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CR-PHAGOCYTOSIS

Complement-mediated phagocytosis in neutrophils

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EC-Contrib. €

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Project "CR-PHAGOCYTOSIS" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITAIR MEDISCH CENTRUM UTRECHT 

Organization address
address: HEIDELBERGLAAN 100
city: UTRECHT
postcode: 3584 CX
website: www.umcutrecht.nl

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]
 Project website http://www.evasionutrecht.nl/themes/suzan-rooijakkers-bacteria-complement/
 Total cost 165˙598 €
 EC max contribution 165˙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-2014
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2015
 Duration (year-month-day) from 2015-04-01   to  2017-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAIR MEDISCH CENTRUM UTRECHT NL (UTRECHT) coordinator 165˙598.00

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 Project objective

Complement-mediated phagocytosis plays a crucial role in bacterial killing. Activation of complement yields a variety of opsonin molecules that can rapidly coat bacterial surfaces, which interact with complement receptors on neutrophils to facilitate phagocytosis. However the molecular details and functional outcomes of these interactions are not well understood. In the proposed work, we aim to elucidate the molecular details of complement opsonin-receptor interactions. We have developed a novel model for examining molecular complement interactions, by site-specifically attaching complement opsonins to bacteria-sized beads in their correct orientation. We will, for the first time, be able to adequately characterize complement opsonin-receptor interactions at a molecular level. This methodology will also be extended to two model gram-positive bacteria, Staphylococcus aureus (S. aureus) and Group B Streptococcus (GBS), in which complement opsonins will be site-specifically attached to their cell walls. Using wild-type and complement receptor (CR) knockdown neutrophils, we aim to determine the roles of opsonin-receptor pairs in neutrophil activation and bacterial killing. Finally, we will use our model systems to examine the synergy between antibodies and complement in neutrophil phagocytosis. The proposed work will provide a comprehensive picture of the role of complement in neutrophil phagocytosis. As the role of complement in human disease is becoming increasingly apparent, the need for new therapeutics is imminent. The work proposed herein paves the way for several therapeutic applications, including targeted complement-dependent cytotoxicity (CDC) immunotherapeutics in cancer and complement inhibitors for a wide array of age-related, autoimmune, and rare/neglected disorders.

 Publications

year authors and title journal last update
List of publications.
2016 Kirsten J. Koymans, Manouk Vrieling, Ronald D. Gorham, Jos A. G. van Strijp
Staphylococcal Immune Evasion Proteins: Structure, Function, and Host Adaptation
published pages: 1-49, ISSN: , DOI: 10.1007/82_2015_5017
Current Topics in Microbiology and Immunology 2019-07-24
2015 Evelien T. M. Berends, Ronald D. Gorham, Maartje Ruyken, Jasper A. Soppe, Hatice Orhan, Piet C. Aerts, Carla J. C. de Haas, Piet Gros, Suzan H. M. Rooijakkers
Molecular insights into the surface-specific arrangement of complement C5 convertase enzymes
published pages: , ISSN: 1741-7007, DOI: 10.1186/s12915-015-0203-8
BMC Biology 13/1 2019-07-24

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