SERPINOPATHIES

Determination of the structure of the pathological neuroserpin polymer and development of an intrabody strategy to prevent disease-associated inclusions in cell and animal models of disease

 Coordinatore UNIVERSITY COLLEGE LONDON 

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

contact info
Titolo: Ms.
Nome: Kamila
Cognome: Kolasinska
Email: send email
Telefono: +44 2031083033

 Nazionalità Coordinatore United Kingdom [UK]
 Totale costo 200˙371 €
 EC contributo 200˙371 €
 Programma FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call FP7-PEOPLE-2011-IEF
 Funding Scheme MC-IEF
 Anno di inizio 2013
 Periodo (anno-mese-giorno) 2013-03-01   -   2015-02-28

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    UNIVERSITY COLLEGE LONDON

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

contact info
Titolo: Ms.
Nome: Kamila
Cognome: Kolasinska
Email: send email
Telefono: +44 2031083033

UK (LONDON) coordinator 200˙371.80
2    THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE

 Organization address address: The Old Schools, Trinity Lane
city: CAMBRIDGE
postcode: CB2 1TN

contact info
Titolo: Ms.
Nome: Renata
Cognome: Schaeffer
Email: send email
Telefono: +44 1223 333543
Fax: +44 1223 332988

UK (CAMBRIDGE) participant 0.00

Mappa


 Word cloud

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

anti    disorders    proteins    polymer    serpinopathies    tissue    prevent    diseases    disease    antibody    deposition    monoclonal    conformational    inclusions    mutants    neuroserpin    intracellular   

 Obiettivo del progetto (Objective)

'An increasing number of human disorders are recognised to result from the aggregation and tissue deposition of misfolded proteins. This group of diseases has been termed the conformational disorders and comprises such diseases as Alzheimer’s, Huntington’s and Parkinson’s disease as well as the amyloidoses and the serpinopathies. The serpinopathies are characterized by the polymerisation and tissue deposition of mutants of members of the serine protease inhibitor or serpin superfamily of proteins. One of the most striking serpinopathies is familial encephalopathy with neuroserpin inclusion bodies (FENIB) that is caused by one of six naturally occurring point mutations in the neuroserpin gene. Mutant neuroserpin forms ordered polymers that accumulate within the endoplasmic reticulum of neurons, resulting in progressive dementia, with the age of onset of disease being inversely proportional to the rate of polymer formation in vitro and the number of intra-cerebral inclusions. This study will use an anti-polymer monoclonal antibody to (i) define the structure of the pathological neuroserpin polymer and its time-dependent appearance in the ER and (ii) as the basis for an intrabody strategy to prevent the inclusions associated with disease. First, regions of neuroserpin that are exposed upon transition from monomer to polymer will be analyzed by epitope mapping using differential chemical modification and crystallization aided by an antibody-engineered construct. Second, the ability of this anti-polymer monoclonal antibody to prevent pathogenic polymer formation and to impact their intracellular localization pattern will be assessed by co-expression with different neuroserpin mutants in cell and fly models of disease. The protective efficacy in vivo will be addressed by analyzing the locomotor phenotype in flies. If successful, an intracellular antibody based approach may be used to treat the serpinopathies and other ‘gain of function’ conformational diseases.'

Altri progetti dello stesso programma (FP7-PEOPLE)

ALLOPTICS (2012)

ALL-OPTIcal signal processing on-Chip in hybrid III-V/ Si integrated platforms

Read More  

FIRE TOOLS (2013)

Simulation of fire technical properties of products and construction barriers to support efficient product development in industry

Read More  

SHALOM (2014)

Explosive phenomena in the Universe: Gamma-Ray Bursts and SuperNovaRemnants as high-energy particle acceleration sites

Read More