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BoneMalar SIGNED

Mechanisms of bone marrow sequestration during malaria infection

Total Cost €

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EC-Contrib. €

0

Partnership

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 BoneMalar project word cloud

Explore the words cloud of the BoneMalar project. It provides you a very rough idea of what is the project "BoneMalar" about.

vascular    plasmodium    cycle    biology    preliminary    pathogen    recognition    therapies    parasites    circulation    human    multifaceted    initiate    marrow    spleen    tissues    bone    compelling    interaction    cell    paradigm    stages    release    virulence    countries    avenue    infection    series    asexual    sub    sequester    red    malaria    children    parasite    caused    strategies    vasculature    intervention    adhere    deep    infected    deadly    completion    model    confirmed    body    predominantly    africa    environment    led    mosquito    saharan    endothelium    existence    capability    replicating    cells    public    characterization    transmigrate    interface    suggest    pathogenesis    gametocytes    treatments    interactions    adherence    home    stage    vector    demonstrated    critical    600000    health    questions    multidiscipinary    host    sequestration    reservoir    resistance    clearance    blood    mouse    multiple    responsible    deaths    surveillance    urgent    life    transmission    extravascular    innovative    falciparum    macrophages    asexually   

Project "BoneMalar" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITY OF GLASGOW 

Organization address
address: UNIVERSITY AVENUE
city: GLASGOW
postcode: G12 8QQ
website: www.gla.ac.uk

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 United Kingdom [UK]
 Project website https://www.gla.ac.uk/researchinstitutes/iii/staff/matthiasmarti/
 Total cost 2˙298˙557 €
 EC max contribution 2˙298˙557 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-06-01   to  2021-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITY OF GLASGOW UK (GLASGOW) coordinator 2˙298˙557.00

Map

 Project objective

Malaria remains a major problem of public health in developing countries. It is responsible for about 600000 deaths per year, predominantly children in sub-Saharan Africa. There is an urgent need for novel therapies as resistance against current treatments is widespread. The complex parasite biology requires a multifaceted approach targeting multiple life cycle stages and virulence pathways. The pathogenesis of the most deadly of human malaria parasites, Plasmodium falciparum, is related to the capability of infected red blood cells to sequester in deep tissues. Sequestration is critical for the completion of the red blood cell cycle because the release of parasites into the blood circulation allows recognition by surveillance macrophages and clearance in the spleen. A series of studies have since led to the understanding that sequestration of asexually replicating parasites is caused by the adherence of parasite infected red blood cells to the vascular endothelium of various tissues in the body. We have recently demonstrated that gametocytes, the only stage capable of transmission to the mosquito vector, develop in the extravascular environment of the human bone marrow. Preliminary studies in the mouse model have confirmed this finding and also suggest existence of an asexual reservoir in the bone marrow. In this innovative multidiscipinary proposal we aim to investigate the host pathogen interactions at the interface between infected red blood cell and bone marrow vasculature. Specifically we will focus on the following questions: how do parasites home to bone marrow? What are the changes in the bone marrow endothelium upon infection? How do parasites adhere with and transmigrate across the vascular endothelium in the bone marrow? The proposed studies initiate detailed characterization of a new paradigm in malaria parasite interaction with the host vasculature and provide a compelling new avenue for intervention strategies.

 Publications

year authors and title journal last update
List of publications.
2019 Kathleen W. Dantzler, Siyuan Ma, Priscilla Ngotho, Will J. R. Stone, Dingyin Tao, Sanna Rijpma, Mariana De Niz, Sandra K. Nilsson Bark, Matthijs M. Jore, Tonke K. Raaijmakers, Angela M. Early, Ceereena Ubaida-Mohien, Leandro Lemgruber, Joseph J. Campo, Andy A. Teng, Timothy Q. Le, Cassidy L. Walker, Patricia Hermand, Philippe Deterre, D. Huw Davies, Phil Felgner, Isabelle Morlais, Dyann F. Wirth,
Naturally acquired immunity against immature Plasmodium falciparum gametocytes
published pages: eaav3963, ISSN: 1946-6234, DOI: 10.1126/scitranslmed.aav3963
Science Translational Medicine 11/495 2019-08-30
2019 Priscilla Ngotho, Alexandra Blancke Soares, Franziska Hentzschel, Fiona Achcar, Lucia Bertuccini, Matthias Marti
Revisiting gametocyte biology in malaria parasites
published pages: 401-414, ISSN: 1574-6976, DOI: 10.1093/femsre/fuz010
FEMS Microbiology Reviews 43/4 2019-08-29
2018 Mariana De Niz, Elamaran Meibalan, Pedro Mejia, Siyuan Ma, Nicolas M. B. Brancucci, Carolina Agop-Nersesian, Rebecca Mandt, Priscilla Ngotho, Katie R. Hughes, Andrew P. Waters, Curtis Huttenhower, James R. Mitchell, Roberta Martinelli, Friedrich Frischknecht, Karl B. Seydel, Terrie Taylor, Danny Milner, Volker T. Heussler, Matthias Marti
Plasmodium gametocytes display homing and vascular transmigration in the host bone marrow
published pages: eaat3775, ISSN: 2375-2548, DOI: 10.1126/sciadv.aat3775
Science Advances 4/5 2019-05-10
2017 Pedro Mejia, J. Humberto Treviño-Villarreal, Justin S. Reynolds, Mariana De Niz, Andrew Thompson, Matthias Marti, James R. Mitchell
A single rapamycin dose protects against late-stage experimental cerebral malaria via modulation of host immunity, endothelial activation and parasite sequestration
published pages: , ISSN: 1475-2875, DOI: 10.1186/s12936-017-2092-5
Malaria Journal 16/1 2019-05-10

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