Rapid identification of genes controlling virulence and immunity in malaria parasites

Handle URI:
http://hdl.handle.net/10754/625229
Title:
Rapid identification of genes controlling virulence and immunity in malaria parasites
Authors:
Abkallo, Hussein M.; Martinelli, Axel ( 0000-0003-2662-7162 ) ; Inoue, Megumi ( 0000-0002-6595-8282 ) ; Ramaprasad, Abhinay ( 0000-0001-9372-5526 ) ; Xangsayarath, Phonepadith; Gitaka, Jesse ( 0000-0001-7516-522X ) ; Tang, Jianxia; Yahata, Kazuhide; Zoungrana, Augustin; Mitaka, Hayato; Acharjee, Arita; Datta, Partha P.; Hunt, Paul; Carter, Richard; Kaneko, Osamu; Mustonen, Ville; Illingworth, Christopher J. R. ( 0000-0002-0030-2784 ) ; Pain, Arnab ( 0000-0002-1755-2819 ) ; Culleton, Richard ( 0000-0001-8808-5771 )
Abstract:
Identifying the genetic determinants of phenotypes that impact disease severity is of fundamental importance for the design of new interventions against malaria. Here we present a rapid genome-wide approach capable of identifying multiple genetic drivers of medically relevant phenotypes within malaria parasites via a single experiment at single gene or allele resolution. In a proof of principle study, we found that a previously undescribed single nucleotide polymorphism in the binding domain of the erythrocyte binding like protein (EBL) conferred a dramatic change in red blood cell invasion in mutant rodent malaria parasites Plasmodium yoelii. In the same experiment, we implicated merozoite surface protein 1 (MSP1) and other polymorphic proteins, as the major targets of strain-specific immunity. Using allelic replacement, we provide functional validation of the substitution in the EBL gene controlling the growth rate in the blood stages of the parasites.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
Abkallo HM, Martinelli A, Inoue M, Ramaprasad A, Xangsayarath P, et al. (2017) Rapid identification of genes controlling virulence and immunity in malaria parasites. PLOS Pathogens 13: e1006447. Available: http://dx.doi.org/10.1371/journal.ppat.1006447.
Publisher:
Public Library of Science (PLoS)
Journal:
PLOS Pathogens
KAUST Grant Number:
BAS/1/1020-01-01
Issue Date:
13-Jul-2017
DOI:
10.1371/journal.ppat.1006447
Type:
Article
ISSN:
1553-7374
Sponsors:
This work was supported by the JSPS (project numbers Nos. JP25870525, JP24255009 and JP16K21233) (to RCu), A Royal Society Bilateral Grant for Co-operative Research (to RCa and RCu) and a Sasakawa Foundation Butterfield Award (to RCu), faculty baseline fund (BAS/1/1020-01-01) from the King Abdullah University of Science and Technology (KAUST) to AP, and Grants-in-Aid for Scientific Research on Innovative Areas JR23117008 (to OK). CJRI was supported by a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (101239/Z/13/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Additional Links:
http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006447
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorAbkallo, Hussein M.en
dc.contributor.authorMartinelli, Axelen
dc.contributor.authorInoue, Megumien
dc.contributor.authorRamaprasad, Abhinayen
dc.contributor.authorXangsayarath, Phonepadithen
dc.contributor.authorGitaka, Jesseen
dc.contributor.authorTang, Jianxiaen
dc.contributor.authorYahata, Kazuhideen
dc.contributor.authorZoungrana, Augustinen
dc.contributor.authorMitaka, Hayatoen
dc.contributor.authorAcharjee, Aritaen
dc.contributor.authorDatta, Partha P.en
dc.contributor.authorHunt, Paulen
dc.contributor.authorCarter, Richarden
dc.contributor.authorKaneko, Osamuen
dc.contributor.authorMustonen, Villeen
dc.contributor.authorIllingworth, Christopher J. R.en
dc.contributor.authorPain, Arnaben
dc.contributor.authorCulleton, Richarden
dc.date.accessioned2017-07-19T10:45:03Z-
dc.date.available2017-07-19T10:45:03Z-
dc.date.issued2017-07-13en
dc.identifier.citationAbkallo HM, Martinelli A, Inoue M, Ramaprasad A, Xangsayarath P, et al. (2017) Rapid identification of genes controlling virulence and immunity in malaria parasites. PLOS Pathogens 13: e1006447. Available: http://dx.doi.org/10.1371/journal.ppat.1006447.en
dc.identifier.issn1553-7374en
dc.identifier.doi10.1371/journal.ppat.1006447en
dc.identifier.urihttp://hdl.handle.net/10754/625229-
dc.description.abstractIdentifying the genetic determinants of phenotypes that impact disease severity is of fundamental importance for the design of new interventions against malaria. Here we present a rapid genome-wide approach capable of identifying multiple genetic drivers of medically relevant phenotypes within malaria parasites via a single experiment at single gene or allele resolution. In a proof of principle study, we found that a previously undescribed single nucleotide polymorphism in the binding domain of the erythrocyte binding like protein (EBL) conferred a dramatic change in red blood cell invasion in mutant rodent malaria parasites Plasmodium yoelii. In the same experiment, we implicated merozoite surface protein 1 (MSP1) and other polymorphic proteins, as the major targets of strain-specific immunity. Using allelic replacement, we provide functional validation of the substitution in the EBL gene controlling the growth rate in the blood stages of the parasites.en
dc.description.sponsorshipThis work was supported by the JSPS (project numbers Nos. JP25870525, JP24255009 and JP16K21233) (to RCu), A Royal Society Bilateral Grant for Co-operative Research (to RCa and RCu) and a Sasakawa Foundation Butterfield Award (to RCu), faculty baseline fund (BAS/1/1020-01-01) from the King Abdullah University of Science and Technology (KAUST) to AP, and Grants-in-Aid for Scientific Research on Innovative Areas JR23117008 (to OK). CJRI was supported by a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (101239/Z/13/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.publisherPublic Library of Science (PLoS)en
dc.relation.urlhttp://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006447en
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleRapid identification of genes controlling virulence and immunity in malaria parasitesen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalPLOS Pathogensen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionInstitute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.en
dc.contributor.institutionGraduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.en
dc.contributor.institutionDepartment of Protozooolgy, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.en
dc.contributor.institutionCentre for Malaria Elimination, School of Medicine, Mount Kenya University, Thika, Kenya.en
dc.contributor.institutionKey Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Jiangsu, China.en
dc.contributor.institutionMalaria Unit, Department of Pathology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.en
dc.contributor.institutionIndian Institute of Science Education and Research Kolkata, Mohanpur - 741 246, West Bengal, India.en
dc.contributor.institutionWellcome Trust Sanger Institute, Hinxton, United Kingdom.en
dc.contributor.institutionDepartment of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge, United Kingdom.en
kaust.authorMartinelli, Axelen
kaust.authorRamaprasad, Abhinayen
kaust.authorPain, Arnaben
kaust.grant.numberBAS/1/1020-01-01en
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