Rayner Group | Human-parasite interactions in malaria

Rayner Group | Human-parasite interactions in malaria

Rayner Group

raynerteam.jpgSanger Institute, Genome Research Limited

Our Research and Approach

We use large-scale experimental approaches to identify and prioritise drug and vaccine targets in malaria. Focusing on the blood stages of human malaria parasite species, we combine systematic genetic modification, proteomics, cellular phenotyping, biochemistry and sequencing to understand basic biology and to advance new therapeutic targets.

We work in three main areas:

  • Large-scale experimental genetic screens. Working closely with Oliver Billker and Marcus Lee, we develop scalable genetic technologies and apply them to human, simian and rodent Plasmodium parasites to explore the unannotated half of the Plasmodium genome and prioritise drug targets.
  • Host-parasite interactions. Focusing on the invasion of red blood cells by P. falciparum parasites, an essential step for parasite survival and malaria pathogenesis, we work with Gavin Wright to identify new receptor-ligand interactions, and study them in the lab to prioritise new vaccine targets. We also seek to understand the role these interactions play in host specificity, including in the relatives of human Plasmodium parasites in African apes.
  • Partnership and capacity building. Plasmodium parasites are not model organisms, and all malaria research is rooted in the challenges facing endemic countries. We work closely with partners in Kenya, Ghana, India and Colombia to ensure the tools we develop are accessible to all malaria researchers.
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Dr Julian C Rayner
Group Leader

My research seeks to understand the interactions between Plasmodium parasites and human cells, in order to identify and prioritise new drug and vaccine targets. I focus on the stage of the parasite life cycle that infects human red blood cells, as it is this stage that causes all the symptoms and pathology of malaria.

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Key Projects, Collaborations, Tools & Data

Programmes, Associate Research Programmes and Facilities

Partners and Funders

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  • A novel multiple-stage antimalarial agent that inhibits protein synthesis.

    Baragaña B, Hallyburton I, Lee MC, Norcross NR, Grimaldi R et al.

    Nature 2015;522;7556;315-20

  • A genome-scale vector resource enables high-throughput reverse genetic screening in a malaria parasite.

    Gomes AR, Bushell E, Schwach F, Girling G, Anar B et al.

    Cell host & microbe 2015;17;3;404-413

  • Analysis of protein palmitoylation reveals a pervasive role in Plasmodium development and pathogenesis.

    Jones ML, Collins MO, Goulding D, Choudhary JS and Rayner JC

    Cell host & microbe 2012;12;2;246-58

  • Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum.

    Crosnier C, Bustamante LY, Bartholdson SJ, Bei AK, Theron M et al.

    Nature 2011;480;7378;534-7

  • A scalable pipeline for highly effective genetic modification of a malaria parasite.

    Pfander C, Anar B, Schwach F, Otto TD, Brochet M et al.

    Nature methods 2011;8;12;1078-82

  • Origin of the human malaria parasite Plasmodium falciparum in gorillas.

    Liu W, Li Y, Learn GH, Rudicell RS, Robertson JD et al.

    Nature 2010;467;7314;420-5

  • Adaptation of Plasmodium falciparum to humans involved the loss of an ape-specific erythrocyte invasion ligand.

    Proto WR, Siegel SV, Dankwa S, Liu W, Kemp A et al.

    Nature communications 2019;10;1;4512

  • Frequent expansion of Plasmodium vivax Duffy Binding Protein in Ethiopia and its epidemiological significance.

    Lo E, Hostetler JB, Yewhalaw D, Pearson RD, Hamid MMA et al.

    PLoS neglected tropical diseases 2019;13;9;e0007222

  • The Malaria Cell Atlas: Single parasite transcriptomes across the complete Plasmodium life cycle.

    Howick VM, Russell AJC, Andrews T, Heaton H, Reid AJ et al.

    Science (New York, N.Y.) 2019;365;6455

  • Landscape of the Plasmodium Interactome Reveals Both Conserved and Species-Specific Functionality.

    Hillier C, Pardo M, Yu L, Bushell E, Sanderson T et al.

    Cell reports 2019;28;6;1635-1647.e5

  • Plasmodium knowlesi as a model system for characterising Plasmodium vivax drug resistance candidate genes.

    Verzier LH, Coyle R, Singh S, Sanderson T and Rayner JC

    PLoS neglected tropical diseases 2019;13;6;e0007470

  • Schizont transcriptome variation among clinical isolates and laboratory-adapted clones of the malaria parasite Plasmodium falciparum.

    Tarr SJ, Díaz-Ingelmo O, Stewart LB, Hocking SE, Murray L et al.

    BMC genomics 2018;19;1;894

  • A forward genetic screen reveals a primary role for Plasmodium falciparum Reticulocyte Binding Protein Homologue 2a and 2b in determining alternative erythrocyte invasion pathways.

    Campino S, Marin-Menendez A, Kemp A, Cross N, Drought L et al.

    PLoS pathogens 2018;14;11;e1007436

  • Gimpute: An efficient genetic data imputation pipeline.

    Chen J, Lippold D, Frank J, Rayner W, Meyer-Lindenberg A and Schwarz E

    Bioinformatics (Oxford, England) 2018

  • Evolutionary history of human Plasmodium vivax revealed by genome-wide analyses of related ape parasites.

    Loy DE, Plenderleith LJ, Sundararaman SA, Liu W, Gruszczyk J et al.

    Proceedings of the National Academy of Sciences of the United States of America 2018

  • Malaria Vaccines: Recent Advances and New Horizons.

    Draper SJ, Sack BK, King CR, Nielsen CM, Rayner JC et al.

    Cell host & microbe 2018;24;1;43-56

  • RecQ helicases in the malaria parasite Plasmodium falciparum affect genome stability, gene expression patterns and DNA replication dynamics.

    Claessens A, Harris LM, Stanojcic S, Chappell L, Stanton A et al.

    PLoS genetics 2018;14;7;e1007490

  • Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis.

    Zhang M, Wang C, Otto TD, Oberstaller J, Liao X et al.

    Science (New York, N.Y.) 2018;360;6388

  • KILchip v1.0: A Novel Plasmodium falciparum Merozoite Protein Microarray to Facilitate Malaria Vaccine Candidate Prioritization.

    Kamuyu G, Tuju J, Kimathi R, Mwai K, Mburu J et al.

    Frontiers in immunology 2018;9;2866

  • Profiling invasive Plasmodium falciparum merozoites using an integrated omics approach.

    Kumar K, Srinivasan P, Nold MJ, Moch JK, Reiter K et al.

    Scientific reports 2017;7;1;17146

  • Synergistic malaria vaccine combinations identified by systematic antigen screening.

    Bustamante LY, Powell GT, Lin YC, Macklin MD, Cross N et al.

    Proceedings of the National Academy of Sciences of the United States of America 2017;114;45;12045-12050

  • Identification of highly-protective combinations of Plasmodium vivax recombinant proteins for vaccine development.

    França CT, White MT, He WQ, Hostetler JB, Brewster J et al.

    eLife 2017;6

  • Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes.

    Bushell E, Gomes AR, Sanderson T, Anar B, Girling G et al.

    Cell 2017;170;2;260-272.e8

  • Asymptomatic Plasmodium vivax infections induce robust IgG responses to multiple blood-stage proteins in a low-transmission region of western Thailand.

    Longley RJ, França CT, White MT, Kumpitak C, Sa-Angchai P et al.

    Malaria journal 2017;16;1;178

  • Extreme mutation bias and high AT content in Plasmodium falciparum.

    Hamilton WL, Claessens A, Otto TD, Kekre M, Fairhurst RM et al.

    Nucleic acids research 2017;45;4;1889-1901

  • P113 is a merozoite surface protein that binds the N terminus of Plasmodium falciparum RH5.

    Galaway F, Drought LG, Fala M, Cross N, Kemp AC et al.

    Nature communications 2017;8;14333

  • Proteomic analysis of extracellular vesicles from a Plasmodium falciparum Kenyan clinical isolate defines a core parasite secretome.

    Abdi A, Yu L, Goulding D, Rono MK, Bejon P et al.

    Wellcome open research 2017;2;50

  • Plasmodium vivax vaccine research - we've only just begun.

    Tham WH, Beeson JG and Rayner JC

    International journal for parasitology 2016

  • Study of Plasmodium falciparum DHHC palmitoyl transferases identifies a role for PfDHHC9 in gametocytogenesis.

    Tay CL, Jones ML, Hodson N, Theron M, Choudhary JS and Rayner JC

    Cellular microbiology 2016;18;11;1596-1610

  • Independent Origin and Global Distribution of Distinct Plasmodium vivax Duffy Binding Protein Gene Duplications.

    Hostetler JB, Lo E, Kanjee U, Amaratunga C, Suon S et al.

    PLoS neglected tropical diseases 2016;10;10;e0005091

  • Indels, structural variation, and recombination drive genomic diversity in Plasmodium falciparum.

    Miles A, Iqbal Z, Vauterin P, Pearson R, Campino S et al.

    Genome research 2016;26;9;1288-99

  • Genomic analysis of local variation and recent evolution in Plasmodium vivax.

    Pearson RD, Amato R, Auburn S, Miotto O, Almagro-Garcia J et al.

    Nature genetics 2016;48;8;959-964

  • Binding of Plasmodium falciparum Merozoite Surface Proteins DBLMSP and DBLMSP2 to Human Immunoglobulin M Is Conserved among Broadly Diverged Sequence Variants.

    Crosnier C, Iqbal Z, Knuepfer E, Maciuca S, Perrin AJ et al.

    The Journal of biological chemistry 2016;291;27;14285-99

  • Quantitative insertion-site sequencing (QIseq) for high throughput phenotyping of transposon mutants.

    Bronner IF, Otto TD, Zhang M, Udenze K, Wang C et al.

    Genome research 2016;26;7;980-9

  • Multigenomic Delineation of Plasmodium Species of the Laverania Subgenus Infecting Wild-living Chimpanzees and Gorillas.

    Liu W, Sundararaman SA, Loy DE, Learn GH, Li Y et al.

    Genome biology and evolution 2016

  • An Antibody Screen of a Plasmodium vivax Antigen Library Identifies Novel Merozoite Proteins Associated with Clinical Protection.

    França CT, Hostetler JB, Sharma S, White MT, Lin E et al.

    PLoS neglected tropical diseases 2016;10;5;e0004639

  • Palmitoyl Transferases have Critical Roles in the Development of Mosquito and Liver Stages of Plasmodium.

    Hopp CS, Balaban AE, Bushell E, Billker O, Rayner JC and Sinnis P

    Cellular microbiology 2016

  • Malaria Vaccine Development: Focusing Field Erythrocyte Invasion Studies on Phenotypic Diversity: The West African Merozoite Invasion Network (WAMIN).

    WAMIN Consortium Authors, Ahouidi AD, Amambua-Ngwa A, Awandare GA, Bei AK et al.

    Trends in parasitology 2016;32;4;274-83

  • Genomes of cryptic chimpanzee Plasmodium species reveal key evolutionary events leading to human malaria.

    Sundararaman SA, Plenderleith LJ, Liu W, Loy DE, Learn GH et al.

    Nature communications 2016;7;11078

  • Genomic epidemiology of artemisinin resistant malaria.

    MalariaGEN Plasmodium falciparum Community Project

    eLife 2016;5

  • A Stem Cell Strategy Identifies Glycophorin C as a Major Erythrocyte Receptor for the Rodent Malaria Parasite Plasmodium berghei.

    Yiangou L, Montandon R, Modrzynska K, Rosen B, Bushell W et al.

    PloS one 2016;11;6;e0158238

  • A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions.

    Hostetler JB, Sharma S, Bartholdson SJ, Wright GJ, Fairhurst RM and Rayner JC

    PLoS neglected tropical diseases 2015;9;12;e0004264

  • Ape parasite origins of human malaria virulence genes.

    Larremore DB, Sundararaman SA, Liu W, Proto WR, Clauset A et al.

    Nature communications 2015;6;8368

  • Plasmodium malariae Malaria: From Monkey to Man?

    Rayner JC

    EBioMedicine 2015;2;9;1023-4

  • Calcium Builds Strong Host-Parasite Interactions.

    Billker O and Rayner JC

    Cell host & microbe 2015;18;1;9-10

  • A novel multiple-stage antimalarial agent that inhibits protein synthesis.

    Baragaña B, Hallyburton I, Lee MC, Norcross NR, Grimaldi R et al.

    Nature 2015;522;7556;315-20

  • Palmitoylation and palmitoyl-transferases in Plasmodium parasites.

    Hodson N, Invergo B, Rayner JC and Choudhary JS

    Biochemical Society transactions 2015;43;2;240-5

  • A genome-scale vector resource enables high-throughput reverse genetic screening in a malaria parasite.

    Gomes AR, Bushell E, Schwach F, Girling G, Anar B et al.

    Cell host & microbe 2015;17;3;404-413

  • Post-translational protein modifications in malaria parasites.

    Doerig C, Rayner JC, Scherf A and Tobin AB

    Nature reviews. Microbiology 2015;13;3;160-72

  • The origins of malaria: there are more things in heaven and earth ….

    Keeling PJ and Rayner JC

    Parasitology 2015;142 Suppl 1;S16-25

  • Revealing the sequence and resulting cellular morphology of receptor-ligand interactions during Plasmodium falciparum invasion of erythrocytes.

    Weiss GE, Gilson PR, Taechalertpaisarn T, Tham WH, de Jong NW et al.

    PLoS pathogens 2015;11;2;e1004670

  • Plasmodium knowlesi genome sequences from clinical isolates reveal extensive genomic dimorphism.

    Pinheiro MM, Ahmed MA, Millar SB, Sanderson T, Otto TD et al.

    PloS one 2015;10;4;e0121303

  • PlasmoGEM, a database supporting a community resource for large-scale experimental genetics in malaria parasites.

    Schwach F, Bushell E, Gomes AR, Anar B, Girling G et al.

    Nucleic acids research 2015;43;Database issue;D1176-82

  • Generation of antigenic diversity in Plasmodium falciparum by structured rearrangement of Var genes during mitosis.

    Claessens A, Hamilton WL, Kekre M, Otto TD, Faizullabhoy A et al.

    PLoS genetics 2014;10;12;e1004812

  • Genome sequencing of chimpanzee malaria parasites reveals possible pathways of adaptation to human hosts.

    Otto TD, Rayner JC, Böhme U, Pain A, Spottiswoode N et al.

    Nature communications 2014;5;4754

  • Quantitation of malaria parasite-erythrocyte cell-cell interactions using optical tweezers.

    Crick AJ, Theron M, Tiffert T, Lew VL, Cicuta P and Rayner JC

    Biophysical journal 2014;107;4;846-53

  • New antigens for a multicomponent blood-stage malaria vaccine.

    Osier FH, Mackinnon MJ, Crosnier C, Fegan G, Kamuyu G et al.

    Science translational medicine 2014;6;247;247ra102

  • Confident and sensitive phosphoproteomics using combinations of collision induced dissociation and electron transfer dissociation.

    Collins MO, Wright JC, Jones M, Rayner JC and Choudhary JS

    Journal of proteomics 2014;103;1-14

  • Phosphoinositide metabolism links cGMP-dependent protein kinase G to essential Ca²⁺ signals at key decision points in the life cycle of malaria parasites.

    Brochet M, Collins MO, Smith TK, Thompson E, Sebastian S et al.

    PLoS biology 2014;12;3;e1001806

  • Plasmodium falciparum erythrocyte invasion: combining function with immune evasion.

    Wright GJ and Rayner JC

    PLoS pathogens 2014;10;3;e1003943

  • African origin of the malaria parasite Plasmodium vivax.

    Liu W, Li Y, Shaw KS, Learn GH, Plenderleith LJ et al.

    Nature communications 2014;5;3346

  • Neutralization of Plasmodium falciparum merozoites by antibodies against PfRH5.

    Douglas AD, Williams AR, Knuepfer E, Illingworth JJ, Furze JM et al.

    Journal of immunology (Baltimore, Md. : 1950) 2014;192;1;245-58

  • RH5-Basigin interaction plays a major role in the host tropism of Plasmodium falciparum.

    Wanaguru M, Liu W, Hahn BH, Rayner JC and Wright GJ

    Proceedings of the National Academy of Sciences of the United States of America 2013;110;51;20735-40

  • A library of functional recombinant cell-surface and secreted P. falciparum merozoite proteins.

    Crosnier C, Wanaguru M, McDade B, Osier FH, Marsh K et al.

    Molecular & cellular proteomics : MCP 2013;12;12;3976-86

  • Biochemical analysis of the Plasmodium falciparum erythrocyte-binding antigen-175 (EBA175)-glycophorin-A interaction: implications for vaccine design.

    Wanaguru M, Crosnier C, Johnson S, Rayner JC and Wright GJ

    The Journal of biological chemistry 2013;288;45;32106-17

  • Atypical mitogen-activated protein kinase phosphatase implicated in regulating transition from pre-S-Phase asexual intraerythrocytic development of Plasmodium falciparum.

    Balu B, Campbell C, Sedillo J, Maher S, Singh N et al.

    Eukaryotic cell 2013;12;9;1171-8

  • Global analysis of apicomplexan protein S-acyl transferases reveals an enzyme essential for invasion.

    Frénal K, Tay CL, Mueller C, Bushell ES, Jia Y et al.

    Traffic (Copenhagen, Denmark) 2013;14;8;895-911

  • Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia.

    Miotto O, Almagro-Garcia J, Manske M, Macinnis B, Campino S et al.

    Nature genetics 2013;45;6;648-55

  • Plasmodium falciparum-like parasites infecting wild apes in southern Cameroon do not represent a recurrent source of human malaria.

    Sundararaman SA, Liu W, Keele BF, Learn GH, Bittinger K et al.

    Proceedings of the National Academy of Sciences of the United States of America 2013;110;17;7020-5

  • A full-length recombinant Plasmodium falciparum PfRH5 protein induces inhibitory antibodies that are effective across common PfRH5 genetic variants.

    Bustamante LY, Bartholdson SJ, Crosnier C, Campos MG, Wanaguru M et al.

    Vaccine 2013;31;2;373-9

  • A member of the Plasmodium falciparum PHIST family binds to the erythrocyte cytoskeleton component band 4.1.

    Parish LA, Mai DW, Jones ML, Kitson EL and Rayner JC

    Malaria journal 2013;12;160

  • Recombination-mediated genetic engineering of Plasmodium berghei DNA.

    Pfander C, Anar B, Brochet M, Rayner JC and Billker O

    Methods in molecular biology (Clifton, N.J.) 2013;923;127-38

  • Analysis of protein palmitoylation reveals a pervasive role in Plasmodium development and pathogenesis.

    Jones ML, Collins MO, Goulding D, Choudhary JS and Rayner JC

    Cell host & microbe 2012;12;2;246-58

  • A Plasmodium calcium-dependent protein kinase controls zygote development and transmission by translationally activating repressed mRNAs.

    Sebastian S, Brochet M, Collins MO, Schwach F, Jones ML et al.

    Cell host & microbe 2012;12;1;9-19

  • Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing.

    Manske M, Miotto O, Campino S, Auburn S, Almagro-Garcia J et al.

    Nature 2012;487;7407;375-9

  • Ubiquitous Hepatocystis infections, but no evidence of Plasmodium falciparum-like malaria parasites in wild greater spot-nosed monkeys (Cercopithecus nictitans).

    Ayouba A, Mouacha F, Learn GH, Mpoudi-Ngole E, Rayner JC et al.

    International journal for parasitology 2012;42;8;709-13

  • Biochemical and functional analysis of two Plasmodium falciparum blood-stage 6-cys proteins: P12 and P41.

    Taechalertpaisarn T, Crosnier C, Bartholdson SJ, Hodder AN, Thompson J et al.

    PloS one 2012;7;7;e41937

  • Semaphorin-7A is an erythrocyte receptor for P. falciparum merozoite-specific TRAP homolog, MTRAP.

    Bartholdson SJ, Bustamante LY, Crosnier C, Johnson S, Lea S et al.

    PLoS pathogens 2012;8;11;e1003031

  • An adaptable two-color flow cytometric assay to quantitate the invasion of erythrocytes by Plasmodium falciparum parasites.

    Theron M, Hesketh RL, Subramanian S and Rayner JC

    Cytometry. Part A : the journal of the International Society for Analytical Cytology 2010;77;11;1067-74

  • Single genome amplification and direct amplicon sequencing of Plasmodium spp. DNA from ape fecal specimens.

    Liu W, Li Y, Peeters M, Rayner J, Sharp P et al.

    Protocol exchange 2010;2010

  • Origin of the human malaria parasite Plasmodium falciparum in gorillas.

    Liu W, Li Y, Learn GH, Rudicell RS, Robertson JD et al.

    Nature 2010;467;7314;420-5

  • Hypokalemic periodic paralysis associated with thyrotoxicosis, renal tubular acidosis and nephrogenic diabetes insipidus.

    Im EJ, Lee JM, Kim JH, Chang SA, Moon SD et al.

    Endocrine journal 2010;57;4;347-50

  • Effects of calcium signaling on Plasmodium falciparum erythrocyte invasion and post-translational modification of gliding-associated protein 45 (PfGAP45).

    Jones ML, Cottingham C and Rayner JC

    Molecular and biochemical parasitology 2009;168;1;55-62

  • Plasmodium falciparum erythrocyte invasion: a conserved myosin associated complex.

    Jones ML, Kitson EL and Rayner JC

    Molecular and biochemical parasitology 2006;147;1;74-84

  • Evolution of human-chimpanzee differences in malaria susceptibility: relationship to human genetic loss of N-glycolylneuraminic acid.

    Martin MJ, Rayner JC, Gagneux P, Barnwell JW and Varki A

    Proceedings of the National Academy of Sciences of the United States of America 2005;102;36;12819-24

  • A Plasmodium falciparum homologue of Plasmodium vivax reticulocyte binding protein (PvRBP1) defines a trypsin-resistant erythrocyte invasion pathway.

    Rayner JC, Vargas-Serrato E, Huber CS, Galinski MR and Barnwell JW

    The Journal of experimental medicine 2001;194;11;1571-81

  • Two Plasmodium falciparum genes express merozoite proteins that are related to Plasmodium vivax and Plasmodium yoelii adhesive proteins involved in host cell selection and invasion.

    Rayner JC, Galinski MR, Ingravallo P and Barnwell JW

    Proceedings of the National Academy of Sciences of the United States of America 2000;97;17;9648-53