Dr Oliver Billker | Senior Group Leader

Billker, Oliver

Oliver develops new genetic technologies to investigate how malaria parasites reproduce in mosquitoes and get transmitted.

Understanding how malaria parasites get transmitted holds one of the keys to preventing the disease from spreading.  Since transmission is closely linked with sexual reproduction, it is also at the heart of how the parasites evolve through recombining their genes. How Plasmodium species transition between host and vector and how they use cues from their hosts to time mating and reproduction has always fascinated me.

These biological questions still drive much of my work, but I also realise that answers will come more easily, the better we can engineer the parasite’s genome. Together with my colleagues, Julian Rayner and Marcus Lee, we therefore continue to invest heavily into new technologies that are beginning to reveal gene functions in malaria parasites at unprecedented scale. We are keen to share these tools and resources widely, since we realise how useful they will be to understand the disease and to find new targets for drugs and vaccines.

Having spent much of the past years designing and running a DNA engineering pipeline, we are pleased that the PlasmoGEM project has produced vectors for the deletion of almost half of all Plasmodium berghei genes. It is now easy to make large numbers of mutants, each identified through its own molecular barcode. Importantly, barcodes allow us to screen mutants for specific phenotypes and we are excited to think about all the new possibilities this creates.

To identify new gene functions we often combine mutated parasites with a very detailed analysis of all their transcripts, proteins or protein modifications. With our collaborators this has allowed us to find a master regulator of sexual development and mosquito transmission, and to define a new pathway that regulates many key events in the parasite’s life cycle.

We also like to take comparative approaches, and by collaborating with a group working on green algae we keep discovering new molecular players in fertilisation that  are so ancient that most sexually reproducing organisms are using them today. Finally, we work closely with the Cellular Genetics Programme to ask how genetically engineered stem cells can help us study pathogen host interactions more effectively.

Publications

  • 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;404-13

  • 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

  • A comprehensive evaluation of rodent malaria parasite genomes and gene expression.

    Otto TD, Böhme U, Jackson AP, Hunt M, Franke-Fayard B et al.

    BMC biology 2014;12;86

  • 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

  • A cascade of DNA-binding proteins for sexual commitment and development in Plasmodium.

    Sinha A, Hughes KR, Modrzynska KK, Otto TD, Pfander C et al.

    Nature 2014;507;7491;253-7

  • Comparative genomics in Chlamydomonas and Plasmodium identifies an ancient nuclear envelope protein family essential for sexual reproduction in protists, fungi, plants, and vertebrates.

    Ning J, Otto TD, Pfander C, Schwach F, Brochet M et al.

    Genes & development 2013;27;10;1198-215

  • A tetracycline-repressible transactivator system to study essential genes in malaria parasites.

    Pino P, Sebastian S, Kim EA, Bush E, Brochet M et al.

    Cell host & microbe 2012;12;6;824-34

  • 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

  • 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

  • The systematic functional analysis of Plasmodium protein kinases identifies essential regulators of mosquito transmission.

    Tewari R, Straschil U, Bateman A, Böhme U, Cherevach I et al.

    Cell host & microbe 2010;8;4;377-87

  • The conserved plant sterility gene HAP2 functions after attachment of fusogenic membranes in Chlamydomonas and Plasmodium gametes.

    Liu Y, Tewari R, Ning J, Blagborough AM, Garbom S et al.

    Genes & development 2008;22;8;1051-68

  • Calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in a malaria parasite.

    Billker O, Dechamps S, Tewari R, Wenig G, Franke-Fayard B and Brinkmann V

    Cell 2004;117;4;503-14

  • Distinct mechanisms of internalization of Neisseria gonorrhoeae by members of the CEACAM receptor family involving Rac1- and Cdc42-dependent and -independent pathways.

    Billker O, Popp A, Brinkmann V, Wenig G, Schneider J et al.

    The EMBO journal 2002;21;4;560-71

  • Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito.

    Billker O, Lindo V, Panico M, Etienne AE, Paxton T et al.

    Nature 1998;392;6673;289-92

  • Proteomic profiling of the brain of mice with experimental cerebral malaria.

    Moussa E, Huang H, Ahras M, Lall A, Thezenas ML et al.

    Journal of proteomics 2017

  • Single-cell RNA-seq and computational analysis using temporal mixture modelling resolves Th1/Tfh fate bifurcation in malaria.

    Lönnberg T, Svensson V, James KR, Fernandez-Ruiz D, Sebina I et al.

    Science immunology 2017;2;9

  • Decreased Rate of Plasma Arginine Appearance in Murine Malaria May Explain Hypoargininemia in Children With Cerebral Malaria.

    Alkaitis MS, Wang H, Ikeda AK, Rowley CA, MacCormick IJ et al.

    The Journal of infectious diseases 2016;214;12;1840-1849

  • Invasion of hepatocytes by Plasmodium sporozoites requires cGMP-dependent protein kinase and calcium dependent protein kinase 4.

    Govindasamy K, Jebiwott S, Jaijyan DK, Davidow A, Ojo KK et al.

    Molecular microbiology 2016

  • 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

  • Calcium signalling in malaria parasites.

    Brochet M and Billker O

    Molecular microbiology 2016

  • 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

  • Enhanced Methylation Analysis by Recovery of Unsequenceable Fragments.

    McInroy GR, Beraldi D, Raiber EA, Modrzynska K, van Delft P et al.

    PloS one 2016;11;3;e0152322

  • A comprehensive evaluation of rodent malaria parasite genomes and gene expression.

    Otto TD, Böhme U, Jackson AP, Hunt M, Franke-Fayard B et al.

    BMC biology 2014;12;86

  • BCKDH: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei.

    Oppenheim RD, Creek DJ, Macrae JI, Modrzynska KK, Pino P et al.

    PLoS pathogens 2014;10;7;e1004263

  • A cascade of DNA-binding proteins for sexual commitment and development in Plasmodium.

    Sinha A, Hughes KR, Modrzynska KK, Otto TD, Pfander C et al.

    Nature 2014;507;7491;253-7

  • 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

  • Efficacy of a Plasmodium vivax malaria vaccine using ChAd63 and modified vaccinia Ankara expressing thrombospondin-related anonymous protein as assessed with transgenic Plasmodium berghei parasites.

    Bauza K, Malinauskas T, Pfander C, Anar B, Jones EY et al.

    Infection and immunity 2014;82;3;1277-86

  • 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

  • Comparative genomics in Chlamydomonas and Plasmodium identifies an ancient nuclear envelope protein family essential for sexual reproduction in protists, fungi, plants, and vertebrates.

    Ning J, Otto TD, Pfander C, Schwach F, Brochet M et al.

    Genes & development 2013;27;10;1198-215

  • Defining the range of pathogens susceptible to Ifitm3 restriction using a knockout mouse model.

    Everitt AR, Clare S, McDonald JU, Kane L, Harcourt K et al.

    PloS one 2013;8;11;e80723

  • A tetracycline-repressible transactivator system to study essential genes in malaria parasites.

    Pino P, Sebastian S, Kim EA, Bush E, Brochet M et al.

    Cell host & microbe 2012;12;6;824-34

  • 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

  • Transmission of malaria to mosquitoes blocked by bumped kinase inhibitors.

    Ojo KK, Pfander C, Mueller NR, Burstroem C, Larson ET et al.

    The Journal of clinical investigation 2012;122;6;2301-5

  • 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

  • Genetic and transcriptional analysis of phosphoinositide-specific phospholipase C in Plasmodium.

    Raabe A, Berry L, Sollelis L, Cerdan R, Tawk L et al.

    Experimental parasitology 2011;129;1;75-80

  • Multiple roles for Plasmodium berghei phosphoinositide-specific phospholipase C in regulating gametocyte activation and differentiation.

    Raabe AC, Wengelnik K, Billker O and Vial HJ

    Cellular microbiology 2011;13;7;955-66

  • Cutting edge: the membrane attack complex of complement is required for the development of murine experimental cerebral malaria.

    Ramos TN, Darley MM, Hu X, Billker O, Rayner JC et al.

    Journal of immunology (Baltimore, Md. : 1950) 2011;186;12;6657-60

  • The systematic functional analysis of Plasmodium protein kinases identifies essential regulators of mosquito transmission.

    Tewari R, Straschil U, Bateman A, Böhme U, Cherevach I et al.

    Cell host & microbe 2010;8;4;377-87

  • A parasite calcium switch and Achilles' heel revealed.

    Doerig C and Billker O

    Nature structural & molecular biology 2010;17;5;541-3

  • Quantitative assessment of DNA replication to monitor microgametogenesis in Plasmodium berghei.

    Raabe AC, Billker O, Vial HJ and Wengelnik K

    Molecular and biochemical parasitology 2009;168;2;172-6

  • A cyclic GMP signalling module that regulates gliding motility in a malaria parasite.

    Moon RW, Taylor CJ, Bex C, Schepers R, Goulding D et al.

    PLoS pathogens 2009;5;9;e1000599

  • Signalling in malaria parasites. The MALSIG consortium.

    Doerig C, Baker D, Billker O, Blackman MJ, Chitnis C et al.

    Parasite (Paris, France) 2009;16;3;169-82

  • An essential role for the Plasmodium Nek-2 Nima-related protein kinase in the sexual development of malaria parasites.

    Reininger L, Tewari R, Fennell C, Holland Z, Goldring D et al.

    The Journal of biological chemistry 2009;284;31;20858-68

  • Calcium-dependent signaling and kinases in apicomplexan parasites.

    Billker O, Lourido S and Sibley LD

    Cell host & microbe 2009;5;6;612-22

  • Protein kinases of malaria parasites: an update.

    Doerig C, Billker O, Haystead T, Sharma P, Tobin AB and Waters NC

    Trends in parasitology 2008;24;12;570-7

  • Gametogenesis in malaria parasites is mediated by the cGMP-dependent protein kinase.

    McRobert L, Taylor CJ, Deng W, Fivelman QL, Cummings RM et al.

    PLoS biology 2008;6;6;e139

  • The conserved plant sterility gene HAP2 functions after attachment of fusogenic membranes in Chlamydomonas and Plasmodium gametes.

    Liu Y, Tewari R, Ning J, Blagborough AM, Garbom S et al.

    Genes & development 2008;22;8;1051-68

  • Heparan sulfate proteoglycans provide a signal to Plasmodium sporozoites to stop migrating and productively invade host cells.

    Coppi A, Tewari R, Bishop JR, Bennett BL, Lawrence R et al.

    Cell host & microbe 2007;2;5;316-27

  • Plasmodium berghei calcium-dependent protein kinase 3 is required for ookinete gliding motility and mosquito midgut invasion.

    Siden-Kiamos I, Ecker A, Nybäck S, Louis C, Sinden RE and Billker O

    Molecular microbiology 2006;60;6;1355-63

  • Generation of gene targeting constructs for Plasmodium berghei by a PCR-based method amenable to high throughput applications.

    Ecker A, Moon R, Sinden RE and Billker O

    Molecular and biochemical parasitology 2006;145;2;265-8

  • Protein kinases as targets for antimalarial intervention: Kinomics, structure-based design, transmission-blockade, and targeting host cell enzymes.

    Doerig C, Billker O, Pratt D and Endicott J

    Biochimica et biophysica acta 2005;1754;1-2;132-50

  • An atypical mitogen-activated protein kinase controls cytokinesis and flagellar motility during male gamete formation in a malaria parasite.

    Tewari R, Dorin D, Moon R, Doerig C and Billker O

    Molecular microbiology 2005;58;5;1253-63

  • A NIMA-related protein kinase is essential for completion of the sexual cycle of malaria parasites.

    Reininger L, Billker O, Tewari R, Mukhopadhyay A, Fennell C et al.

    The Journal of biological chemistry 2005;280;36;31957-64

  • Calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in a malaria parasite.

    Billker O, Dechamps S, Tewari R, Wenig G, Franke-Fayard B and Brinkmann V

    Cell 2004;117;4;503-14

  • Differential recognition of members of the carcinoembryonic antigen family by Afa/Dr adhesins of diffusely adhering Escherichia coli (Afa/Dr DAEC).

    Berger CN, Billker O, Meyer TF, Servin AL and Kansau I

    Molecular microbiology 2004;52;4;963-83

  • The dynamics of interactions between Plasmodium and the mosquito: a study of the infectivity of Plasmodium berghei and Plasmodium gallinaceum, and their transmission by Anopheles stephensi, Anopheles gambiae and Aedes aegypti.

    Alavi Y, Arai M, Mendoza J, Tufet-Bayona M, Sinha R et al.

    International journal for parasitology 2003;33;9;933-43

  • Azadirachtin disrupts formation of organised microtubule arrays during microgametogenesis of Plasmodium berghei.

    Billker O, Shaw MK, Jones IW, Ley SV, Mordue AJ and Sinden RE

    The Journal of eukaryotic microbiology 2002;49;6;489-97

  • Nuclear factor-kappa B directs carcinoembryonic antigen-related cellular adhesion molecule 1 receptor expression in Neisseria gonorrhoeae-infected epithelial cells.

    Muenzner P, Billker O, Meyer TF and Naumann M

    The Journal of biological chemistry 2002;277;9;7438-46

  • Distinct mechanisms of internalization of Neisseria gonorrhoeae by members of the CEACAM receptor family involving Rac1- and Cdc42-dependent and -independent pathways.

    Billker O, Popp A, Brinkmann V, Wenig G, Schneider J et al.

    The EMBO journal 2002;21;4;560-71

  • Signal transduction pathways induced by virulence factors of Neisseria gonorrhoeae.

    Popp A, Billker O and Rudel T

    International journal of medical microbiology : IJMM 2001;291;4;307-14

  • Both mosquito-derived xanthurenic acid and a host blood-derived factor regulate gametogenesis of Plasmodium in the midgut of the mosquito.

    Arai M, Billker O, Morris HR, Panico M, Delcroix M et al.

    Molecular and biochemical parasitology 2001;116;1;17-24

  • The structural basis of CEACAM-receptor targeting by neisserial Opa proteins.

    Billker O, Popp A, Gray-Owen SD and Meyer TF

    Trends in microbiology 2000;8;6;258-60; discussion 260-1

  • Determination of mosquito bloodmeal pH in situ by ion-selective microelectrode measurement: implications for the regulation of malarial gametogenesis.

    Billker O, Miller AJ and Sinden RE

    Parasitology 2000;120 ( Pt 6);547-51

  • Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito.

    Billker O, Lindo V, Panico M, Etienne AE, Paxton T et al.

    Nature 1998;392;6673;289-92

  • The roles of temperature, pH and mosquito factors as triggers of male and female gametogenesis of Plasmodium berghei in vitro.

    Billker O, Shaw MK, Margos G and Sinden RE

    Parasitology 1997;115 ( Pt 1);1-7

Billker, Oliver
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