EUROSPIN

European Consortium on Synaptic Protein Networks in Neurological and Psychiatric Diseases

 Coordinatore MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V. 

 Organization address address: Hofgartenstrasse 8
city: MUENCHEN
postcode: 80539

contact info
Titolo: Prof.
Nome: Nils
Cognome: Brose
Email: send email
Telefono: +49 551 3899725
Fax: +49 551 3899715

 Nazionalità Coordinatore Germany [DE]
 Sito del progetto http://eurospin.mpg.de
 Totale costo 15˙806˙674 €
 EC contributo 11˙952˙691 €
 Programma FP7-HEALTH
Specific Programme "Cooperation": Health
 Code Call FP7-HEALTH-2009-single-stage
 Funding Scheme CP-IP
 Anno di inizio 2010
 Periodo (anno-mese-giorno) 2010-01-01   -   2014-06-30

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V.

 Organization address address: Hofgartenstrasse 8
city: MUENCHEN
postcode: 80539

contact info
Titolo: Prof.
Nome: Nils
Cognome: Brose
Email: send email
Telefono: +49 551 3899725
Fax: +49 551 3899715

DE (MUENCHEN) coordinator 2˙845˙290.00
2    THE UNIVERSITY OF EDINBURGH

 Organization address address: OLD COLLEGE, SOUTH BRIDGE
city: EDINBURGH
postcode: EH8 9YL

contact info
Titolo: Ms.
Nome: Angela
Cognome: Noble
Email: send email
Telefono: +44 131 650 9024
Fax: +44 131 650 9023

UK (EDINBURGH) participant 1˙948˙514.50
3    SYNAPTOLOGICS BV

 Organization address address: BURMANSTRAAT 7
city: AMSTERDAM
postcode: 1091 SG

contact info
Titolo: Mrs.
Nome: Evelyn
Cognome: Van Royen
Email: send email
Telefono: +31 20 5982806
Fax: +31 20 5987112

NL (AMSTERDAM) participant 988˙425.00
4    MAX-DELBRUCK-CENTRUM FUR MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT

 Organization address address: ROBERT ROSSLE STRASSE 10
city: BERLIN
postcode: 13125

contact info
Titolo: Ms.
Nome: Flügge
Cognome: Tanja
Email: send email
Telefono: +49 30 94063790
Fax: +49 30 94062581

DE (BERLIN) participant 692˙034.00
5    FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH

 Organization address address: MAULBEERSTRASSE 66
city: BASEL
postcode: 4058

contact info
Titolo: Ms.
Nome: Dorothy
Cognome: Searles
Email: send email
Telefono: +41 61 6972982
Fax: +41 61 6973976

CH (BASEL) participant 616˙439.00
6    STICHTING VU-VUMC

 Organization address address: DE BOELELAAN 1105
city: AMSTERDAM
postcode: 1081 HV

contact info
Titolo: Dr.
Nome: Yvonne
Cognome: Kops
Email: send email
Telefono: +31 20 5987304
Fax: +31 20 5989950

NL (AMSTERDAM) participant 587˙322.00
7    UNIVERSITY COLLEGE LONDON

 Organization address address: GOWER STREET
city: LONDON
postcode: WC1E 6BT

contact info
Titolo: Ms.
Nome: Greta
Cognome: Borg-Carbott
Email: send email
Telefono: +44 20 3108 3033
Fax: +44 20 3108 3096

UK (LONDON) participant 580˙307.00
8    UNIVERSITAET ZUERICH

 Organization address address: Raemistrasse 71
city: ZURICH
postcode: 8006

contact info
Titolo: Prof.
Nome: David P.
Cognome: Wolfer
Email: send email
Telefono: +41 44 635 5312
Fax: +41 44 635 5702

CH (ZURICH) participant 575˙200.00
9 Synaptic Systems DE participant 562˙987.00
10    UNIVERSITY OF HAIFA

 Organization address address: "Mount Carmel, Abba Khoushi Blvd."
city: HAIFA
postcode: 31905

contact info
Titolo: Ms.
Nome: Suzan
Cognome: Aminpour
Email: send email
Telefono: +972 4 8240549
Fax: +972 4 8288035

IL (HAIFA) participant 554˙748.00
11    UNIVERSITA DEGLI STUDI DI MILANO

 Organization address address: Via Festa Del Perdono 7
city: MILANO
postcode: 20122

contact info
Titolo: Dr.
Nome: Federica
Cognome: Tidone
Email: send email
Telefono: +39 02 50317072
Fax: +39 02 50317071

IT (MILANO) participant 478˙200.00
12    GENOME RESEARCH LIMITED

 Organization address address: THE GIBBS BUILDING, EUSTON ROAD 215
city: LONDON
postcode: NW1 2BE

contact info
Titolo: Mr.
Nome: David N
Cognome: Davison
Email: send email
Telefono: +44 1223 834244
Fax: +44 1223 494919

UK (LONDON) participant 452˙922.53
13    Synome Ltd

 Organization address address: MONETA BUILDING BABRAHAM RESEARCH CAMPUS
city: Cambridge
postcode: CB22 3AT

contact info
Titolo: Mr.
Nome: Troels
Cognome: Jordansen
Email: send email
Telefono: +44 1223 352200
Fax: +44 1223 281 399

UK (Cambridge) participant 325˙993.00
14    TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY

 Organization address address: TECHNION CITY - SENATE BUILDING
city: HAIFA
postcode: 32000

contact info
Titolo: Mr.
Nome: Jacob
Cognome: Lavan
Email: send email
Telefono: +972 4 8293097
Fax: +972 4 8232958

IL (HAIFA) participant 301˙440.00
15    RIKEN THE INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH

 Organization address address: HIROSAWA 2-1
city: WAKO SHI SAITAMA
postcode: 351 0198

contact info
Titolo: Mr.
Nome: Haruo
Cognome: Yamaguchi
Email: send email
Telefono: +81 48 4679299
Fax: +81 48 4624950

JP (WAKO SHI SAITAMA) participant 236˙735.50
16    MEDICAL RESEARCH COUNCIL

 Organization address address: NORTH STAR AVENUE POLARIS HOUSE
city: SWINDON
postcode: SN2 1FL

contact info
Titolo: Ms.
Nome: Claire
Cognome: Hebblethwaite
Email: send email
Telefono: +44 20 7679 7259
Fax: +44 20 7679 7805

UK (SWINDON) participant 206˙133.50
17    Novartis Forschungsstiftung

 Organization address address: Maulbeerstrasse 66
city: BASEL
postcode: 4058

contact info
Titolo: Ms.
Nome: Dorothy
Cognome: Searles
Email: send email
Telefono: +41 61 6972982
Fax: +41 61 6973976

CH (BASEL) participant 0.00
18    VERENIGING VOOR CHRISTELIJK HOGER ONDERWIJS WETENSCHAPPELIJK ONDERZOEK EN PATIENTENZORG

 Organization address address: De Boelelaan 1105
city: AMSTERDAM
postcode: 1081 HV

contact info
Titolo: Ms.
Nome: Els
Cognome: Borghols
Email: send email
Telefono: +31 20 5986925
Fax: +31 20 5986926

NL (AMSTERDAM) participant 0.00

Mappa


 Word cloud

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

outcomes    validated    purification    interactions    protein    coding    ko    neurological    electrophysiological    genes    lines    imaging    eurospin    mouse    mechanisms    plasticity    disorders    gene    small    ppi    cell    molecules    mutations    fear    tested    diagnostic    proteins    biology    networks    patients    tools    hypotheses    disease    screens    nlgn    synaptic    signalling    synapses    snap    causation    adhd    mice    synaptopathies    therapies    therapeutic    dysfunction    psychiatric    diseases    models    transmission    behavioural    function    techniques   

 Obiettivo del progetto (Objective)

'Signalling at nerve cell synapses - a key determinant of all aspects of brain function - depends on the function of hundreds of synaptic proteins and their interactions. Numerous recent studies showed that a wide range of neurological and psychiatric diseases are 'synaptopathies' whose onset and progression are due to mutations of synaptic proteins and subsequent synaptic dysfunctions. EUROSPIN will pursue a multilevel systems biology approach to determine mechanistic relationships between mutations of synaptic proteins and neurological and psychiatric diseases, and to develop new diagnostic tools and therapies. Our concept is based on the current knowledge of disease genes, which we will continuously extend with new human genetic data and complement with large-scale screens of mutant mice in order to identify and characterize disease-relevant mutations in synaptic proteins and corresponding mouse models. Proteomic tools will be used to analyse the protein components of synapses, and protein interaction networks of synaptic disease gene products will be mapped systematically. In parallel, smart libraries will be employed to develop small molecules for perturbing the functions and interactions of disease gene products. Functional models of disease-relevant protein networks will be generated and used to formulate hypotheses as to how specific mutations might affect synaptic physiology and network function, and thus cause disease. These hypotheses will initially be tested in reduced systems by novel physiological and imaging methods. Well-validated disease gene products, the consequences of their dysfunction in disease, and therapeutic modifications of their dysfunction will then be studied in mouse models in vivo, applying novel electrophysiological, imaging, and behavioural techniques. The combined information obtained in the EUROSPIN program will be used for the development of new diagnostic tools and therapeutic interventions that can be tested in patients.'

Descrizione progetto (Article)

Mutations in genes coding for synaptic proteins are involved in the causation of neurological and psychiatric disorders, but a comprehensive understanding of the molecular processes leading to disease is still lacking. The EU-backed 'European consortium on synaptic protein networks in neurological and psychiatric diseases' (http://www.eurospin.mpg.de/ (EUROSPIN)) project aimed at improving understanding of the mechanisms leading to synaptopathies.

A multi-level systems biology approach was used to unravel the mechanisms linking mutations in genes coding for synaptic proteins to the occurrence of neurological and/or psychiatric disorders. Such an approach relies on a wide range of disciplines and techniques, spanning from biochemistry to behavioural studies. Through an improved understanding of disease causation, the consortium delivered novel leads for diagnostic tools and therapies of synaptopathies.

Scientists completed large-scale screens of protein-protein interactions (PPIs) of 1 340 synaptic proteins and generated PPI networks of 7 677 interactions. Moreover, mice lines were created that expressed tandem affinity purification-tagged synaptic proteins for several applications such as protein purification and screening of substrates. An antibody production pipeline enabled protein expression and localisation studies. In combination, these are very useful tools to study synaptic protein complexes and aberrant PPI changes in disease models.

Eighteen validated mouse lines representing different synaptopathies (e.g. SNAP-25 knockout (KO) mice for attention deficit hyperactivity disorder (ADHD)) were used to analyse synaptic transmission and plasticity as well as behaviour. Additionally, cell biological and electrophysiological studies were carried out on disease-relevant synaptic proteins such as SNAP25, Munc18-1 and NLGN-2.

An important finding was that antiepileptic drugs could be useful in ADHD treatment. Using behavioural analyses, neuronal circuits in fear conditioning were characterised to assess plasticity and learning in mice models. Interestingly, NLGN-2 KO mice were unable to acquire fear in response to certain stimuli due to reduced inhibitory synaptic transmission in the amygdala.

Studies revealed that a subset of 1 026 synaptic genes rather than an individual gene causes schizophrenia by affecting signal transduction, synaptic excitability, cell adhesion and trans-synaptic signalling. Small molecules were synthesised that affected the aggregation of beta-amyloid peptides commonly seen in Alzheimer's disease that could prove effective in therapy.

Project outcomes could now enable the synthesis of small molecules that can effectively treat synaptopathies and restore normal function. Besides placing the EU ahead in the biomedical sector, project outcomes will improve patients' quality of life while reducing the socioeconomic burdens caused by synaptopathies.

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