Dr. Chris J Janse

Research interests

Klik hier voor informatie in het Nederlands

Website of the Malaria Research Group

The current emphasis of my research is on the identification and characterization of malarial vaccine candidates through the functional analysis of parasite antigens using a rodent model of malaria. This research combines genetic modification technologies and post-genome analyses (microarray and proteome analyses) with biochemical and biological assays. One project within the Leiden Malaria Research Group, analyses parasites that have been ‘attenuated’ (through genetic modification) and that demonstrate a vaccine potential when injected as whole live parasites into mice for their role in the development of (protective) immunity. Another project on host-parasite interactions we examine the sequestration of infected red blood cells to small blood vessels of the host, a process that leads to malaria-associated pathology. Specifically, by combining transgenic malaria parasites that express fluorescent/bioluminescent reporter proteins with novel imaging technologies, we are able to visualise interactions between the host and parasite in live mice. These studies have resulted in novel insights into tissue and host-cell receptors involved in sequestration of infected erythrocytes.

See below for 'Selected publications' and 'Professional Biosketch'.

Information in Dutch.
Voor meer informatie in het nederlands over het malaria onderzoek in Leiden: zie ook 'Leids malaria onderzoek in het nieuws'

Dr. Chris Janse is hoofd van de Malaria Onderzoeksgroep van de afdeling Parasitologie van het Leids Universitair Medisch Centrum (LUMC) in Leiden. De groep onderzoekt eiwitten van de malariaparasiet die als targets kunnen dienen voor nieuwe medicijnen en voor het ontwikkelen van een vaccin. Bij dit onderzoek wordt gebruik gemaakt van een malariaparasiet van knaagdieren, Plasmodium berghei, welke wereldwijd gebruikt wordt als een model voor onderzoek aan malaria bij mensen. De onderzoeksgroep heeft een (internationaal) leidende positie in de ontwikkeling en toepassing van dit onderzoeksmodel.

Tijdens zijn promotie onderzoek ontwikkelde Chris Janse nieuwe technieken voor het in-vitro kweken en produceren van malaria parasieten en bestudeerde hij DNA replicatie in deze parasieten. Als eerste ontwikkelde hij methoden voor het kweken van de bloedstadia en het isoleren van chromosomen van een malaria parasiet van knaagdieren. Na zijn promotie (cum laude) heeft hij het malariamodel van knaagdieren verder geoptimaliseerd voor onderzoek naar de biologie van malariaparasieten en onderzoek naar de interacties tussen de parasiet en zijn gastheer. Een belangrijke doorbraak was de ontwikkeling van methoden voor genetische modificatie van malariaparasieten. Deze technieken hebben nieuwe wegen geopend voor het onderzoek naar nieuwe medicijnen en vaccins. Chris Janse is betrokken bij grootschalige analyses van genen (genoom sequentie analyse) en eiwitten (proteoom analyses) van malaria parasieten en ontwikkeld nieuwe methoden voor het zichtbaar maken van interacties van de parasiet met (cellen van) de gastheer (‘molecular imaging’). Het onderzoek heeft tot publicaties geleid in wetenschappelijk toptijdschriften zoals in Science, Nature, Journal of Experimental Medicine en PNAS.

Een project van de Leidse malaria onderzoeksgroep heeft als doel het ontwikkelen van een malariavaccin dat gebaseerd is vaccinatie met verzwakte parasieten. Onderzoek heeft aangetoond dat vaccinatie met verzwakte parasieten immuunreacties opwekken die een goede bescherming kunnen bieden tegen malaria infecties. De parasieten in dit vaccin worden verzwakt (geattenueerd) door middel van genetische modificaties van de parasiet. Een ander project onderzoekt ziekteverschijnselen (pathologie) van malaria infecties die veroorzaakt worden door ophoping van geïnfecteerde bloedcellen in kleine bloedvaatjes van vitale organen, zoals de longen en hersenen. Het verkrijgen van meer inzicht in factoren die hierbij betrokken zijn is belangrijk voor de behandeling van ernstige complicaties van malaria infecties.

Chris Janse heeft een  Malaria Website Resource Center opgezet dat wetenschappelijk informatie verschaft over het Plasmodium berghei model van malaria en hij onderhoud een database met informatie van alle genetisch gemodificeerde mutanten van malariaparasieten van knaagdieren. Deze database www.pberghei.eu is voor iedereen toegankelijk via het internet. Daarnaast heeft hij een website opgezet voor de Nederlandse Vereniging voor Parasitologie. Deze website geeft informatie over infecties bij mens en dier die veroorzaakt worden door parasieten.

Selected publications

Dijk, M.R. van, Waters, A.P. and Janse, C.J. (1995). Stable transfection of malaria parasite blood stages. Science 268, 1358-1362.

Dijk, M.R. van, Janse, C.J. and Waters, A.P. (1996). Expression of a Plasmodium gene introduced into subtelomeric regions of Plasmodium berghei chromosomes. Science 271, 662-665.

Wel, A.M. van der, Tomas, A.M., Kocken, C.H.M., Malhotrall, P., Janse, C.J., Waters, A.P. and A.W. Thomas (1997). Transfection of the primate malaria parasite Plasmodium knowlesi using entirely heterologous constructs. J.Exp.Med. 185, 1499-1503

Menard, R., Sultan, A.A., Cortes, C., Altszuler, R., van Dijk, M.R., Janse, C.J., Waters, A.P., Nussenzweig, R.S. and Nussenzweig, V. (1997). Circumsporozoite protein is required for development of malaria sporozoites in mosquitoes. Nature 385, 336-340.

Wengelnik, K., Spaccapelo, R., Naitza, S., Robson, K.J.H., Janse, C.J., Waters, A.P. & Crisanti, A. (1999). TRAP complementation in Plasmodium berghei and mutation analysis reveals a role of the conserved adhesive domains in the invasion of mosquito salivary glands. EMBO J. 18, 5195-204

Tomas, A.M., Margos, G., Dimopoulos, G., Lin, L.H.M. van, de Koning-Ward, T.F., Sinha, R., Lupetti, P., Beetsma, A.L., Rodriguez, M.C., Karras, M., Hagar, A., Mendoza, J., Butcher, G.A., Kafatos, F.C., Janse, C.J., Waters, A.P. and Sinden, R.E. (2001). The conserved P25/P28 proteins of the malaria ookinete surface have multiple and partially redundant functions. EMBO Journal 20, 3975-83.

Dijk, M.R.,  Janse, C.J., Thompson, J., Waters, A.P., Braks, J.A.M., Dodemont, H.J., Stunnenberg, H.G., Gemert, G.J. van, Sauerwein, R.W. and Eling, W. (2001). A central role for P48/45 in malaria parasite male gamete fertility. Cell 104, 153-164

Carlton JM, Angiuoli SV, Suh BB, Kooij TW, Pertea M, Silva JC, Ermolaeva MD, Allen JE, Selengut JD, Koo HL, Peterson JD, Pop M, Kosack DS, Shumway MF, Bidwell SL, Shallom SJ, van Aken SE, Riedmuller SB, Feldblyum TV, Cho JK, Quackenbush J, Sedegah M, Shoaibi A, Cummings LM, Florens L, Yates JR, Raine JD, Sinden RE, Harris MA, Cunningham DA, Preiser PR, Bergman LW, Vaidya AB, van Lin LH, Janse CJ, Waters AP, Smith HO, White OR, Salzberg SL, Venter JC, Fraser CM, Hoffman SL, Gardner MJ, Carucci DJ. Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii. Nature. 2002, 419:512-9.

Blandin S, Shiao SH, Moita LF, Janse CJ, Waters AP, Kafatos FC, Levashina EA (2004) Complement-like protein TEP1 is a determinant of vectorial capacity in the malaria vector Anopheles gambiae. Cell. 116: 661-70.

Kooij TW, Carlton JM, Bidwell SL, Hall N, Ramesar J, Janse CJ, Waters AP (2005) A Plasmodium Whole-Genome Synteny Map: Indels and Synteny Breakpoints as Foci for Species-Specific Genes. PLoS Pathog. 23;1(4): e44

van Dijk MR, Douradinha B, Franke-Fayard B, Heussler V, van Dooren MW, van Schaijk B, van Gemert GJ, Sauerwein RW, Mota MM, Waters AP, Janse CJ. (2005). Genetically attenuated, P36p-deficient malarial sporozoites induce protective immunity and apoptosis of infected liver cells. Proc Natl Acad Sci U S A, 102:12194-9

Franke-Fayard B, Janse CJ, Cunha-Rodrigues M, Ramesar J, Buscher P, Que I, Lowik C, Voshol PJ, den Boer MA, van Duinen SG, Febbraio M, Mota MM, Waters AP.(2005). Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration. Proc Natl Acad Sci U S A. 102. 11468-73

Khan, S.M., Franke-Fayard, B., Mair, G.R., Lasonder, E., Janse, C.J, Mann, M. & Waters, A.P. (2005) Proteome analysis of separated male and female gametocytes reveals novel sex specific Plasmodium biology. Cell 121: 675-87

Hall, N., Karras, M., Raine, J.D., Carlton, J.M., Kooij, T.W.A., Berriman, M., Florens, L., Janssen, C., Pain, A., Christophides, C.K., James, K., Rutherford, K., Harris, B., Harris, D., Churcher, C., Quail, M.A., Ormond, D., Doggett, J., Trueman, H.E., Mendoza, J., Bidwell, S., Rajandream, M.A., Carucci, D.A., Yates, J.R. III, Kafatos, F.C., Janse, C.J., Barrell, B., Turner, C.M.R., Waters, A.P., Sinden, R.E. (2005) A comprehensive survey of the Plasmodium  life cycle by genomic, transcriptomic and proteomic analyses. Science 307. 82-6.

Waters, A.P. Mota, M.M., van Dijk, M.R. & Janse C.J. (2005) Malaria Vaccines: Back to the Future? – Perspective. Science 307:528-30

Mair GR, Braks JA, Garver LS, Wiegant JC, Hall N, Dirks RW, Khan SM, Dimopoulos G, Janse CJ, Waters AP (2006). Regulation of sexual development of Plasmodium by translational repression. Science 313: 667-9.

Kooij TW, Janse CJ, Waters AP (2006). Plasmodium post-genomics: better the bug you know? Nat Rev Microbiol. 4: 344-57. Review.

Janse CJ, Franke-Fayard B, Waters AP. Selection by flow-sorting of genetically transformed, GFP-expressing blood stages of the rodent malaria parasite, Plasmodium berghei. Nat Protoc. 2006;1(2):614-23.

Franke-Fayard B, Waters AP, Janse CJ. Real-time in vivo imaging of transgenic bioluminescent blood stages of rodent malaria parasites in mice. Nat Protoc. 2006;1(1):476-85.

Janse CJ, Ramesar J, Waters AP.  High-efficiency transfection and drug selection of genetically transformed blood stages of the rodent malaria parasite Plasmodium berghei. Nat Protoc. 2006;1(1):346-56.

van Ooij C, Tamez P, Bhattacharjee S, Hiller NL, Harrison T, Liolios K, Kooij T, Ramesar J, Balu B, Adams J, Waters A, Janse C, Haldar K. The malaria secretome: from algorithms to essential function in blood stage infection. PLoS Pathog. 2008 Jun 13;4(6):e1000084.

van Schaijk BC, Janse CJ, van Gemert GJ, van Dijk MR, Gego A, Franetich JF, van de Vegte-Bolmer M, Yalaoui S, Silvie O, Hoffman SL, Waters AP, Mazier D, Sauerwein RW, Khan SM. Gene disruption of Plasmodium falciparum p52 results in attenuation of malaria liver stage development in cultured primary human hepatocytes. PLoS ONE. 2008;3(10):e3549.

Lasonder E, Janse CJ, van Gemert GJ, Mair GR, Vermunt AM, Douradinha BG, van Noort V, Huynen MA, Luty AJ, Kroeze H, Khan SM, Sauerwein RW, Waters AP, Mann M, Stunnenberg HG. Proteomic profiling of Plasmodium sporozoite maturation identifies new proteins essential for parasite development and infectivity. PLoS Pathog. 2008 Oct;4(10):e1000195.

Yu M, Kumar TR, Nkrumah LJ, Coppi A, Retzlaff S, Li CD, Kelly BJ, Moura PA, Lakshmanan V, Freundlich JS, Valderramos JC, Vilcheze C, Siedner M, Tsai JH, Falkard B, Sidhu AB, Purcell LA, Gratraud P, Kremer L, Waters AP, Schiehser G, Jacobus DP, Janse CJ, Ager A, Jacobs WR Jr, Sacchettini JC, Heussler V, Sinnis P, Fidock DAThe fatty acid biosynthesis enzyme FabI plays a key role in the development of liver-stage malarial parasites.. Cell Host Microbe. 2008 4:567-78.

Vega-Rodríguez J, Franke-Fayard B, Dinglasan RR, Janse CJ, Pastrana-Mena R, Waters AP, Coppens I, Rodríguez-Orengo JF, Jacobs-Lorena M, Serrano AE. The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission. PLoS Pathog. 2009, 5(2):e1000302.

Baum J, Papenfuss AT, Mair GR, Janse CJ, Vlachou D, Waters AP, Cowman AF, Crabb BS, de Koning-Ward TF. Molecular genetics and comparative genomics reveal RNAi is not functional in malaria parasites. Nucleic Acids Res. 2009;37(11):3788-98.

Moon RW, Taylor CJ, Bex C, Schepers R, Goulding D, Janse CJ, Waters AP, Baker DA, Billker O. A cyclic GMP signalling module that regulates gliding motility in a malaria parasite. PLoS Pathog. 2009 Sep;5(9):e1000599.

Spaccapelo R, Janse CJ, Caterbi S, Franke-Fayard B, Bonilla JA, Syphard LM, Di Cristina M, Dottorini T, Savarino A, Cassone A, Bistoni F, Waters AP, Dame JB, Crisanti A. Plasmepsin 4-deficient Plasmodium berghei are virulence attenuated and induce protective immunity against experimental malaria. Am J Pathol. 2010;176(1):205-17.

Iwanaga S, Khan SM, Kaneko I, Christodoulou Z, Newbold C, Yuda M, Janse CJ, Waters AP (2010). Functional identification of the Plasmodium centromere and generation of a Plasmodium artificial chromosome. Cell Host Microbe. 7(3):245-55.

Mair GR, Lasonder E, Garver LS, Franke-Fayard BM, Carret CK, Wiegant JC, Dirks RW, Dimopoulos G, Janse CJ, Waters AP. Universal features of post-transcriptional gene regulation are critical for Plasmodium zygote development. PLoS Pathog. 2010;6(2):e1000767.

Dijk MR van, BSchaijk BCL van, Khan SM, Dooren MW van, Ramesar J, Kaczanowski S, Gemert GJ van, Kroeze H, Stunnenberg HG, Eling WM, Sauerwein RW, Waters AP, Janse CJ. Three Members of the 6-cys Protein Family of Plasmodium Play a Role in Gamete Fertility. Plos Pathogens. 2010 Apr 8;6(4):e1000853.

Pastrana-Mena R, Dinglasan RR, Franke-Fayard B, Vega-Rodriguez J, Fuentes-Caraballo M, Baerga-Ortiz A, Coppens I, Jacobs-Lorena M, Janse CJ, Serrano AE. Glutathione reductase-null malaria parasites have normal blood stage growth but arrest during development in the mosquito. J Biol Chem. 2010 ; 285: 27045-56

Franke-Fayard B, Fonager J, Braks A, Khan SM, Janse CJ. Sequestration and tissue accumulation of human malaria parasites: can we learn anything from rodent models of malaria? PLoS Pathog. 2010;  6(9). pii: e1001032.

Gueirard P, Tavares J, Thiberge S, Bernex F, Ishino T, Milon G, Franke-Fayard B, Janse CJ, Ménard R, Amino R. Development of the malaria parasite in the skin of the mammalian host. Proc Natl Acad Sci U S A. 2010;107(43):18640-5.

Janse CJ, Kroeze H, van Wigcheren A, Mededovic S, Fonager J, Franke-Fayard B, Waters AP, Khan SM. A genotype and phenotype database of genetically modified malaria-parasites. Trends Parasitol. 2011, 27(1):31-9.

Gomes-Santos CS, Braks J, Prudêncio M, Carret C, Gomes AR, Pain A, Feltwell T, Khan S, Waters A, Janse C, Mair GR, Mota MM. Transition of Plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein pumilio.PLoS Pathog. 2011; 7(5):e1002046.

Wykes MN, Kay JG, Manderson A, Liu XQ, Brown DL, Richard DJ, Wipasa J, Jiang SH, Jones MK, Janse CJ, Waters AP, Pierce SK, Miller LH, Stow JL, Good MF. Rodent blood-stage Plasmodium survive in dendritic cells that infect naive mice. Proc Natl Acad Sci U S A. 2011 108(27):11205-10.

Fonager J, Pasini EM, Braks JA, Klop O, Ramesar J, Remarque EJ, Vroegrijk IO, van Duinen SG, Thomas AW, Khan SM, Mann M, Kocken CH, Janse CJ, Franke-Fayard BM. Reduced CD36-dependent tissue sequestration of Plasmodium-infected erythrocytes is detrimental to malaria parasite growth in vivo. J Exp Med. 2011 Dec 19.

Professional biosketch

My undergraduate studies were on Biology at the University of Leiden, The Netherlands. After which my graduate research was spread over a few disciplines, specifically; the ecology and host-seeking behaviour of sibling species of parasitic wasps, ecology of bird populations (relationships between species diversity and forest management) and cell-biology of malaria parasites (genetic and environmental factors underlying sexual differentiation).

It was during my Ph.D. studies that I developed technologies for use on the rodent model of malaria (Plasmodium berghei; in Wikipedia) to investigate sexual differentiation and DNA replication in malaria parasites. These studies were funded by the Netherlands Organization for Scientific Research and were carried out jointly between the University of Utrecht and the University of Leiden. During my Ph.D. period I developed methods for the in vitro cultivation of blood- and mosquito stages of P. berghei together with Dr. B. Mons. These technologies have significantly increased the relevance of P. berghei as a model of human malaria and were pivotal in improving our understanding of the developmental biology of malaria parasites at the molecular level. The work performed during my thesis provided an insight into the process of DNA replication during parasite sexual development and technologies were developed then permitted me to perform the first separation and characterization of the chromosomes of rodent malaria parasites. For my work on the development of P. berghei as a rodent model of malaria I was awarded the Eijkman Medal by the Netherlands Society of Tropical Medicine.

After my Ph.D. (‘cum laude’) I have continued to use and develop the malaria rodent model to investigate the biology of malaria parasites in the Department of Parasitology (LUMC, Leiden), together with Dr. Andy Waters. Our research has contributed to the introduction and application of advanced molecular techniques in malaria research. A major breakthrough in our laboratory was the implementation of technologies that permit genetic modification of rodent malaria parasites; technologies that allowed, for the first time, the generation of malaria parasites that retain stable genetic modifications. These methodologies and others that we developed have opened up new avenues in malarial research and have greatly aided in the functional analysis of potential parasite drug and vaccine targets. For the research on genetic modification of malaria parasites I was awarded the W.R.O. Goslings price from the Dutch and Flanders Society for Infectious Diseases.

The current emphasis of my research is on the identification and characterization of malarial vaccine candidates through the functional analysis of parasite antigens. This research combines genetic modification technologies and post-genome analyses (microarray and proteome analyses) with biochemical and biological assays. One project within the Leiden Malaria Research Group, analyses parasites that have been ‘attenuated’ (through genetic modification) and that demonstrate a vaccine potential when injected as whole live parasites into mice for their role in the development of (protective) immunity. Another project on host-parasite interactions we examine the sequestration of infected red blood cells to small blood vessels of the host, a process that leads to malaria-associated pathology. Specifically, by combining transgenic malaria parasites that express fluorescent/bioluminescent reporter proteins with novel imaging technologies, we are able to visualise interactions between the host and parasite in live mice. These studies have resulted in novel insights into tissue and host-cell receptors involved in sequestration of infected erythrocytes.

Other professional activities

- I have built a Malaria Website Resource Center, which provides general information about the Plasmodium berghei rodent model. Within it are contained detailed protocols for biological assays, molecular techniques and information about our standard ‘in-house’ plasmids necessary for a variety of genetic modifications in P. berghei. In addition, the website also provides databases containing information on the P. berghei genome and on individual genes, such as chromosome location and transcription/expression profiles. A significant number of standard plasmids for genetic modification and transgenic P. berghei parasite lines from the Leiden Malaria Research Group are available to the malaria research community and have been deposited at the Malaria Research and Reference Reagent resource Center, MR4. 

- In addition, I have made and maintain/curate a web-based database (RMgmDB; wwwp.berghei.eu) containing information on genetically modified rodent malaria parasite lines generated by many labs worldwide. Specifically, it contains data of three rodent malaria parasite species; Plasmodium berghei, P. yoelii and P. chabaudi. The aim of this database is to provide the research community access to detailed information on the generation (e.g. disruption, tagging, mutation, transgene expression) and phenotype of genetically modified malaria parasites. The information in this database is shared with the ‘Sanger Institute Pathogen Genome Database’ (www.GeneDB.org) and ‘EuPathDB Bioinformatics Resource Center for biodefense and Emerging / Re-emerging Infectious Diseases’ (www.PlasmDB.org).

 - Co-editor (with Dr. A.P. Waters) of the book: "Malaria parasites: genomes and molecular biology” (Eds. A.P. Waters, C.J. Janse; 2004) p.546. Caister Academic Press, Wymondham, UK.

- Board member of the The Netherlands Society for Parasitology (NVP) and the ‘Stichting Kwaliteitsbewaking Medische Laboratoriumdiagnostiek’ (SKML).

- Co-editor of the website of the Netherlands Society of Parasitology.

- Member of the Advisory Board of the book: 'Medische Parasitologie' (2005; ed. Dr. A.M. Polderman), Syntax Media.