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Infection and Immunity cquired immunity2
Infection and Immunity Overview Malaria and Leishmaniasis are two parasitic diseases that infect more than 15% of humanity. Children are particularly vulnerable. Drug resistance to both diseases is increasing, so our goal is to improve methods of preventing and treating these diseases by understanding the parasite’s basic mechanisms of immunology, cell biology and genetics. The successful development of vaccines and novel chemotherapeutic treatments hinges on our deeper knowledge of these key determinants of the outcome of the relationship between the host and the invasive organism. Our ability to understand and affect disease outcomes in patients with malaria was greatly increased with the appointment of James Beeson, a public health physician and scientist with extensive experience in malarial countries such as Kenya and Malawi. Through a collaborative project with The National Institute for Malaria, Parasitology and Entomology (NIMPE) in Vietnam, our Division and Medicine at The University of Melbourne also provides expertise and staff training in laboratory protocols in Hanoi, and helps with field studies in several provinces. The project has achieved its first year goals and continues to provide valuable data on drug resistance, as well as strengthening NIMPE’s capacity for research and surveillance activities. Central to our activities is the identification of parasite proteins essential for the organism’s survival or pathogenesis in the host. These are possible drug targets. Analysis of GDP-Mannose Pyrophosphorylase (GDP-PM) from leishmania shows that deletion of the gene that encodes it results in an avirulent organism that does not cause disease in mice. Its expression and crystallisation is a first step towards the development of new anti-leishmanial treatments. Similarly for malaria, we have shown that the Serine-rich antigen (SERA) is not only essential for the parasite’s growth in human red blood cells but also that it is a protease. The expression of an active domain of this enzyme is a precursor to Research Focus development of inhibitors that lead to antimalarial drug development. To understand how the parasites cause disease in humans we must determine Functional genomics the events contributing to death in the case of malaria. We identified Pathogenesis of disease changes in the expression of 30,000 mouse genes after malarial infection. Distinct subsets of host genes are expressed differently due to infection Acquired immunity and this may underlie the development of malarial syndromes such as anemia, metabolic dysregulation and the inflammatory cascade. Parasite cell biology From left: Dr Louis Schofield, Dr Brendan Crabb, Dr Emanuela Handman, Dr James Beeson, Professor Alan Cowman (Head) 48 The Walter and Eliza Hall Institute of Medical Research Annual Report 2003 • 2004 Functional Genomics Position effect variegation and perinuclear compartmentalisation are linked to regulation of subtelomeric virulence genes in Plasmodium falciparum MT Duraisingh, TS Voss, AJ Marty, JK Thompson, RT Good, BS Crabb and AF Cowman, in collaboration with M Duffy (Medicine, The University of Melbourne) The malaria parasite Plasmodium falciparum undergoes antigenic consequently, as there could be up to seven chromosome ends variation to evade host responses through switching expression per cluster, this would bring a number of var genes within this of variant surface proteins encoded by the var gene family. domain. Even if only one chromosome end occupied the “active The var gene family is located in the subtelomeric regions of site”, because multiple var genes are often present on the one the 14 chromosomes. The overall structure of P falciparum end, it would be important to have additional tiers of regulation chromosome ends is highly conserved with distinct blocks of to ensure mutually exclusive expression and this is consistent repeated DNA defined as telomere associated repeat elements with maintenance of the silent state for the var gene adjacent (TAREs) 1 to 6 found immediately internal to the telomere to the active hDHFR locus. Current evidence suggests that var repeat tract. Subtelomeric var genes represent the most telomere- gene non-coding regions harbour important boundary elements proximal genes and are located directly downstream of TARE6, that may insulate them from derepressed chromatin in an active the largest block of repeat sequences. compartment of the nucleus. We have inserted a drug resistance gene cassette adjacent to a subtelomeric var in P falciparum and demonstrate reversible silencing of this gene by epigenetic mechanisms. Transcriptional activation of the integrated transgene is associated with increased sensitivity of local chromatin to nuclease digestion. When silenced, the inserted gene occupies a separate perinuclear location relative to a second episomally maintained marker of subtelomeric expression. However, when both genes are transcriptionally active they colocalise at the nuclear periphery. Using the same strategy we have shown that a specific subtelomeric var gene occupies distinct perinuclear positions depending on its state of activation. Together, this implies that perinuclear compartmentalisation and chromatin modification play an important role in the epigenetic regulation of subtelomeric virulence genes in P falciparum. Our data indicates that locus repositioning of subtelomeric var genes within the nucleus plays an important role in transcriptional regulation of this gene family and maintenance of monoallelic expression. Expression of a specific Figure 1. Fluorescent in situ hybridisation (FISH) analysis of P falciparum parasite chromosomes. The colours var gene would require its physical represent a chromosome end var2CSA and a plasmid pGEM. These only come together (bottom two rows) positioning within a nuclear domain when they are both expressed suggesting that there is a particular location in the nucleus that is permissive for competent for transcription and transcription. 49 Infection and Immunity Novel drugs against leishmaniasis target enzymes essential for mannose synthesis and glycosylation A Davis, L Kedzierski, A Hodder, J Stewart, B Smith, E Handman, in collaboration with M Perugini (Biochemistry and Molecular Biology, The University of Melbourne), T Ilg (Intervet Innovation GmbH, Schwabenheim, Germany) The current anti-Leishmania drugs, developed more than 50 As the first step in the elucidation of the three dimensional years ago, are difficult to administer, and toxic, and drug structure of the enzyme we have generated crystals and produced a resistance is on the rise. We aim to develop drugs to block two molecular model based on the structure of a bacterial homologue, enzymes in the mannose biosynthetic pathway, GDP-Mannose the N-acetyl-glucosamine-1-phosphate uridyltransferase Pyrophosphorylase (GDP-PM) and Phosphomannomutase (figure 2). Circular dichroism has revealed that it is comprised (PMM) which are essential for glycosylation in all eukaryotic of mixed α/β structures, in agreement with the model. We will organisms including Leishmania. Deletion of the two genes in use the three-dimensional structures and homology model of L mexicana produced avirulent organisms which were taken the enzyme for de novo ligand design and in silico screening of up by host macrophages but could not survive, suggesting that chemical databases. In parallel with the structural studies, we the inactivation of these enzymes should lead to cure. We have have developed enzyme assays suitable for high throughput produced recombinant GDP-MP and shown that its active screening of large chemical libraries of drug-like molecules. The form is a homo-hexamer that is stable at room temperature and two approaches should synergise to identify drug candidates and physiological pH. improve their functional specificity and efficacy. Figure 2. Three-dimensional model of the GDP-MP hexamer showing the view down the three-fold axis of the hexameric model. Molecular analysis of Plasmodium falciparum from resistance transporter (pfcrt, 76T) and multidrug resistance 1 drug treatment failure patients in Papua New (pfmdr1), were fixed in the population and two markers for Guinea pyrimethamine resistance, dihydrofolate reductase (dhps) 59R GJ Casey, AF Cowman, in collaboration with M Ginny, M Uranoli, and 108N, were found at moderate to high levels, overall 60% and I Mueller, JC Reeder (Papua New Guinea Institute of Medical 75%, respectively. No polymorphisms in dihydropteroate synthase Research), B Genton (Swiss Tropical Institute, Basel, Switzerland) (dhps), associated with sulfadoxine resistance, were present. These findings stress the need for regular monitoring of the effects of A study was conducted in Papua New Guinea to analyse Plasmodium standard drug treatment of uncomplicated malaria in Papua New falciparum drug resistance genes in patients with resistant malaria. Guinea. Two markers for 4-aminoquinoline resistance, chloroquine 50 The Walter and Eliza Hall Institute of Medical Research Annual Report 2003 • 2004 Pathogenesis of Disease Microarray analysis of the global transcriptional response during fatal malarial pathogenesis AC Sexton, RT Good, DS Hansen, L Buckingham, L Schofield, with K Simpson (Genetics and Bioinfomatics) The primary pathophysiological events contributing to malarial previously unknown transcriptional changes in the host that fatality are the cerebral syndrome, anaemia and metabolic may underlie the development of malarial syndromes such as acidosis. The molecular basis of each has been unclear. In this anaemia, metabolic dysregulation and the inflammatory cascade. study, microarray analysis of murine transcriptional responses Transcriptional profiling may therefore prove useful in elucidating during the development of severe disease revealed temporal, causal relationships in pathogenesis and immunity. Generation organ-specific and pathway-specific patterns. Of approximately of appropriate clinical samples and extension into other rodent 30,000 mouse genes, 99% have homologues in humans. We malarias will be important future steps in comparison of malarial observed only a small minority fluctuating transcriptionally in pathogenesis across host and parasite taxa. Microarray technology response to malarial insult. Over 400 genes in the brain and 600 therefore greatly extends the utility of rodent malarias as models in the spleen displayed transcriptional changes. The intensity for infection in humans. data for detectable transcripts from duplicate mice was very Figure 3. Overall results of microarray analyses of brains and spleens. A. strongly correlated (R2 = 0.99). Dominant patterns revealed Overall pattern of genes with changing transcript levels in brains (left panels) strongly suppressed erythropoiesis starting at early time-points and spleens (right panels) of infected C57BL/6 mice, compared with uninfected during infection, and highly up-regulated transcription of genes mice (day 0). Fold change is on the Y-axis and is plotted against time point (days controlling host glycolysis including lactate dehydrogenase. The 0, 1, 3, and 5) on the X-axis. Blue lines, transcripts increasing (top panels) or latter presents a mechanism that may contribute to metabolic decreasing (lower panels) on day 1 only; green lines, changes on day 3 only; red acidosis. No evidence for hypoxia-mediated regulation of these lines, changes on day 5 only; aqua lines, genes that changed on day 1 and day 3; yellow lines, genes that changed on day 3 and day 5; purple lines, genes that events was observed, raising the question of which transcriptional changed on day 1 and day 5; and white lines, genes that changed on all 3 days. pathway regulates expression of glycolytic enzymes in severe B. Venn diagrams showing numbers of transcripts that increased and decreased, malaria. Interferon-regulated gene transcripts dominated the respectively, at each time point in brains and spleens. Colour scheme is as above, inflammatory response to cytokines. These results demonstrate except that genes that changed at all 3 days are in black instead of white. 51 Infection and Immunity Dendritic cell populations in the Leishmania major A leucine rich repeat motif of Leishmania parasite infected skin and draining lymph nodes surface antigen-2 binds to macrophages through T Baldwin, J Curtis, E Handman, with M O’Keeffe, D Vremec, the complement receptor 3 with K Shortman (Immunology) L Kedzierski, J Montgomery, D Bullen, J Curtis, E Handman, in Using the metacyclic promastigotes-ear infection model of collaboration with E Gardiner (Monash University), A Jimenez- cutaneous leishmaniasis we showed that susceptible BALB/c Ruiz (University of Alcala, Madrid, Spain) mice have similar populations of dendritic cells, but an increased We studied the function of two Leishmania glycoconjugates, number of plasmacytoid dendritic cells in the draining lymph surface antigen-2 (PSA-2) and membrane proteophosphoglycan nodes compared to resistant C57BL/6 mice. The dendritic cells (PPG) and demonstrated that a series of Leucine Rich Repeats emigrating from the infected skin harboured no parasites, and (LRR) shared by PSA-2 and PPG bind to the mouse and the those in the lymph nodes did not harbour parasites until three human complement receptor 3 (CR3, Mac-1) in a calcium weeks after infection. In contrast, from very early in infection, a independent manner. This is the first demonstration of a significant percentage of macrophages emigrating from the skin functional role for PSA-2. Our data indicate that in addition to were infected indicating that they ferry the parasites to the lymph the two known ligands for host macrophages, leishmanolysin node where dendritic cells become infected. and lipophosphoglycan, parasite attachment and invasion of macrophages involves a third ligand comprising the LRRs shared by PSA-2 and PPG and that these interactions occur via the CR3. Acquired Immunity A specific type of functional antibodies can play a protective role against blood-stage Plasmodium falciparum infection in individuals in a malaria endemic area of Africa RA O’Donnell, TF de Koning-Ward, BS Crabb, in collaboration with CC John, AM Moormann, CL King, JW Kazura (Case Western Reserve University, Cleveland, OH USA), PO Sumba (Kenya Medical Research Institute, Kisian, Kenya) Recognition that individuals living in malaria endemic countries individuals were not all equally susceptible to re-infection with eventually become clinically immune to the disease has been a P falciparum following drug cure. Using a new neutralisation crucial factor driving the development of anti-malarial vaccines. assay developed recently by our group here at WEHI that is Surprisingly, however, the proteins that are targets of this based on use of transgenic P falciparum parasites, individuals clinical immunity remain poorly defined as do the mechanism with high-level MSP-119 specific invasion-inhibitory antibodies of action of protective antibodies. One malaria protein that has had a significantly reduced risk of blood-stage infection relative received considerable attention is the C-terminal fragment of to others in the population. In contrast, high levels of total Plasmodium falciparum merozoite surface protein 1 (MSP-119) MSP-119 antibodies as measured by enzyme immunoassay with – a protein that has now become a leading candidate for inclusion four different recombinant antigens did not correlate with in a human malaria vaccine. To examine the potential protective protection from infection. These findings implicate an important role of antibodies to MSP-119 in persons naturally exposed to protective role for MSP-119-specific invasion inhibitory antibodies malaria, we combined with our US and Kenyan collaborators in immunity to blood-stage P falciparum infection, and suggest to examine targets of immunity in a highland area of western that the measurement of MSP-119 specific inhibitory antibodies Kenya. A treatment time to infection study was performed may serve as an accurate correlate of protection in clinical trials over a 10-week period in 76 residents. These semi-immune of MSP-1-based vaccines. Figure 4. Neutralising but not total � � antibodies correlate with protection from re-infection with P falciparum malaria in ���� ���� a western Kenyan population. A. Time to P falciparum infection in individuals with ��������������������� high-level of total antibodies to MSP-119 ���� ���� measured (≥75th percentile) as compared to low-level total antibodies to PfMSP-119 ���� ���� (<75th percentile). B. Time to P falciparum infection in individuals with high-level �������������������������� �������������� ���� ���� neutralising antibodies (so called invasion- ������������������������� �������������� inhibitory antibodies or IIA) to MSP-119 (≥75th percentile) as compared to low-level ���� ���� IIA to MSP-119 (<75th percentile). Panel B � � � � � �� � � � � � �� shows that far fewer individuals became re- infected with malaria if they possessed high ��������������������������� levels of MSP-119 IIA at the time of drug clearance (time point 0). 52 The Walter and Eliza Hall Institute of Medical Research Annual Report 2003 • 2004 A common function for the double EGF-like receptor adaptor MyD88 were much more susceptible to infection modules of the highly divergent Plasmodium surface with L major than wild-types, demonstrating a central role for proteins this pathway in control of infection, and suggesting that L major DR Drew, RA O’Donnell, BS Crabb, with BJ Smith (Structural possesses a ligand for Toll-like receptors. LPG, but not other Biology) surface glycolipids, activated the innate immune system via TLR 2. Cytokine induction by LPG required the GPI anchor. LPG also In this study we addressed whether the diverse epidermal growth factor (EGF)-like domains that cover the surface of the human induced the expression of SOCS-1 and 3. Thus, Toll-like receptors malaria parasite P falciparum are capable of performing the same are required for resistance to L major and LPG is a Toll-like biological function. These domains, particularly those from receptor agonist from this protozoal pathogen. MSP-1, are amongst the leading vaccine candidates for the control CD1d-restricted NKT cells contribute to of blood-stage malaria. Our data shows that the MSP-1 EGF splenomegaly and enhance parasite-specific domains can be functionally complemented by radically different antibody responses in murine malaria EGF domains. One implication of this work is that this common DS Hansen, M-A Siomos, T de Koning-Ward, B Crabb, L EGF domain function may be targeted by intervention strategies. Buckingham, L Schofield In this regard we identified a highly conserved pocket that may be accessed by small molecule inhibitors. CD1d-restricted NKT cells contribute to malarial splenomegaly associated with expansion of the splenic B cell pool, and enhance MyD88 is essential for clearance of Leishmania parasite-specific antibody formation, in response to Plasmodium major: possible role for lipophosphoglycan and TLR2 berghei infection. The increased B cell responses correlate signalling with the ability of NKT cells to promote the development of MJ de Veer, JM Curtis, TM Baldwin, A Sexton, E Handman, TH2 immune responses. In addition, antibody against the GPI- L Schofield, in collaboration with JA DiDonato (The Lerner anchored protein Merozoite Surface Protein 1 (MSP-1) were Research Institute, Cleveland Clinic Foundation, Cleveland, OH found to be significantly lower in CD1–/– mice compared to wild- USA), MJ McConville (Biochemistry and Molecular Biology, The type animals. P berghei-infected MHCII–/– mice also generated University of Melbourne) antibodies against MSP-1, indicating that IgG production against Glycosylphosphatidylinositol (GPI)-anchored lipophosphoglycan GPI-anchored antigens can arise from both MHCII-dependent (LPG) is a virulence factor of Leishmania. Mice lacking the Toll and independent pathways during malaria infection. Life at WEHI. 53 Infection and Immunity Parasite Cell Biology Evidence that the unusual protease domain of Plasmodium falciparum SERA5 functions as an active enzyme AN Hodder, DR Drew, M Delorenzi, SK Miller, BS Crabb, with RJ Simpson (Joint ProteomicS Laboratory), TP Speed (Genetics and Bioinformatics), in collaboration with VC Epa (Health Sciences and Nutrition, CSIRO, Melbourne), R Bourgon (Statistics, University of California, CA USA), RL Moritz, DF Frecklington, RN Pike (Biochemistry and Molecular Biology, The University of Melbourne) A malaria antigen known as SERA5 has long been of considerable interest to malaria researchers because of its very strong expression, its apparent important role in blood-stage development and its potential as a vaccine and drug target. SERA5 has an unusual protease domain, which in most ways is typical of the cysteine protease papain family but oddly possesses a serine residue in the catalytic position. The prospect that this protein functions as a protease has been contentious. Our evidence that SERA5 retains catalytic activity provides impetus for the identification of inhibitors that may have potential as anti-malarial drugs. We also detail the evolutionary relationships of SERA family members and structurally model the protease domains. These data suggest that Plasmodium SERA proteases fall into two classes that are likely to have distinct biological roles. Figure 5. Molecular modelling reveals that SERA5 folds like a cysteine protease: Ribbon diagram the enzyme domains of SERA5 compared to caricain, a typical papain-family cysteine protease. The putative active site residues are depicted in stick form. In SERA5 these are appropriately positioned relative to one another in cleft. Selective inhibition of a two-step egress of malaria Plasmodium falciparum merozoite surface protein 6 parasites from the host erythrocyte is a dimorphic antigen ME Wickham, AF Cowman, in collaboration with JG Culvernor JA Pearce, T Triglia, AN Hodder, AF Cowman, in collaboration (Pathology, The University of Melbourne) with DC Jackson (Microbiology and Immunology, The University Escape from the host erythrocyte by the invading malaria of Melbourne), RF Anders (Biochemistry, La Trobe University) parasite is a fundamental step in the course of the disease about Merozoite surface protein 1 (MSP1) is implicated in the invasion of which little is known. Having developed into 16-32 daughter human erythrocytes by forming a complex with MSP6 and MSP7. merozoites within the parasitophorous vacuole, release from the MSP6 contains dimorphic elements in its protein structure. The erythrocyte involves a primary rupture of the parasitophorous sequences of eight MSP6 genes indicate that the alleles of each vacuole membrane, followed by a secondary rupture of the dimorphic form of MSP6 are highly conserved. 3D7-type MSP6 erythrocyte plasma membrane. Each step can be inhibited by alleles are detected in parasites from all malarious regions of the different protease inhibitors, implicating the involvement of world; K1-type MSP6 alleles have been detected in parasites from distinct proteases in each process. Our findings will facilitate SE Asia only. Cleavage of MSP6, which produces the p36 fragment the identification of the parasite and host molecules involved in in 3D7-type MSP6 and associates with MSP1, also occurs in K1- merozoite release. type MSP6 but at a different site in the protein. Anti-3D7 MSP6 antibodies weakly inhibited erythrocyte invasion by homologous 3D7 merozoites but did not inhibit a parasite line expressing the K1-type MSP6 allele. Antibodies from hyperimmune individuals affinity purified on an MSP3 peptide cross-reacted with MSP6; therefore, MSP6 may also be a target of antibody-dependent cellular inhibition. 54 The Walter and Eliza Hall Institute of Medical Research Annual Report 2003 • 2004 Strengthening malaria control and program capacity in Vietnam J Thompson, T Triglia, A Cowman, with S Thomas (Genetics and Bioinformatics), in collaboration with B Biggs, S Caruana (Medicine, The University of Melbourne), M Morris, B Hilton-Thorpe (Australian International Health Initiative), LD Cong, LK Thuan, NT Tien, NV Thanh (National Institute of Malariology, Parasitology and Entomology, Hanoi, Vietnam) We have instituted a joint program with the National Institute of Malariology, Parasitology and Entomology (NIMPE) in Hanoi, together with our colleagues at The University of Melbourne and the Australian International Health Initiative, to strengthen both research capacity and the ability to monitor drug resistance in Vietnam. In Vietnam, half the population live in forests and mountainous areas where they are at risk of malaria infection. In these remote areas, there is a significant unmet need for early and appropriate antimalarial therapy. Drug resistant malaria has been an increasing problem since the 1980s with levels of chloroquine resistance ranging from 41–62% and sulphadoxine- pyrimethamine resistance from 26–100%. Widespread usage of artemisinin and related drugs has resulted in reduced numbers of malaria cases since 1991 but has the potential to cause resistance and lead to a major malaria epidemic. Artesunate is widely available from local merchants and is often used indiscriminately Mr Nguyen Duc Giang, NIMPE, working in the newly-equipped Hanoi and in suboptimal dosage for the self-treatment of fever. laboratory, observed by Sonia Caruana, The University of Melbourne and Mr This program has been developing over the last year and resulted Troung van Hanh, NIMPE. in frequent visits from NIMPE scientists to this institute for both training and research to analyse the prevalence of drug resistance alleles in malaria parasites in Vietnam. This and other data analysed at NIMPE has provided important information on malarial drug resistance in the areas under study. The aim of this program is to use targeted field and laboratory-based analyses to assist in informing malaria drug use policies and practices that will, we hope, reduce morbidity and mortality. Ms Sonia Caruana with children from the Quang Tri District during a familiarisation visit in preparation for the Situational Analysis project in Quang Tri Province. Training Workshop at NIMPE for regional IMPE doctors. Ms Beth Hilton- Thorp, Australian International Health Initiative, with Dr Thanh Ngo and Mrs Pham Thi Xuyen, NIMPE. 55 Infection and Immunity Major Lectures and Exchanges Institute for Biotechnology, Sydney, 4/04, Speaker HHMI International Research Fellow Conference, Tallin, Estonia, 6/04, Speaker Alan Cowman Human Frontiers of Science Program Workshop, Marburg, Germany, 6/04, Biology of Parasitism 2003, Woods Hole, MA USA, 8/03, Lecturer Speaker ComBio 2003, Melbourne, 9/03, Session Chair Molecular Approaches to Malaria (MAM) 2004, Lorne, Victoria, 2/04, Speaker 2nd International Malaria Meeting, Hopkins Malaria Research Institute, Staff List Baltimore, MD USA, 3/04, Speaker Alan F Cowman, Division Head Washington University, School of Medicine, St Louis, MO USA, 3/04, Speaker Marian Cravino, Administrative Officer Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany, 5/04, Alan F Cowman, BSc(Hons) Griffith PhD Melb, Howard Hughes Speaker International Research Scholar Jacob Baum, BA(Hons) MA Oxon MSc PhD London WHO/TDR Symposium on “Social, economic and biological determinants Quang Phuc Bui, MD Hanoi, Visiting Scientist (from 10/03 to 12/03) of the emergence and spread of drug and insecticide resistance”, Accra, Tim-Wolf Gilberger, BBiology PhD Hamburg (to 8/03) Ghana, 6/04, Speaker Robert Good, BSc MSc(Prelim) Mon HHMI International Research Fellow Conference, Tallin, Estonia, 6/04, Julie Healer, BSc(Hons) Glasgow M Phil London PhD Edinburgh (from 7/03) Speaker Ellen Knuepfer, PhD Imperial College (to 2/04) Matthias Marti, MSc Basel PhD Zurich, Swiss National Science Foundation Brendan Crabb Fellow London School of Hygiene and Tropical Medicine, UK, 9/03, Speaker Melanie Rug, PhD Heidelberg ComBio 2003, Melbourne, 9/03, Speaker/Session chair Nicole Struck, BSc(Hons) Hamburg, Visiting Scientist (from 4/04 to 6/04) HHMI International Research Fellow Conference, Tallin, Estonia, 6/04, Till Voss, PhD Basel, Swiss National Science Foundation Fellow Speaker Gerard Casey, BSc(Hons) Mon Jennifer Thompson, BSc MSc Melb Emanuela Handman Tony Triglia, BSc(Hons) MSc Melb The Annual Scientific Meeting of the Australian Society for Parasitology, Darwin, 7/03, Speaker Christian Flueck, MSc Berne, Visiting Student (from 2/04) Jodi Thomson, BSc Wisconsin, Visiting Scientist (from 2/04 to 6/04) University of California, San Francisco CA USA, 6/04, Speaker Janine Stubbs, BSc Tas BSc(Hons) ANU, PhD Student Gordon Conference, Bristol, RI USA, 6/04, Speaker Malaria Functional Genomics Louis Schofield Alexander Maier, BSc Southern Colorado PhD Heidelberg Centenary Institute, Sydney, 7/03, Speaker Louisa McRobert, BSc Glasgow MSc Liverpool PhD Leeds, Visiting Scientist Human Frontiers of Science Program Workshop, Geneva, Switzerland, 9/03, (from 2/04 to 4/04) Speaker Monica Brown Matthew O’Neill, BSc(Hons) Melb CD1 Tetramer Workshop, NIAID, Bethesda, MD USA, 1/04, Speaker Brendan S Crabb, BSc(Hons) PhD Melb, Howard Hughes International British Society of Parasitology Autumn Symposium, UK, 3/04, Plenary Research Scholar Speaker Arlene Dent, BSc PhD MD Indiana, Visiting Scientist (from 2/04) New York University Vaccine Symposium, New York, NY USA, 3/04, Speaker Paul Gilson, BSc(Hons) PhD Melb ACKNOWLEDGMENTS Hazel and Pip Appel Fund EM Carty EM Newton Estate The Infection and Immunity PG Keir John PG Claridge Estate Jessie Reeves Estate Division acknowledges the Overseas: RAM del Cott Estate Agnes T Robertson Estate generous gifts and bequests listed Duncan Crawford Estate Stanley L Spencer Estate Human Frontier Science Program elsewhere in this Report and also SG Cubbins Estate Colin Syme Fellowship Fund Organization (France) thanks the following organisations, EJ (Ted) Darbyshire Estate John T Tomasetti Estate Howard Hughes Medical Institute trusts and persons whose major GC Graves Estate Tropical Diseases Fund (USA) grants supported research in this Joan Henderson Estate Dorothy Hope Walker Estate Atlantic Philanthropies Inc. Division. M Hamilton Estate Ita E Westcott Estate UNDP/World Bank/WHO Special Olive Maye Hemphill Estate Australia: Programme for Research and GAN Highton Estate National Health and Medical Training in Tropical Diseases EM Holmes Estate Research Council The Wellcome Trust (UK) Catherine M Jackson Estate Australian Research Council National Institutes of Health (USA) Alexia Lyell Bequest Fellowships Scheme Income from the following Funds Dr Ian Mackay Fellowship Fund Victorian State Government also supported this Division: Trevor Geoffrey Mansfield Estate Cooperative Research Centre for JW Ballantyne Estate GF Mitchell Fund Vaccine Technology Jean C Burns Estate Edith Moffatt Scholarship Fund Australian Agency for International Isabella A Brown Estate Ida Alice Moon Estate Development (AusAID) Catherine Carlson Estate Alan Ambrose Murray Estate 56 The Walter and Eliza Hall Institute of Medical Research Annual Report 2003 • 2004 Doron Greenbaum, BA PhD UCSF, Visiting Scientist (from 8/03) Staff Notes Tania de Koning-Ward, BSc(Hons) PhD Melb Damien Drew, BSc Mon BSc(Hons) PhD Melb, Peter Doherty Fellow Anthony Hodder, BSc(Hons) PhD Mon ARRIVALS Markus Meissner, PhD Heidelberg, Visiting Scientist (to 7/03) James Beeson, inaugural Miller Fellow from the Kenya Medical Research Institute, Kilifi, Kenya Soula Krejany, BSc MSc Melb Arlene Dent, Visiting Scientist from Rainbow Babies & Children’s Hospital, Rachel Lundie, BA/BSc(Hons) Melb, PhD Student Cleveland, OH USA Joanne McCoubrie, BSc(Hons) Murdoch, PhD Student (from 2/04) Allison Marty, BSc(Hons) Melb, Visiting PhD Student Christian Flueck, Visiting Scientist from the Swiss Tropical Institute, Basel, Susanne Miller, BSc(Hons) LaT, PhD Student Switzerland Paul Sanders, BSc(Hons) Melb, PhD Student Doron Greenbaum, Visiting Scientist from the University of California, San Danny Wilson, BSc(Hons) NTU, PhD Student (from 2/04) Francisco, CA USA James Beeson, BMedSc(Hons) MB BS(Hons) Mon PhD Melb, Miller Fellow Julie Healer, Research Officer from the Department of Medicine, The (from 6/04) University of Melbourne Emanuela Handman, MSc PhD Jerusalem Tony Davis, BSc(Hons) LaT PhD RMIT DEPARTURES Lukasz Kedzierski, BSc(Hons) PhD Mon, Peter Doherty Fellow Quang Phuc Bui, Visiting Scientist, returned to the NIMPE, Hanoi, Vietnam Beena Kumar, MB BS Madras MD Rohtak (to 1/04) Michael De Veer, Research Officer, to the Centre for Animal Biotechnology, Christiane Radt, MB BS Germany DTMH Lond Department of Medicine, The University of Melbourne Alex Uboldi, BSc(Hons) PhD Witwatersrand Tim-Wolf Gilberger, Research Officer, to the Bernhard Nocht Institute for Tracey Baldwin, BAppSc RMIT Tropical Medicine, Hamburg, Germany Joan Curtis Ellen Knuepfer, Research Officer, to the Division of Parasitology, National Mary Barson, BSc Melb, BSc(Hons) Student (from 2/04) Institute for Medical Research, UK Jim Stewart, BSc Melb, BSc(Hons) Student (to 4/04) Beena Kumar, Research Officer, to the Royal Children’s and Royal Women’s Louis Schofield, BSc MSc Lond PhD Qld, Howard Hughes International Hospitals, Melbourne Research Scholar Michael De Veer, PhD Mon (to 4/04) Louisa McRobert, Visiting Scientist, returned to the London School of Diana Hansen, BBiolSc Buenos Aires PhD Uppsala Hygiene & Tropical Medicine, UK Thomas Nebl, PhD LaT Markus Meissner, Visiting Scientist, returned to the Imperial College of Nicole Pettigrew, BAppSc(Hons) PhD RMIT (to 7/03) Science and Technology, London, UK Nicholas Bernard, BA/BSc(Hons) Melb Nicole Pettigrew, Research Officer, to the Royal Children’s Hospital, John Manzi, BSc(Hons) LaT (from 7/03) Melbourne Janet Steele, BAppSc RMIT (from 8/03) Mary-Anne Siomos, BBiolSc(Hons) LaT (to 9/03) Marta D’Ombrain, BSc(Hons) Melb , PhD Student (from 2/04) Krystal Evans, BSc(Hons) Wollongong, PhD Student Catherine Nie, BSc Melb, BSc(Hons) Student (from 2/04) New staff and students (from left): Christian Flueck, Janet Steele, Doron Greenbaum, James Beeson, Danny Wilson, Julie Healer, Quang Phuc Bui, Arlene Dent, John Manzi 57
"Infection and Immunity cquired immunity2"