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skILL SIGNED

Intracellular signalling by modified lipopolysaccharide

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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Project "skILL" data sheet

The following table provides information about the project.

Coordinator
MINISTERIE VAN VOLKSGEZONDHEID, WELZIJN EN SPORT 

Organization address
address: PARNASSUSPLEIN 5
city: DEN HAAG
postcode: 2500 EJ
website: n.a.

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Netherlands [NL]
 Total cost 177˙598 €
 EC max contribution 177˙598 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2017
 Funding Scheme MSCA-IF-EF-SE
 Starting year 2019
 Duration (year-month-day) from 2019-04-25   to  2021-04-24

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MINISTERIE VAN VOLKSGEZONDHEID, WELZIJN EN SPORT NL (DEN HAAG) coordinator 177˙598.00

Map

 Project objective

The adjuvant potential of bacterial lipopolysaccharide (LPS) for vaccines depends on a detailed understanding of its innate immune signalling properties, in order to achieve the right balance between immunogenicity and reactogenicity. By biosynthetic engineering of meningococcal LPS, we have obtained a unique panel of mutants covering a wide range of endotoxic activity, from the maximum wildtype level to almost totally inactive. However, this is based on activation of the TLR4/MD-2 receptor, and recent studies have revealed that LPS endotoxic activity is also mediated by the intracellular receptor caspase 4 (caspase 11 in the mouse). At present, it is not clear how this contributes to the overall biological activity of LPS, and how it can be modified by structural alterations to the lipid A moiety of LPS. A major contribution of the proposed project will be to provide for the first time a detailed structure-function relationship for this LPS-caspase 4/11 interaction. This information will be crucial in the further evaluation of the adjuvant potential of these LPS derivatives, as well as giving more insight in the role of LPS modification in the interaction of pathogenic bacteria with the innate immune system. LPS mutants with differential effects on the TLR4 and caspase pathways will provide a unique opportunity to tease apart the contributions of both pathways to the overall LPS biological activity. In addition, we will explore the role of delivery of LPS by OMVs (outer membrane vesicles) to the intracellular pathway activation. A second and complementary contribution will be the development of novel LPS purification methods, which will also lead to better understanding of LPS structure-function relationships by allowing the separation of complicated LPS mixtures in their individual molecular species. In addition, they will pave the way for purification procedures which can be upscaled for making clinical grade LPS in human vaccine applications.

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The information about "SKILL" are provided by the European Opendata Portal: CORDIS opendata.

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