Contribution Leiden studies

Author Chris Janse


Studies using the Plasmodium berghei malaria model in the Leiden malaria group (1982-2021) have resulted in:
i.    Development of novel technologies for malaria research
ii.   New insights into malaria parasite biology
iii. Contribution to the development and testing of (novel) vaccination approaches

i. Development of novel technologies for malaria research

  • In vitro culture of blood stages of P. berghei
    (PMID: 6343271; 6381348; 3909068; 15275357)
  • In vitro culture of zygotes and ookinetes of P. berghei
    (PMID: 2863802; 3906518)
  • Flowcytometry in malaria analysis and detection
    PMID: 7533245 (Methods Cell Biol.); 17406288 (Nat Protocol.)
  • Separation of rodent malaria chromosomes by Pulsed Field Gel electrophoresis
    PMID: 2649389; 1974695; 1741291 (Nucleic Acids Res.)
  • Transfection/genetic modification of malaria parasites
    PMID: 7761856 (Science.); 8571132 (Science); 16242190; 16537837 (Nucleic Acids Res.); 17406255 (Nat Protoc.); 21418605 (BMC Genomics.); 22216235
  • Creation of transgenic malaria parasites, stably expressing reporter proteins such as GFP, Luciferase, Ovalbumin
    PMID 10377003; 1527994817406288 (Nat Protoc.); 17406270 (Nat protoc.); 25156724
  • Generation of transgenic malaria parasites with a stable artificial chromosome
    PMID: 20227667 (Cell Host Microbe.)
  • In vivo imaging in live animals of rodent malaria parasites expressing luciferase
    PMID: 17406270 (Nat Protoc.); 19924309; 22990791 (Methods Mol Biol.); 22990796 (Methods Mol Biol.); 22990801 (Methods Mol Biol.)
  • Creation of chimeric rodent malaria parasites, stably expressing proteins of human malaria parasites
    PMID: 26450395 (Methods Mol Biol.); 28525963 (Expert Rev Vaccines.)
  • Creation of genetically attenuated malaria parasites
    PMID: 16103357 (PNAS); 21152048; 22560204 (Curr Opin Biotechnol.); 25407681 (Elife); 28525963 (Expert Rev Vaccines.); 32434847 (Sci Transl Med.)

ii. New insights into the biology of malaria parasites

  • DNA synthesis/genome replication in malaria male gametocytes/gametes
    (PMID: 3088783; 3092048)
  • Meiotic DNA replication in malaria zygotes
    (PMID: 3092048)
  • Identification of fourteen P. berghei chromosomes and (mechanisms of) chromosome size polymorphisms
    PMID: 2649389; 1974695; 2174115 (Mol Cell Biol.); 1741291 (Nucleic Acids Res.); 7739674; 10984459 (Genome Res.)
  • Genome sequences of various rodent malaria parasites
    PMID: 12368865 (Nature.); 15637271 (Science); 16389297 (PLoS Pathog.); 25359557 (BMC Biol.)
  • Proteomes of male and female malaria gametes
    PMID: 15935755 (Cell.)
  • The role of proteins in malaria gamete fertilization (for example, P48/45 and P47)
    PMID: 11163248 (Cell.); 20386715 (PLoS Pathog.)
  • Proteome of sporozoites
    PMID: 18974882 (PLoS Pathog.)
  • The function of the major sporozoite surface protein (CSP) in sporozoite formation
    PMID: 9002517 (Nature)
  • The role of ookinete surface proteins P25/P28 in malaria mosquito infection
    PMID: 8341324; 11483501 (EMBO J.)
  • Post-transcriptional gene regulation (translational repression) in female gametes, zygotes and sporozoites
    PMID: 16888139 (Science.); 18158300 (Nucleic Acids Res.); 20169188 (PLoS Pathog.); 21625527 (PLoS Pathog.); 25418785 (Genome Biol.); 26808677
  • The role of the glutathione biosynthetic pathway in malaria mosquito transmission
    PMID: 19229315 (PLoS Pathog.); 20573956 (J. Biol Chem.)
  • The role of malaria parasite rhomboids and palmitoyl-S-acyl-transferases (DHHC)
    PMID: 23490234; 26526684; 27303037 (Proc Natl Acad Sci U S A.)
  • Proteins involved in CD36-mediated sequestration of P. berghei schizonts and the in vivo role of  schizont-sequestration
    PMID: 16051702 (Proc Natl Acad Sci U S A.); 20941396 (PLosPathog.); 22184632 (J Exp Med.); 27225796 (Nat Commun.)
  • Malaria proteins with a (essential) role for development in hepatocytes
    PMID: 16103357 (Proc Natl Acad Sci U S A.); 18958160; 19064257 (Cell Host Microbe.); 24509910 (FASEB J.); 25786000 (PLoS Pathog.); 26332724; 31730853 (Cell.)
  • Functional analysis of centromeres and generation of an artificial chromosome
    PMID: 20227667 (Cell Host Microbe.)
  • Malaria proteins exported into host cells (erythrocytes, hepatocytes; Plasmodium multigene families)
    PMID: 18551176 (PLoS Pathog.); 18563749 (Proteomics); 23197789 (Mol Cell Proteomics.); 27851824 (PLoS Pathog.)
  • Malaria proteins involved in hemoglobin digestion
    PMID: 25941254 (J Exp Med.)
  • The role of glutaminyl cyclase-mediated posttranslational protein modification (of the major sporozoite surface protein, CSP) in evading mosquito immunity
    PMID: 35994647

iii. Contribution to development and testing of (novel) vaccination approaches

  • Chimeric rodent parasites expressing putative vaccine candidate antigens of human malaria parasites (P. falciparum and P. vivax), used to develop and evaluate viral-vectored(ChAd63 and MVA)-, protein-, mRNA- and VLP-based vaccines
    PMID: 26450395 (Methods Mol Biol.);  28525963 (Expert Rev Vaccines.); 30257955 (Sci Transl Med.); 29195810 (Immunity.); 30469323 (Diseases.); 28417968; 28179403 (Clin Vaccine Immunol.)
  • Development and evaluation of a P. berghei-based whole-sporozoite malaria vaccine candidate
    PMID: 30155278 (NPJ Vaccines.); 30510775 (NPJ Vaccines.)
  • Development and preclinical evaluation of genetically attenuated parasites (GAP)  and the first clinical evaluation of a human malaria GAP (PfSPZ-GA1) for vaccination
    PMID: 16103357 (Proc Natl Acad Sci U S A.); 18958160; 21152048; 22342550 (Vaccine.); 22560204 (Curr Opin Biotechnol.); 24509910 (FASEB J.); 25407681 (Elife.); 27296385; 28871201; 32434847 (Sci Transl Med.)
  • Development and preclinical evaluation of a second generation GAP vaccine, GA2 (genetically attenuated parasites; GAP).
    (NPJ Vaccine in press)