Nottingham ; Vereinigtes Königreich
• Region: East Midlands (England) › Derbyshire and Nottinghamshire › Nottingham
• Aktivitätstyp: Higher or Secondary Education Establishments
• Gesamtkosten: Keine Daten