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Recent achievements We have continued to develop a rodent model (Plasmodium chabaudi) of malaria, continuing the work of Profs David Walliker and Richard Carter in Edinburgh.

Numbers in square brackets [eg] refer to publications below Our achievements (some of which have involved a strong and developing collaboration with scientists in Lisbon and other laboratories) include

  • Selection of drug resistant mutants of P. chabaudi [1, 10]
  • Identification and investigation of genetic loci underlying drug resistance [6, 8, 9, 10]
  • Development of molecular markers for different strains of rodent malaria parasites, development of genetic linkage map, physical mapping of markers in malaria genome [4, 11]
  • Development of quantitative markers (AFLP, proportional sequencing and pyrosequencing) to estimate the proportions of alleles in the uncloned progeny of genetic crosses [2, 7]
  • Development of Linkage Group Selection (LGS) – a novel strategy for mapping genetic loci underlying selectable phenotypes such as drug resistance [5, 6]
  • Characterisation of the fitness costs of mutations underlying drug resistance [3] Present projects We are currently investigating the genetic basis of Artemisinin resistance in P. chabaudi in collaboration with Pedro Cravo’s laboratory in Lisbon We are also investigating the fitness costs of drug resistance markers in P. chabaudi

Paul Hunt

  1. Hunt P, Afonso A, Culleton R, Creasey A, Fidock D, Carter R, do Rosário V and Cravo P (2006) Molecular and genetic analysis of malaria parasites resistant to artemisinin. Proc. 11th International Congress of Parasitology (ICOPA XI), Glasgow, UK Medimond 425 – 427
  2. Afonso A, Hunt P, Cheesman S, Alves AC, Cunha CV, do Rosário V and Cravo P. (2006) Malaria parasites can develop stable resistance to artemisinin but lack mutations in candidate genes atp6 (encoding the sarcoplasmic and endoplasmic reticulum Ca 2+ ATPase), tctp, mdr1 and cg10. Antimicrobial Agents and Chemotherapy 50 480-489
  3. Hunt P, Fawcett R, Carter R and Walliker D. (2005) Sequencing estimates the relative concentration of SNPs in populations of malaria parasites; validation and applications. Mol. Biochem. Parasitol. 143 173-182
  4. Walliker D, Hunt P, and Babiker HA. (2005) Fitness of drug resistant malaria parasites. Acta Tropica 94 251-2509
  5. Martinelli A, Hunt P, Fawcett R, Cravo P, Walliker D and Carter R. (2005) An AFLP-based Genetic Linkage Map of Plasmodium chabaudi chabaudi Malaria Journal 4 11 -20
  6. Martinelli A, Cheesman S, Hunt P, Culleton R, Raza A, Mackinnon M and Carter R. (2005) A genetic approach to the de novo identification of targets of strain-specific immunity in malaria parasites Proc. Natl. Acad. Sci. (USA) 102 814-819
  7. Culleton R, Martinelli A, Hunt P and Carter R (2005) Linkage group selection: rapid gene discovery in malaria parasites Genome Research 15 92-97
  8. Martinelli A, Hunt P, Cheesman S and Carter R. (2004) Amplified Fragment Length Polymorphism measures proportions of malaria parasites carrying specific alleles in complex genetic mixtures Mol. Biochem. Parasitol. 136 117-122
  9. Hunt P, Martinelli A, Carlton JM-R, Fawcett R, Carter R and Walliker D. (2004) Gene synteny and chloroquine resistance in Plasmodium chabaudi Mol. Biochem. Parasitol. 136 157-164
  10. Hunt P, Cravo PVL, Donleavy P, Carlton JM-R and Walliker D. (2004) Chloroquine resistance in Plasmodium chabaudi : are chloroquine resistance transporter (crt) and multi-drug resistance (mdr1) orthologues involved? Mol. Biochem. Parasitol. 133 27-35
  11. Cravo PVL, Carlton JM-R, Hunt P, Bisoni L, Padua RA and Walliker D. (2003) Genetics of mefloquine resistance in the rodent malaria Plasmodium chabaudi. Antimicrobial Agents and Chemotherapy 47 709-718
  12. Grech K, Martinelli A, Pathirana S, Walliker D, Hunt P and Carter R. (2002) Numerous, robust genetic markers for Plasmodium chabaudi by the method of Amplified Fragment Length Polymorphism. Mol. Biochem. Parasitol. 123 95-104
  13. Abdel-Muhsin AMA, Ranford-Cartwright LC, Medani AR, Ahmed S, Suleiman S, Khan B, Hunt P, Walliker D and Babiker HA. (2002) Detection of mutations in the Plasmodium falciparum dihydrofolate reductase (dhfr) gene by dot-blot hybridisation. Am. J. Trop. Med. Hyg. 67 24-27
  14. Cravo P, Culleton R, Hunt P, Walliker D and Mackinnon MJ. (2001) Antimalarial drugs clear resistant parasites from partially immune hosts. Antimicrobial Agents and Chemotherapy 45 2897-2901
  15. Babiker HA, Pringle SA, Abdel-Muhsin A, Mackinnon M, Hunt P and Walliker D. (2001) High level chloroquine resistance in Sudanese isolates of Plasmodium falciparum is associated with mutations in the chloroquine resistance transporter gene, pfcrt, and the multidrug resistance gene, pfmdr1. J. Infect. Dis. 183 1535-1538

In press

Carter R, Hunt P and Cheesman S Linkage Group Selection - a fast approach to the genetic analysis of malaria parasites. Int. J. Parasitol. Xx xxx-xxx

Accepted subject to revision

Cheesman S, Creasey A, Degnan K, Afonso A, Cravo P, Carter R and Hunt P Genome-wide quantitative Pyrosequencing markers – validation for mapping genes in malaria parasites. Mol. Biochem. Parasitol. Xx xxx-xxx

Alison Creasey

  1. Gerloff DL, Creasey A, Maslau S and Carter R. (2005). Structural models for the protein family characterized by gamete surface protein Pfs230 of Plasmodium falciparum. Proc Natl Acad Sci U S A. 102 13598-603
  2. Creasey A, Giha H, Hamad AA, El Hassan IM, Theander TG and Arnot DE. (2004) Eleven years of malaria surveillance in a Sudanese village highlights unexpected variation in individual disease susceptibility and outbreak severity. Parasitology 129 263-71.
  3. Sowa MP, Sharling L, Humphreys G, Cavanagh DR, Gregory WF, Fenn K, Creasey AM and Arnot DE. (2004). High throughput immuno-screening of cDNA expression libraries produced by in vitro recombination; exploring the Plasmodium falciparum proteome. Mol Biochem Parasitol 133 267-74.
  4. Creasey AM, Staalsoe T, Raza A, Arnot DE and Rowe JA.(2003). Nonspecific immunoglobulin M binding and chondroitin sulfate A binding are linked phenotypes of Plasmodium falciparum isolates implicated in malaria during pregnancy. Infect Immun. 71 4767-71.
  5. Hamad AA, Nugud Ael H, Arnot DE, Giha HA, Abdel-Muhsin AM, Satti GM, Theander TG, Creasey AM, Babiker HA and Elnaiem DE.(2002). A marked seasonality of malaria transmission in two rural sites in eastern Sudan. Acta Trop. 83 71-82.
  6. Sowa KM, Cavanagh DR, Creasey AM, Raats J, McBride J, Sauerwein R, Roeffen WF and Arnot DE. (2001). Isolation of a monoclonal antibody from a malaria patient-derived phage display library recognising the Block 2 region of Plasmodium falciparum merozoite surface protein-1. Mol Biochem Parasitol. 112 143-7
  7. Cheng Q, Lawrence G, Reed C, Stowers A, Ranford-Cartwright L, Creasey A, Carter R and Saul A. (1997). Measurement of Plasmodium falciparum growth rates in vivo: a test of malaria vaccines. Am J Trop Med Hyg. 57 495-500.
  8. Creasey A, Mendis K, Carlton J, Williamson D, Wilson I and Carter R. (1994). Maternal inheritance of extrachromosomal DNA in malaria parasites. Mol Biochem Parasitol. 65 95-8.
  9. Bayoumi RA, Creasey AM, Babiker HA, Carlton JM, Sultan AA, Satti G, Sohal AK, Walliker D, Jensen JB, and Arnot DE.. (1993). Drug response and genetic characterization of Plasmodium falciparum clones recently isolated from a Sudanese village. Trans R Soc Trop Med Hyg. 87 454-8.
  10. Creasey AM, Ranford-Cartwright LC, Moore DJ, Williamson DH, Wilson RJ, Walliker D and Carter R. (1993). Uniparental inheritance of the mitochondrial gene cytochrome b in Plasmodium falciparum. Curr Genet. 23 360-4.
  11. Horgan G, Creasey A and Fenton B. (1992). Superimposing two-dimensional gels to study genetic variation in malaria parasites. Electrophoresis 13 871-5.
  12. Babiker HA, Creasey AM, Bayoumi RA, Walliker D and Arnot DE.(1991) Genetic diversity of Plasmodium falciparum in a village in eastern Sudan. 2. Drug resistance, molecular karyotypes and the mdr1 genotype of recent isolates. Trans R Soc Trop Med Hyg. 85 578-83.
  13. Babiker HA, Creasey AM, Fenton B, Bayoumi RA, Arnot DE and Walliker D. (1991) Genetic diversity of Plasmodium falciparum in a village in eastern Sudan. 1. Diversity of enzymes, 2D-PAGE proteins and antigens. Trans R Soc Trop Med Hyg. 85 572-7. Erratum in: Trans R Soc Trop Med Hyg 85 713.
  14. Creasey A, Fenton B, Walker A, Thaithong S, Oliveira S, Mutambu S and Walliker D. (1990). Genetic diversity of Plasmodium falciparum shows geographical variation. Am J Trop Med Hyg. 42 403-13.
  15. Carter R, Graves PM, Creasey A, Byrne K, Read D, Alano P and Fenton B(1989). Plasmodium falciparum: an abundant stage-specific protein expressed during early gametocyte development. Exp Parasitol. 69 140-9.
  16. Creasey AM, Taylor P and Thomas JE. (1986). Dosage trial of a combination of oxamniquine and praziquantel in the treatment of schistosomiasis in Zimbabwean schoolchildren. Cent Afr J Med. 32 165-7.
  17. Creasey AM, Wessels JM and Clarke VD. (1982). Re-evaluation of criteria for making a diagnosis of bilharzia. Cent Afr J Med. 28 265-72 18. Creasey AM, Thomas JE and Henry JA. Chronic organophosphate exposure and its effect on S. haematobium infection.(1982). Cent Afr J Med. 28 53-5.

Accepted subject to revision

Cheesman S, Creasey A, Degnan K, Afonso A, Cravo P, Carter R and Hunt P Genome-wide quantitative Pyrosequencing markers – validation for mapping genes in malaria parasites. Mol. Biochem. Parasitol. Xx xxx-xxx