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Anti-Parasitic Drug Discovery in Epigenetics

Objective

This proposal builds on the proven methodology developed in the SEtTReND FP7 project to develop inhibitors of schistosome HME as lead compounds for new drugs. We will employ a target-based strategy for the development of novel drug leads against schistosomiasis, leishmaniasis, Chagas disease and malaria by targeting histone modifying enzymes (HME), in particular those involved in acetylation/deacetylation and methylation/demethylation. The principal objectives of A-PARADDISE are:
- The identification of HMEs from Leishmania sp. and Trypanosoma cruzi and the molecular characterization and functional characterization of selected potential targets,
- Phenotypic screening of Leishmania, T. cruzi, S. mansoni and P. falciparum using HME class inhibitors, inhibitors developed specifically against S. mansoni and P. falciparum HMEs. This will permit us to obtain a comprehensive view of inhibitor classes and chemical scaffolds of interest,
- Production of recombinant Leishmania and T. cruzi HME proteins, structural studies. Selected, validated target enzymes will be produced, crystallized and analysed by X-ray diffraction. Assays will be optimized to permit testing of inhibitors,
- High-throughput and structure-based (in silico) screening of selected HMEs. Inhibitors selected will be further screened by phenotypic assays on the parasites in vitro,
- Optimisation of inhibitor structures by chemical synthesis based on molecular modelling studies (inhibitors of all origins),
- Transcriptomic analysis of drug-treated parasites to verify target specificity and mechanism of action (all parasites),
- Pharmacological and toxicological studies (in vitro and in vivo) of selected inhibitors, in vivo testing of compounds in parasite-infected mice.
The overall objective of the A-PARADDISE project is to develop optimized epigenetic inhibitors for further testing and optimisation as drug candidates against the four parasites studied.

Field of science

  • /medical and health sciences/health sciences/infectious disease/malaria
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/enzymes

Call for proposal

FP7-HEALTH-2013-INNOVATION-1
See other projects for this call

Funding Scheme

CP-FP - Small or medium-scale focused research project

Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Address
Rue De Tolbiac 101
75654 Paris
France
Activity type
Research Organisations
EU contribution
€ 755 604
Administrative Contact
Virginie Chameroy (Mrs.)

Participants (15)

CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE
France
EU contribution
€ 440 840
Address
Rue Laurent Fries 1
67404 Illkirch Graffenstaden
Activity type
Research Organisations
Administrative Contact
Steve Brooks (Dr.)
MARTIN-LUTHER-UNIVERSITAET HALLE-WITTENBERG
Germany
EU contribution
€ 229 800
Address
Universitaetsplatz 10
6108 Halle (Saale)
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Sigrid Köhne (Dr.)
UNIVERSIDADE FEDERAL DO RIO DE JANEIRO
Brazil
EU contribution
€ 285 474
Address
Av Brigadeiro Trompowski Sn 2
21941 590 Rio De Janeiro
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Marcello Fantappie (Prof.)
UNIVERSIDADE DE SAO PAULO
Brazil
EU contribution
€ 411 665
Address
Rua Da Reitoria 109 Butanta
05508 900 Sao Paulo Sp
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Kem Yoshida (Mr.)
ALBERT-LUDWIGS-UNIVERSITAET FREIBURG
Germany
EU contribution
€ 374 400
Address
Fahnenbergplatz
79098 Freiburg
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Manfred Jung (Prof.)
FUNDACAO OSWALDO CRUZ
Brazil
EU contribution
€ 866 520
Address
Avenida Brasil 4365
21040 900 Rio De Janeiro
Activity type
Research Organisations
Administrative Contact
Maurício Zuma (Mr.)
INSERM TRANSFERT SA
France
EU contribution
€ 313 190
Address
Rue Watt 7
75013 Paris
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Louis Jammayrac (Mr.)
KANCERA AB
Sweden
EU contribution
€ 952 100
Address
Banvaktsvagen 22 Karolinska Institutet Science Park
171 48 Solna
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Martin Norin (Dr.)
ADLEGO BIOMEDICAL AB
Sweden
EU contribution
€ 184 863
Address
Box 42
751 03 Uppsala
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Urban Höglund (Mr.)
GRIFFITH UNIVERSITY
Australia
Address
Kessels Road Nathan
4111 Brisbane
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Nicki Church (Mrs.)
THE UNIVERSITY OF QUEENSLAND
Australia
Address
St Lucia
4072 Brisbane
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Lyn Fairlie (Mrs.)
UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA
Italy
EU contribution
€ 284 016
Address
Piazzale Aldo Moro 5
00185 Roma
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Cinzia Murdocca (Mrs.)
UNIVERSITY OF EAST ANGLIA
United Kingdom
EU contribution
€ 334 241
Address
Earlham Road
NR4 7TJ Norwich
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Yvonne Kirkham (Mrs.)
Universidade Federal de Viçosa
Brazil
EU contribution
€ 268 680
Address
Av. P.h. Rolfs S/n
36570-000 Viçosa
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Daniel Marçal De Queiroz (Mr.)
INSTITUT PASTEUR
France
EU contribution
€ 298 598
Address
Rue Du Docteur Roux 25-28
75724 Paris Cedex 15
Activity type
Research Organisations
Administrative Contact
Marie-Laure Rosso (Dr.)