PREPOBEDIA

NOVEL PREP1-DEPENDENT TRANSCRIPTIONAL NETWORKS IN THE CONTROL OF INSULIN SENSITIVITY

 Coordinatore IFOM FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE 

 Organization address address: "Via Adamello, 16"
city: MILAN
postcode: 20139

contact info
Titolo: Ms.
Nome: Raffaela
Cognome: Zoboli
Email: send email
Telefono: +39 02 574303202
Fax: +39 02 574303231

 Nazionalità Coordinatore Italy [IT]
 Sito del progetto http://www.prepobedia.org/
 Totale costo 3˙159˙629 €
 EC contributo 2˙390˙983 €
 Programma FP7-HEALTH
Specific Programme "Cooperation": Health
 Code Call FP7-HEALTH-2007-A
 Funding Scheme CP-FP
 Anno di inizio 2008
 Periodo (anno-mese-giorno) 2008-01-01   -   2012-06-30

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    IFOM FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE

 Organization address address: "Via Adamello, 16"
city: MILAN
postcode: 20139

contact info
Titolo: Ms.
Nome: Raffaela
Cognome: Zoboli
Email: send email
Telefono: +39 02 574303202
Fax: +39 02 574303231

IT (MILAN) coordinator 0.00
2    Nome Ente NON disponibile

 Organization address address: YLIOPISTONRANTA 1 E
city: Kuopio
postcode: 70211

contact info
Titolo: Ms.
Nome: Janna
Cognome: Backman
Email: send email
Telefono: 358506000000
Fax: 35817162187

FI (Kuopio) participant 0.00
3    CONGENIA SRL

 Organization address address: VIA GIOVANNINO DE GRASSI 11
city: MILANO
postcode: 20123

contact info
Titolo: Prof.
Nome: Saverio
Cognome: Minucci
Email: send email
Telefono: +39 02 57489855
Fax: +39 02 94375990

IT (MILANO) participant 0.00
4    DEUTSCHES INSTITUT FUER ERNAEHRUNGSFORSCHUNG POTSDAM REHBRUECKE

 Organization address address: Arthur-Scheunert-Allee 114-116
city: NUTHETAL
postcode: 14558

contact info
Titolo: Dr.
Nome: Judith
Cognome: Schaefer
Email: send email
Telefono: +49 33200 88292
Fax: +49 33200 88509

DE (NUTHETAL) participant 0.00
5    UNIVERSITA DEGLI STUDI DI NAPOLI FEDERICO II.

 Organization address address: Corso Umberto I 40
city: NAPOLI
postcode: 80138

contact info
Titolo: Mr.
Nome: Giuseppe
Cognome: Crispo
Email: send email
Telefono: +39 081 7463042
Fax: +39 081 7701016

IT (NAPOLI) participant 0.00

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

ppar    absence    showed    components    genes    decreased    mouse    pgc    adipogenesis    obesity    sensitivity    alpha    prep    prepobedia    metabolic    function    energy    homeostasis    insulin    involvement    cellular    gene       levels    investigations    genetics    human    syndrome    indeed    functions    inhibitor    susceptibility    transgenic    impact    failed    health    mice    molecular    dependent    genetic    mbp    mechanisms    diabetes    humans    affected    expression    gamma    coactivator   

 Obiettivo del progetto (Objective)

'Type 2 diabets and obesity are related conditions representing major components of the metabolic syndrome and one of the most challenging health problems of this century, also because of their growing impact in childhood. Different studies have identified PPAR-gamma coactivator-1 (PGC-1alpha) as a relevant type 2 diabetes susceptibility gene playing an important role in human obesity as well. Subsequent investigations led to the discovery that p160MBP (MybBindingProtein) serves as a PGC-1alpha inhibitor. More recently, we showed that p160MBP is controlled by the Prep1 gene. Prep1 hypomorphic mice feature increase sensitivity to insulin due to raised PGC-1 alpha and decreased p160MBP levels. These mice also exhibit decreased fat body mass. Indeed, we also identified Prep1 in genetic screenings in C. Elegans and mouse ,as a major gene involved in energy homeostasis and obesity. Importantly, we have preliminary data showing Prep1 overexpression in euglycemic first-degree relatives of type 2 diabetics, which are at very high risk of diabetes. This project aims at understanding how Prep1 gene controls insulin sensitivity and determines adipogenesis, obesity and type 2 diabetes in humans. We will: 1: elucidate the molecular basis of Prep1 role in insulin sensitivity and adipogenesis through in vitro and animal model studies; 2: assess the significance of Prep1 function to insulin sensitivity in humans and the role of this gene in type 2 diabetes and its subphenotypes and in other components of the metabolic syndrome; 3: identify Prep1 target genes and establish their potential as targets for novel strategies to treat type 2 diabetes and metabolic syndrome. To achieve these objectives we have built a multidisciplinary network and gathered experts in the Prep1/p160MBP signaling, type 2 diabetes and obesity molecular biology and genetics, human and mouse genetics and high throughput analysis of gene expression and identification of target genes.'

Introduzione (Teaser)

Type 2 diabetes and obesity are considered to be the predominant metabolic syndromes of developed countries. A European consortium investigated the potential role of transcription factors in the development of these metabolic diseases.

Descrizione progetto (Article)

Apart from diet, accumulating evidence indicates the involvement of the PPAR-gamma coactivator-1 (PGC-1alpha) as a susceptibility gene in type 2 diabetes and obesity. Previous work by the Prepobedia consortium members showed that the expression of the PGC-1 alpha gene inhibitor (p160MBP) is controlled by the Prep1 gene, a key factor of pancreas development and function. Transgenic animals expressing lower levels of the Prep1 gene showed an increase in sensitivity to insulin, implicating it in energy homeostasis and obesity.

Aiming to advance knowledge on the Prep1 gene, the EU-funded 'Novel prep1-dependent transcriptional networks in the control of insulin sensitivity' (Prepobedia) project focused on delineating the molecular mechanisms of its function. Using specific Prep1 transgenic mice, researchers unveiled the role of the protein in lipid metabolism.

RNA and chromatin immunoprecipitation (ChIP) analysis of mouse embryos identified Prep1 target genes and facilitated investigations into the impact of Prep1 absence or mutation. Results indicated that Prep1 affected, in particular, basic cellular mechanisms and important genes, including Homeobox (Hox) genes.

Large-scale human genetic analysis failed to identify the Prep1 gene as a putative cause of at least some cases of type 2 diabetes or obesity. The reason was that Prep1 affected more essential functions, which obscured downstream effects.

Indeed, complete absence of Prep1 was shown to drive cells to apoptosis under conditions of DNA damage in a p53-dependent way. This observation drove scientists to investigate Prep1 in cancer, revealing a novel capacity of the gene to act as a tumour suppressor.

The Prepobedia study unravelled novel aspects of the Prep1 gene functions and identified its involvement in important cellular processes. Although it failed to reveal a concrete association with metabolic disorders, the generated information should enable a better understanding of how Prep1 mutations may affect human health.

Altri progetti dello stesso programma (FP7-HEALTH)

COLTHERES (2011)

Modelling and predicting sensitivity to targeted therapies in colorectal cancers

Read More  

KIEKIDS (2011)

Development of an innovative paediatric formulation of an antiepileptic agent for the treatment of absence epilepsy in children

Read More  

LEISHDRUG (2008)

Targeting the Leishmania kinome for the development of novel anti-parasitic strategies

Read More