- Email: [email protected]
Rodent models of malaria in the genomics era
100
Research Update
Chemotherapy
Cryptosporidium is one of the few enteric protozoans for which no effective chemotherapy has been discovered (J.R. Mead, Emory University, Atlanta, GA, USA). The lack of adequate therapy puts humans and animals at risk when immune function is compromised. The lack of anti-cryptosporidial drugs could reflect the unique features of this parasite and include its cellular location and its phylogenetic affinities, which separate it from the coccidians. There is ample justification to evaluate new targets, novel classes of compounds and better ways of evaluating drug efficacy. In this respect, tubulin and tubulin-binding agents such as the dinitroanilines have potential (A. Armson, Murdoch University, Western Australia), and nitazoxanide could be a beneficial anticryptosporidial agent under certain circumstances (L. Favennec, Hospital Charles Nicolle, Rouen, France). Quantitative PCR procedures to evaluate drug efficacy in vitro have also been developed (L.M. MacDonald, Murdoch University, Western Australia). Synthesis
Closing discussions focused on nomenclature, taxonomy, establishing
TRENDS in Parasitology Vol.18 No.3 March 2002
databases, water industry needs, epidemiology and sources of infection, and directions for future research. There was general agreement that once Cryptosporidium genotypes were well characterized, it made sense to name them formally as distinct species. This has happened recently with Cryptosporidium canis and will now proceed for the human genotype (Type 1), Cryptosporidium hominis. It has been demonstrated that human infections with Type 1 and Type 2 isolates differ in their epidemiology: whether the clinical outcome also differs requires further investigation. However, although there was no resolution, the most controversial area is routine monitoring with respect to frequency and interpretation of results. Scientists might differ in their views but the final decision is driven by government legislation, and there is clearly insufficient data to convince some water authorities to lessen the stringency of their operations. The ability to genotype Cryptosporidium oocysts has provided a valuable epidemiological tool in studies on sources of infection and risk factors, which now needs to be expanded to include the exploration of sub-genotyping tools for epidemiological applications.
Cell culture, the oocyst structure, disinfection, chemotherapy, prophylaxis and molecular epidemiology were seen as the most important areas of future research. Acknowledgements
The Conference was generously supported by The Water Services Association of Australia, GlaxoSmithKline, The CRC for Water Quality and Treatment, American Water Works Association Research Foundation, Water Corporation of Western Australia, Australian Society for Microbiology and Murdoch University, Western Australia. The full proceedings from the conference will be published as a book Cryptosporidium: From Molecules to Disease edited by R.C.A. Thompson, A. Armson and U.M. Morgan-Ryan (Elsevier) during 2002. R.C. Andrew Thompson* Division of Veterinary and Biomedical Sciences, Murdoch University, Murdoch, Western Australia, 6150. *e-mail: [email protected] Rachel M. Chalmers Public Health Laboratory Service Cryptosporidium Reference Unit, Swansea PHL, Singleton Hospital, Swansea, UK SA2 8QA.
Rodent models of malaria in the genomics era Jane M. Carlton and Daniel J. Carucci The Rodent Malaria Genomics Symposium: Current Status and Future Directions was held on 15–16 November 2001 in Atlanta, GA, USA.
It has been apparent for the past few years in malaria research that basic biological knowledge of the rodent models of malaria lag far behind the very species they are intended to model. Why the study of the rodent malarias lags behind that of Plasmodium falciparum could partly be due to historical reasons and partly to a lack of acknowledgement concerning the usefulness of rodent model experimental data. Although direct extrapolation from rodent model biology to P. falciparum biology might not be applicable in all situations, each of the four rodent malaria species has similar characteristics to the four human malaria species, which http://parasites.trends.com
make them suitable for parallel study. For example, antigenic variation in Plasmodium chabaudi, in vivo drug testing with Plasmodium berghei, pre-erythrocytic stage vaccines with Plasmodium yoelii and chronobiology of Plasmodium vinckei. Following completion of the P. falciparum genome sequence and its imminent annotation and publication by the Malaria Genome Consortium [1], it would now seem an opportune time to pull together all available genomic information from diverse malaria species in an attempt to determine how these data can be used to develop better diagnostic tests, antimalarial drugs and vaccines. Current malaria genomics and proteomics studies
The Rodent Malaria Genomics symposium was opened by I. Landau (Natural History
Museum, Paris, France), who was the first to identify several African murine malaria species, including P. y. yoelii with R. Killick-Kendrick in 1966 [2]. From the basics of the rodent malaria life cycle, the symposium was brought sharply into the genomics era by presentations from three sequencing centers: The Institute for Genomic Research (TIGR), the Wellcome Trust Sanger Institute and Celera Genomics. A description of the P. yoelii genome sequencing project and simultaneous comparative genomics projects was given (J.M. Carlton, TIGR, Rockville, MD, USA). Approximately 3000 contigs with an average size of 7 kb are now available for this genome (see Box 1a) in addition to ~15 000 expressed sequence tags (ESTs) which represent the single largest EST dataset for a Plasmodium species (Box 1b). Comparative genomic
1471-4922/02/$ – see front matter © 2002 Published by Elsevier Science Ltd. PII: S1471-4922(01)02229-2
Research Update
TRENDS in Parasitology Vol.18 No.3 March 2002
101
Box 1. Websites of interest (a) The Institute for Genomic Research (TIGR) and Naval Medical Research Center Plasmodium yoelii genome sequencing program http://www.tigr.org/tdb/edb2/pya1/htmls/ (b) The TIGR Plasmodium yoelii gene index http://www.tigr.org/tdb/pygi/ (c) The Sanger Institute Plasmodium chabaudi partial genome shotgun project http://www.sanger.ac.uk/projects/p_chabaudi/ (d) The Sanger Institute Plasmodium berghei partial genome shotgun project http://www.sanger.ac.uk/projects/p_berghei/ (e) The Malaria Research and Reference Reagent Resource Center, MR4 http://www.malaria.mr4.org/mr4pages/index.html (f) The Plasmodium Genome Resource, PlasmoDB http://plasmodb.org
studies involving the creation of a global syntenic map between P. yoelii and P. falciparum are currently under way, which should aid the identification of orthologous genes between these species. This was followed by a description of the ongoing rodent malaria genome projects at the Sanger Institute Pathogen Sequencing Unit (N. Hall, Sanger Institute, Cambridge, UK). Partial shotgun sequencing of the P. chabaudi (Box 1c) and P. berghei (Box 1d) genomes to threefold coverage is expected to be available in the next few months, and a fivefold coverage of the primate malaria P. knowlesi has already finished. A discussion of the sevenfold mousegenome assembly generated from public and private sequencing efforts was also presented (R. Mural, Celera Genomics, Rockville, MD, USA). With the completion of a draft of the human genome [3,4], comparative genomics between mouse and human will enable direct correlations
between rodent malaria species (on a background of the host mouse genome), with human malaria species (on a background of the host human genome). To illustrate this, Mural chose a recent publication by one of the symposium attendees [5], which identified a mouse gene locus involved in host susceptibility to malaria. Synteny comparisons between the human and mouse genomes should now enable this and other loci to be mapped back to the human genome. Subsequent presentations were devoted to projects using the rodent malaria genome information in functional genomics projects. E. Winzeler (Scripps Research Institute, La Jolla, CA, USA) described an oligoarray chip consisting of 25-mers from genes of the P. falciparum and P. yoelii genomes, and the functional studies which could be done using these chips based on similar studies in yeast [6]. B. Bergman (MCP Hahnemann University, Philadelphia, PA, USA)
described the yeast two-hybrid studies and the cDNA microarray project under way in his lab, which uses 15 000 EST sequences and clones available for P. yoelii, recently submitted to GenBank dbEST (Table 1) and deposited with the Malaria Research and Reference Reagent Resource Center (MR4; Box 1e). L. Florens (Scripps Research Institute, CA, USA) outlined a high-throughput proteomic approach using MudPIT technology [7] to identify proteins from various stages of the P. yoelii life cycle, such as sporozoite, blood-stage and, soon, ookinete stages. Although supplies of these stages can be obtained from in vivo growth of the parasite, H. Hurd (University of Keele, UK) grabbed the attention of all participants by her elegant description of in vitro development of the P. berghei ookinete stage to infective sporozoite stage, without the need for development within the mosquito salivary glands. This means that the complete life cycle of P. berghei is now possible in vitro. Rodent malaria biology studies
The remainder of the symposium was put over to more biological presentations including immunology and vaccine studies, chemotherapy and drug resistance studies, and host–parasite biology. D. Haddad (Naval Medical Research Center, Silver Spring, MD, USA) gave an interesting presentation on using the open reading frames (ORFs) identified from P. yoelii genome data in high-throughput vaccinomic studies. Plasmid DNA from cloned ORFs are pooled and used as a DNA vaccine to immunize mice in an attempt to identify
Table 1. Plasmodium genome and functional genomics projectsa Species and line
Genome Project
Sequencing center
Plasmodium falciparum 3D7
6126
1782
P. falciparum patient isolate Plasmodium vivax Salvador I Plasmodium knowlesi H strain Plasmodium yoelii 17XNL
Whole TIGR, genome Sanger Institute and Stanford 3X Sanger Institute 5X TIGR 5X Sanger Institute 5X TIGR
– NS NS 15 562
– 10 682 NS NS
Plasmodium chabaudi AS Plasmodium berghei ANKA Plasmodium reichenowi Oscar Plasmodium gallinaceum A strain
3X 3X 3X 3X
NS 5337 NS NS
NS 5476 NS NS
Sanger Institute Sanger Institute Sanger Institute Sanger Institute
Number of Number of GSS Microarray projects EST in Gen in GenBank Bank dbESTb dbGSSb
Proteomic projects
cDNA arrays, gDNA arrays, Asexual stages, food oligo-arrays vacuole, sporozoite, gametocyte – – – – – – cDNA arrays, Asexual stages, oligo-arrays sporozoite, ookinete – – gDNA arrays – – – – –
aAbbreviations: 3X, threefold; 5X, fivefold; cDNA, complementary DNA; EST, expressed sequence tags from cDNA libraries; gDNA, genomic DNA; GSS, genome survey sequences from mung bean nuclease-digested genomic DNA libraries; NS, not significant; TIGR, The Institute for Genomic Research. bMany of the EST and GSS clones are available from the malaria repository, MR4, at http://www.malaria.mr4.org/mr4pages/index.html
http://parasites.trends.com
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Research Update
parasite proteins that protect against subsequent sporozoite challenge. Several presentations focused on antigenic variation in the rodent models. Genes from the P. yoelii and P. chabaudi genome data were identified as having high homology to the vir genes [8] in P. vivax (M. Turner, University of Glasgow, UK, and P. Preiser, National Institute for Medical Research, London, UK). Although the role of vir genes in antigenic variation is far from clear at this stage, the rodent malaria parasites seem to provide an ideal model system for the analysis of this complex phenotype. Perspective
Was the symposium a success? Undoubtedly so. Collaborations were forged and data swapped. A round table discussion identified key areas the community were interested in: (1) the availability of microarrays and facilities for their analysis, (2) more custom-orientated displays of the rodent malaria genome data alongside P. falciparum in PlasmoDB (Box 1f ), the repository and database for Plasmodium genomic data, and (3) the need for regular follow-on meetings
TRENDS in Parasitology Vol.18 No.3 March 2002
specifically devoted to efforts in model malaria parasite genome studies. Given the breadth of rodent malaria genomics and functional genomics efforts worldwide, the development of new tools and techniques for manipulating and studying nearly all stages of these parasites and the surge in genomic sequence data from projects under way, these parasites will undoubtedly form the foundation for the exploitation of malaria genome efforts. Acknowledgements
The organizers gratefully acknowledge the financial support of TIGR, National Institute of Allergy and Infectious Diseases, Burroughs Wellcome Fund grant 1003335 and Dept of Defense collaborative agreement DAMD17-98-2-8005 for sponsoring the symposium. The opinions expressed are those of the authors and do not reflect the official policy of the Dept of the Navy, Dept of Defense, or the US government. References 1 Gardner, M.J. (2001) A status report on the sequencing and annotation of the P. falciparum genome. Mol. Biochem. Parasitol. 118, 133–138
2 Landau, I. and Killick-Kendrick, R. (1966) Rodent plasmodia of the Republique Centrafricaine: the sporogony and tissue stages of Plasmodium chabaudi and P. berghei yoelii. Trans. R. Soc. Trop. Med. Hyg. 60, 633–649 3 Lander, E.S. et al. (2001) Initial sequencing and analysis of the human genome. Nature 409, 860–921 4 Venter, J.C. et al. (2001) The sequence of the human genome. Science 291, 1304–1351 5 Fortin, A. et al. (2001) Identification of a new malaria susceptibility locus (Char4) in recombinant congenic strains of mice. Proc. Natl. Acad. Sci. U. S. A. 95, 10793–10798 6 Lockhart, D.J. and Winzeler, E.A. (2000) Genomics, gene expression and DNA arrays. Nature 405, 827–836 7 Washburn, M.P. et al. (2001) Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat. Biotechnol. 19, 242–247 8 del Portillo, H.A. et al. (2001) A superfamily of variant genes encoded in the subtelomeric region of Plasmodium vivax. Nature 410, 839–842
Jane M. Carlton* Parasite Genomics Group, The Institute for Genomic Research, Rockville, MD 20850, USA. *e-mail: [email protected] Daniel J. Carucci Malaria Program, Naval Medical Research Center, Silver Spring, MD 20910, USA.
The Roy C. Anderson Memorial Lecture in Parasitology Starting in 2002, the University of Guelph, Ontario, Canada, will sponsor ‘The Roy C. Anderson Memorial Lecture in Parasitology’ annually. Parasitology is defined to include all aspects of microbial, protozoan and metazoan infections in animals and plants. An eminent scientist will be invited to deliver the lecture, to be on the campus and to interact with students and faculty members. The lecture series is to honour the late Professor Roy C. Anderson, who passed away unexpectedly on 26th August 2001. Roy had an outstanding research career; he had published >250 papers, and edited books, including the widely used CIH Keys to the Nematode Parasite of Vertebrates. He authored Nematode Parasites of Vertebrates: Their Development and Transmission (CAB International) and the second edition was published in 2000. He received several prestigious research awards including the Henry Baldwin Ward Medal, American Society of Parasitologists, Sigma Xi Award for Excellence in Research and, Robert Arnold Wardle Award, a Canadian Society of Zoologists. An endowment fund for the lecture series is being established and we solicit your financial support. Donations should be made payable to the ‘University of Guelph’ and sent to: Patrick T.K. Woo, Dept of Zoology, University of Guelph, Guelph, Ontario, Canada N1G 2W1. If you need more information on the lecture series, please contact Patrick T.K. Woo at [email protected]. We look forward to your support.
http://parasites.trends.com
1471-4922/02/$ – see front matter © 2002 Published by Elsevier Science Ltd. PII S1471-4922(02)02247-X
Research Update
Chemotherapy
Cryptosporidium is one of the few enteric protozoans for which no effective chemotherapy has been discovered (J.R. Mead, Emory University, Atlanta, GA, USA). The lack of adequate therapy puts humans and animals at risk when immune function is compromised. The lack of anti-cryptosporidial drugs could reflect the unique features of this parasite and include its cellular location and its phylogenetic affinities, which separate it from the coccidians. There is ample justification to evaluate new targets, novel classes of compounds and better ways of evaluating drug efficacy. In this respect, tubulin and tubulin-binding agents such as the dinitroanilines have potential (A. Armson, Murdoch University, Western Australia), and nitazoxanide could be a beneficial anticryptosporidial agent under certain circumstances (L. Favennec, Hospital Charles Nicolle, Rouen, France). Quantitative PCR procedures to evaluate drug efficacy in vitro have also been developed (L.M. MacDonald, Murdoch University, Western Australia). Synthesis
Closing discussions focused on nomenclature, taxonomy, establishing
TRENDS in Parasitology Vol.18 No.3 March 2002
databases, water industry needs, epidemiology and sources of infection, and directions for future research. There was general agreement that once Cryptosporidium genotypes were well characterized, it made sense to name them formally as distinct species. This has happened recently with Cryptosporidium canis and will now proceed for the human genotype (Type 1), Cryptosporidium hominis. It has been demonstrated that human infections with Type 1 and Type 2 isolates differ in their epidemiology: whether the clinical outcome also differs requires further investigation. However, although there was no resolution, the most controversial area is routine monitoring with respect to frequency and interpretation of results. Scientists might differ in their views but the final decision is driven by government legislation, and there is clearly insufficient data to convince some water authorities to lessen the stringency of their operations. The ability to genotype Cryptosporidium oocysts has provided a valuable epidemiological tool in studies on sources of infection and risk factors, which now needs to be expanded to include the exploration of sub-genotyping tools for epidemiological applications.
Cell culture, the oocyst structure, disinfection, chemotherapy, prophylaxis and molecular epidemiology were seen as the most important areas of future research. Acknowledgements
The Conference was generously supported by The Water Services Association of Australia, GlaxoSmithKline, The CRC for Water Quality and Treatment, American Water Works Association Research Foundation, Water Corporation of Western Australia, Australian Society for Microbiology and Murdoch University, Western Australia. The full proceedings from the conference will be published as a book Cryptosporidium: From Molecules to Disease edited by R.C.A. Thompson, A. Armson and U.M. Morgan-Ryan (Elsevier) during 2002. R.C. Andrew Thompson* Division of Veterinary and Biomedical Sciences, Murdoch University, Murdoch, Western Australia, 6150. *e-mail: [email protected] Rachel M. Chalmers Public Health Laboratory Service Cryptosporidium Reference Unit, Swansea PHL, Singleton Hospital, Swansea, UK SA2 8QA.
Rodent models of malaria in the genomics era Jane M. Carlton and Daniel J. Carucci The Rodent Malaria Genomics Symposium: Current Status and Future Directions was held on 15–16 November 2001 in Atlanta, GA, USA.
It has been apparent for the past few years in malaria research that basic biological knowledge of the rodent models of malaria lag far behind the very species they are intended to model. Why the study of the rodent malarias lags behind that of Plasmodium falciparum could partly be due to historical reasons and partly to a lack of acknowledgement concerning the usefulness of rodent model experimental data. Although direct extrapolation from rodent model biology to P. falciparum biology might not be applicable in all situations, each of the four rodent malaria species has similar characteristics to the four human malaria species, which http://parasites.trends.com
make them suitable for parallel study. For example, antigenic variation in Plasmodium chabaudi, in vivo drug testing with Plasmodium berghei, pre-erythrocytic stage vaccines with Plasmodium yoelii and chronobiology of Plasmodium vinckei. Following completion of the P. falciparum genome sequence and its imminent annotation and publication by the Malaria Genome Consortium [1], it would now seem an opportune time to pull together all available genomic information from diverse malaria species in an attempt to determine how these data can be used to develop better diagnostic tests, antimalarial drugs and vaccines. Current malaria genomics and proteomics studies
The Rodent Malaria Genomics symposium was opened by I. Landau (Natural History
Museum, Paris, France), who was the first to identify several African murine malaria species, including P. y. yoelii with R. Killick-Kendrick in 1966 [2]. From the basics of the rodent malaria life cycle, the symposium was brought sharply into the genomics era by presentations from three sequencing centers: The Institute for Genomic Research (TIGR), the Wellcome Trust Sanger Institute and Celera Genomics. A description of the P. yoelii genome sequencing project and simultaneous comparative genomics projects was given (J.M. Carlton, TIGR, Rockville, MD, USA). Approximately 3000 contigs with an average size of 7 kb are now available for this genome (see Box 1a) in addition to ~15 000 expressed sequence tags (ESTs) which represent the single largest EST dataset for a Plasmodium species (Box 1b). Comparative genomic
1471-4922/02/$ – see front matter © 2002 Published by Elsevier Science Ltd. PII: S1471-4922(01)02229-2
Research Update
TRENDS in Parasitology Vol.18 No.3 March 2002
101
Box 1. Websites of interest (a) The Institute for Genomic Research (TIGR) and Naval Medical Research Center Plasmodium yoelii genome sequencing program http://www.tigr.org/tdb/edb2/pya1/htmls/ (b) The TIGR Plasmodium yoelii gene index http://www.tigr.org/tdb/pygi/ (c) The Sanger Institute Plasmodium chabaudi partial genome shotgun project http://www.sanger.ac.uk/projects/p_chabaudi/ (d) The Sanger Institute Plasmodium berghei partial genome shotgun project http://www.sanger.ac.uk/projects/p_berghei/ (e) The Malaria Research and Reference Reagent Resource Center, MR4 http://www.malaria.mr4.org/mr4pages/index.html (f) The Plasmodium Genome Resource, PlasmoDB http://plasmodb.org
studies involving the creation of a global syntenic map between P. yoelii and P. falciparum are currently under way, which should aid the identification of orthologous genes between these species. This was followed by a description of the ongoing rodent malaria genome projects at the Sanger Institute Pathogen Sequencing Unit (N. Hall, Sanger Institute, Cambridge, UK). Partial shotgun sequencing of the P. chabaudi (Box 1c) and P. berghei (Box 1d) genomes to threefold coverage is expected to be available in the next few months, and a fivefold coverage of the primate malaria P. knowlesi has already finished. A discussion of the sevenfold mousegenome assembly generated from public and private sequencing efforts was also presented (R. Mural, Celera Genomics, Rockville, MD, USA). With the completion of a draft of the human genome [3,4], comparative genomics between mouse and human will enable direct correlations
between rodent malaria species (on a background of the host mouse genome), with human malaria species (on a background of the host human genome). To illustrate this, Mural chose a recent publication by one of the symposium attendees [5], which identified a mouse gene locus involved in host susceptibility to malaria. Synteny comparisons between the human and mouse genomes should now enable this and other loci to be mapped back to the human genome. Subsequent presentations were devoted to projects using the rodent malaria genome information in functional genomics projects. E. Winzeler (Scripps Research Institute, La Jolla, CA, USA) described an oligoarray chip consisting of 25-mers from genes of the P. falciparum and P. yoelii genomes, and the functional studies which could be done using these chips based on similar studies in yeast [6]. B. Bergman (MCP Hahnemann University, Philadelphia, PA, USA)
described the yeast two-hybrid studies and the cDNA microarray project under way in his lab, which uses 15 000 EST sequences and clones available for P. yoelii, recently submitted to GenBank dbEST (Table 1) and deposited with the Malaria Research and Reference Reagent Resource Center (MR4; Box 1e). L. Florens (Scripps Research Institute, CA, USA) outlined a high-throughput proteomic approach using MudPIT technology [7] to identify proteins from various stages of the P. yoelii life cycle, such as sporozoite, blood-stage and, soon, ookinete stages. Although supplies of these stages can be obtained from in vivo growth of the parasite, H. Hurd (University of Keele, UK) grabbed the attention of all participants by her elegant description of in vitro development of the P. berghei ookinete stage to infective sporozoite stage, without the need for development within the mosquito salivary glands. This means that the complete life cycle of P. berghei is now possible in vitro. Rodent malaria biology studies
The remainder of the symposium was put over to more biological presentations including immunology and vaccine studies, chemotherapy and drug resistance studies, and host–parasite biology. D. Haddad (Naval Medical Research Center, Silver Spring, MD, USA) gave an interesting presentation on using the open reading frames (ORFs) identified from P. yoelii genome data in high-throughput vaccinomic studies. Plasmid DNA from cloned ORFs are pooled and used as a DNA vaccine to immunize mice in an attempt to identify
Table 1. Plasmodium genome and functional genomics projectsa Species and line
Genome Project
Sequencing center
Plasmodium falciparum 3D7
6126
1782
P. falciparum patient isolate Plasmodium vivax Salvador I Plasmodium knowlesi H strain Plasmodium yoelii 17XNL
Whole TIGR, genome Sanger Institute and Stanford 3X Sanger Institute 5X TIGR 5X Sanger Institute 5X TIGR
– NS NS 15 562
– 10 682 NS NS
Plasmodium chabaudi AS Plasmodium berghei ANKA Plasmodium reichenowi Oscar Plasmodium gallinaceum A strain
3X 3X 3X 3X
NS 5337 NS NS
NS 5476 NS NS
Sanger Institute Sanger Institute Sanger Institute Sanger Institute
Number of Number of GSS Microarray projects EST in Gen in GenBank Bank dbESTb dbGSSb
Proteomic projects
cDNA arrays, gDNA arrays, Asexual stages, food oligo-arrays vacuole, sporozoite, gametocyte – – – – – – cDNA arrays, Asexual stages, oligo-arrays sporozoite, ookinete – – gDNA arrays – – – – –
aAbbreviations: 3X, threefold; 5X, fivefold; cDNA, complementary DNA; EST, expressed sequence tags from cDNA libraries; gDNA, genomic DNA; GSS, genome survey sequences from mung bean nuclease-digested genomic DNA libraries; NS, not significant; TIGR, The Institute for Genomic Research. bMany of the EST and GSS clones are available from the malaria repository, MR4, at http://www.malaria.mr4.org/mr4pages/index.html
http://parasites.trends.com
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Research Update
parasite proteins that protect against subsequent sporozoite challenge. Several presentations focused on antigenic variation in the rodent models. Genes from the P. yoelii and P. chabaudi genome data were identified as having high homology to the vir genes [8] in P. vivax (M. Turner, University of Glasgow, UK, and P. Preiser, National Institute for Medical Research, London, UK). Although the role of vir genes in antigenic variation is far from clear at this stage, the rodent malaria parasites seem to provide an ideal model system for the analysis of this complex phenotype. Perspective
Was the symposium a success? Undoubtedly so. Collaborations were forged and data swapped. A round table discussion identified key areas the community were interested in: (1) the availability of microarrays and facilities for their analysis, (2) more custom-orientated displays of the rodent malaria genome data alongside P. falciparum in PlasmoDB (Box 1f ), the repository and database for Plasmodium genomic data, and (3) the need for regular follow-on meetings
TRENDS in Parasitology Vol.18 No.3 March 2002
specifically devoted to efforts in model malaria parasite genome studies. Given the breadth of rodent malaria genomics and functional genomics efforts worldwide, the development of new tools and techniques for manipulating and studying nearly all stages of these parasites and the surge in genomic sequence data from projects under way, these parasites will undoubtedly form the foundation for the exploitation of malaria genome efforts. Acknowledgements
The organizers gratefully acknowledge the financial support of TIGR, National Institute of Allergy and Infectious Diseases, Burroughs Wellcome Fund grant 1003335 and Dept of Defense collaborative agreement DAMD17-98-2-8005 for sponsoring the symposium. The opinions expressed are those of the authors and do not reflect the official policy of the Dept of the Navy, Dept of Defense, or the US government. References 1 Gardner, M.J. (2001) A status report on the sequencing and annotation of the P. falciparum genome. Mol. Biochem. Parasitol. 118, 133–138
2 Landau, I. and Killick-Kendrick, R. (1966) Rodent plasmodia of the Republique Centrafricaine: the sporogony and tissue stages of Plasmodium chabaudi and P. berghei yoelii. Trans. R. Soc. Trop. Med. Hyg. 60, 633–649 3 Lander, E.S. et al. (2001) Initial sequencing and analysis of the human genome. Nature 409, 860–921 4 Venter, J.C. et al. (2001) The sequence of the human genome. Science 291, 1304–1351 5 Fortin, A. et al. (2001) Identification of a new malaria susceptibility locus (Char4) in recombinant congenic strains of mice. Proc. Natl. Acad. Sci. U. S. A. 95, 10793–10798 6 Lockhart, D.J. and Winzeler, E.A. (2000) Genomics, gene expression and DNA arrays. Nature 405, 827–836 7 Washburn, M.P. et al. (2001) Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat. Biotechnol. 19, 242–247 8 del Portillo, H.A. et al. (2001) A superfamily of variant genes encoded in the subtelomeric region of Plasmodium vivax. Nature 410, 839–842
Jane M. Carlton* Parasite Genomics Group, The Institute for Genomic Research, Rockville, MD 20850, USA. *e-mail: [email protected] Daniel J. Carucci Malaria Program, Naval Medical Research Center, Silver Spring, MD 20910, USA.
The Roy C. Anderson Memorial Lecture in Parasitology Starting in 2002, the University of Guelph, Ontario, Canada, will sponsor ‘The Roy C. Anderson Memorial Lecture in Parasitology’ annually. Parasitology is defined to include all aspects of microbial, protozoan and metazoan infections in animals and plants. An eminent scientist will be invited to deliver the lecture, to be on the campus and to interact with students and faculty members. The lecture series is to honour the late Professor Roy C. Anderson, who passed away unexpectedly on 26th August 2001. Roy had an outstanding research career; he had published >250 papers, and edited books, including the widely used CIH Keys to the Nematode Parasite of Vertebrates. He authored Nematode Parasites of Vertebrates: Their Development and Transmission (CAB International) and the second edition was published in 2000. He received several prestigious research awards including the Henry Baldwin Ward Medal, American Society of Parasitologists, Sigma Xi Award for Excellence in Research and, Robert Arnold Wardle Award, a Canadian Society of Zoologists. An endowment fund for the lecture series is being established and we solicit your financial support. Donations should be made payable to the ‘University of Guelph’ and sent to: Patrick T.K. Woo, Dept of Zoology, University of Guelph, Guelph, Ontario, Canada N1G 2W1. If you need more information on the lecture series, please contact Patrick T.K. Woo at [email protected]. We look forward to your support.
http://parasites.trends.com
1471-4922/02/$ – see front matter © 2002 Published by Elsevier Science Ltd. PII S1471-4922(02)02247-X