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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.

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

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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