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Molecular basis of the outer membrane permeability

Objective

Overcoming the barriers that the cell envelope and efflux pumps provide to Gram-negative bacteria is a major bottleneck in the discovery and development of new antibiotics. To respond to this Call we are extending our current network on antibiotic translocation and propose an ambitious project ranging from identification of novel resistance mechanisms in clinical bacterial isolates to crystallization of molecular resistance components and all-atom modeling to determine the kinetics of permeation. Our particular strength lies in the identification and quantification of transport proteins involved in membrane permeation at the cellular level combined with our expertise in quantifying the rate limiting steps of translocation at atomic level. Based on our experience we intend to:

1. develop multiple assays to determine intracellular concentrations of small molecules
2. increase the overall structural knowledge of outer membrane proteins
3. extend knowledge on active-uptake transport systems, such as iron transport
4. identify novel targets whose modulation can alter the penetration of other small molecules
5. obtain as complete a picture as possible of small molecule penetration into and efflux out of bacterial cells

Combining the research question at different levels we expect to understand the complexity of membrane permeability. In particular, we are convinced that our molecular approach is able to provide a general template for a guided design of antibiotics to achieve high permeability.

In addition, we will create a data base to allow the sharing of antibacterial R&D information on an unprecedented level. Also, via careful analysis of this information we intend to provide learnings as best practices that will lead to an increase in the overall efficiency of antibacterial R&D.

Call for proposal

IMI-JU-06-2012
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Coordinator

GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT LTD.
Address
Great West Road 980
TW89GS Brentford
United Kingdom

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Principal investigator
Robert Stavenger (Dr)
Administrative Contact
Miles Sally (-)

Participants (27)

JACOBS UNIVERSITY BREMEN GGMBH
Germany
EU contribution
€ 4 178 960
Address
Campus Ring 1
28725 Bremen

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Ronald Kieschnick (Mr.)
UNIVERSITA DEGLI STUDI DI CAGLIARI
Italy
EU contribution
€ 1 678 960
Address
Via Universita 40
09124 Cagliari

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Luciano Colombo (Prof.)
THE UNIVERSITY COURT OF THE UNIVERSITY OF ST ANDREWS
United Kingdom
EU contribution
€ 886 152
Address
North Street 66 College Gate
KY16 9AJ St Andrews

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Trish Starrs (Ms)
JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN
Germany
EU contribution
€ 499 000
Address
Theodor W Adorno Platz 1
60323 Frankfurt Am Main

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Kristina Wege (Ms)
UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN
Ireland
EU contribution
€ 90 313
Address
Belfield
4 Dublin

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Donal Doolan (Mr)
NANION TECHNOLOGIES GMBH
Germany
EU contribution
€ 293 200
Address
Ganghoferstrasse 70a
80339 Munchen

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Niels Fertig (Dr.)
BRUKER DALTONIK GMBH
Germany
Address
Fahrenheitstrasse 4
28359 Bremen

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Tanja Hohnhorst (Ms.)
FUNDACION PRIVADA INSTITUTO DE SALUD GLOBAL BARCELONA
Spain
EU contribution
€ 203 639
Address
C Rossello
08036 Barcelona

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Administrative Contact
Jordi Vila (Dr.)
IONOVATION GMBH
Germany
EU contribution
€ 450 400
Address
Westerbreite 7
49084 Osnabruck

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Karsten Gall (Dr.)
UNIVERSITY OF NEWCASTLE UPON TYNE
United Kingdom
EU contribution
€ 894 625
Address
Kings Gate
NE1 7RU Newcastle Upon Tyne

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Amanda Gregory (Dr.)
UNIVERSITAETSKLINIKUM FREIBURG
Germany
EU contribution
€ 299 351
Address
Hugstetter Strasse 49
79106 Freiburg

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Katharina Strub (Ms.)
UNIVERSITE DE GENEVE
Switzerland
EU contribution
€ 937 537
Address
Rue Du General Dufour 24
1211 Geneve

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Christian Van Delden (Prof.)
UNIVERSITAT BASEL
Switzerland
EU contribution
€ 1 221 131
Address
Petersplatz 1
4051 Basel

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Rachel Benzies (Dr.)
European ScreeningPort GmbH

Participation ended

Germany
EU contribution
€ 232 618
Address
Schnackenburgallee
22525 Hamburg

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Mira Grättinger (Dr.)
Nanospot GmbH

Participation ended

Germany
EU contribution
€ 57 284
Address
Johann-krane-weg
48149 Münster

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Administrative Contact
Sebastian Giehring (Dr)
SYNCHROTRON SOLEIL SOCIETE CIVILE
France
EU contribution
€ 304 000
Address
L Orme Des Merisiers
91190 Saint Aubin

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Yves Le Ray (Mr)
ASSISTANCE PUBLIQUE HOPITAUX DE PARIS
France
EU contribution
€ 103 931
Address
3 Avenue Victoria
75000 Paris

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Activity type
Research Organisations
Administrative Contact
Alix Pillot (Ms)
Yelen
France
EU contribution
€ 110 263
Address
Boulevard Tempête
13820 Ensues La Redonne

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Administrative Contact
Nicolas VIDAL (Engineer)
UNIVERSITE D'AIX MARSEILLE
France
EU contribution
€ 1 653 621
Address
Boulevard Charles Livon 58 Le Pharo
13284 Marseille

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Celine Damon (Ms)
SANOFI-AVENTIS RECHERCHE & DEVELOPPEMENT
France
Address
Pierre Brossolette 1
91380 Chilly Mazarin

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Nathalia Murillo (Dr.)
ASTRAZENECA AB
Sweden
Address
Vastra Maelarhamnen
151 85 Sodertaelje

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Eva Lindgren (Senior Director)
BASILEA PHARMACEUTICA INTERNATIONAL AG
Switzerland
Address
Grenzacherstrasse 487
4058 Basel

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Laurenz Kellenberger (Dr)
JANSSEN PHARMACEUTICA NV
Belgium
Address
Turnhoutseweg 30
2340 Beerse

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Kristien Bonroy (Ms)
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France
EU contribution
€ 540 600
Address
Rue Michel Ange 3
75794 Paris

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Activity type
Research Organisations
Administrative Contact
Gaëlle BUJAN (Ms.)
THE HYVE BV
Netherlands
EU contribution
€ 326 064
Address
Arthur Van Schendelstraat 650
3511 MJ Utrecht

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Kees Van Bochove (Msc.)
GRITSYSTEMS AS
Denmark
EU contribution
€ 349 875
Address
Trekronergade 126f, 3 Tv
2500 Valby

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Claus Stie Kallesøe (Mr)
FRAUNHOFER GESELLSCHAFT ZUR FORDERUNG DER ANGEWANDTEN FORSCHUNG EV
Germany
EU contribution
€ 672 679
Address
Hansastrasse 27c
80686 Munchen

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Activity type
Research Organisations
Administrative Contact
Michael Prestele (Mr)