My career has been devoted to studying how parasites and their hosts interact, with particular emphasis on immune responses to parasites and developing vaccines to fight parasitic disease. I received a PhD in Parasitology from the Australian National University in 1988 and from 1988 to 1990 was a National Research Fellow, also at the ANU.
I was then the Head of Coccidiosis Research in the Institute of Parasitology at the University of Zurich, Switzerland, until 1994, when I returned to Australia as a Queensland Institute of Medical Research Fellow.
I joined UTS as a Lecturer in 1996, was Acting Director of the Institute for the Biotechnology of Infectious Diseases in 2002 and its Deputy Director from 2003-2005. In 2005, I was appointed National Convenor of the ARC/NHMRC Research Network for Parasitology, an organisation charged with focusing and enhancing Australia's parasitological research effort.
I was appointed Professor of Parasitology at UTS in 2009, Tropical Leader and Professor of Cell Molecular Biology at James Cook University in 2011, Deputy Dean of Science and Health at Western Sydney University in 2017 and Discipline Leader of Biology and Biotechnology at UTS in 2018.
I was elected a Fellow of the Australian Society for Parasitology in 2008 in recognition of my service to parasitology research and education, awarded the Bancroft Mackerras Medal for research excellence in parasitology in 2018, and was elected a Member of the Order of Australia (AM) in 2019 for significant service to science as a parasitologist and immunologist, and to higher education.
I have been a Member of the Australian Society of Parasitology since 1985, a Fellow of the Society since 2008 and a Member of the Order of Australia since 2019.
Can supervise: YES
My research revolves around understanding how hosts and parasites interact with each other; this includes an interest in the immune response of hosts to parasites as well as adaptations of parasites that facilitate their survival, growth, reproduction, virulence and transmission. Ultimately, my research is directed at discovery of innovative ways to control parasitic diseases.
My research team applies a variety of techniques in biochemistry and proteomics, molecular biology and recombinant protein expression, cell culture, immunofluorescence microscopy, immunology and vaccinology.
I have been privileged to receive funding for my research from the National Health and Medical Research Council, the Australian Research Council, the Swiss Commission for Technology aand Innovation, the National Institutes of Health (USA), the Bellberry Foundation, the Swiss National Fund, the World Health Organisation and the Rural Industries Research and Development Corporation, funding that has been used to support numerous Honours, Masters and PhD students, as well as Postdoctoral Research Fellows.
I teach mainly parasitology and immunology, as well as contributing to a variety of other subjects in biomedical science, biotechnology and medical science degrees.
Ramakrishnan, C, Maier, S, Walker, RA, Rehrauer, H, Joekel, DE, Winiger, RR, Basso, WU, Grigg, ME, Hehl, AB, Deplazes, P & Smith, NC 2019, 'An experimental genetically attenuated live vaccine to prevent transmission of Toxoplasma gondii by cats.', Scientific reports, vol. 9, no. 1.View/Download from: Publisher's site
Almost any warm-blooded creature can be an intermediate host for Toxoplasma gondii. However, sexual reproduction of T. gondii occurs only in felids, wherein fertilisation of haploid macrogametes by haploid microgametes, results in diploid zygotes, around which a protective wall develops, forming unsporulated oocysts. Unsporulated oocysts are shed in the faeces of cats and meiosis gives rise to haploid sporozoites within the oocysts. These, now infectious, sporulated oocysts contaminate the environment as a source of infection for people and their livestock. RNA-Seq analysis of cat enteric stages of T. gondii uncovered genes expressed uniquely in microgametes and macrogametes. A CRISPR/Cas9 strategy was used to create a T. gondii strain that exhibits defective fertilisation, decreased fecundity and generates oocysts that fail to produce sporozoites. Inoculation of cats with this engineered parasite strain totally prevented oocyst excretion following infection with wild-type T. gondii, demonstrating that this mutant is an attenuated, live, transmission-blocking vaccine.
Alhallaf, R, Agha, Z, Miller, CM, Robertson, AAB, Sotillo, J, Croese, J, Cooper, MA, Masters, SL, Kupz, A, Smith, NC, Loukas, A & Giacomin, PR 2018, 'The NLRP3 Inflammasome Suppresses Protective Immunity to Gastrointestinal Helminth Infection.', Cell reports, vol. 23, no. 4, pp. 1085-1098.View/Download from: Publisher's site
Inflammasomes promote immunity to microbial pathogens by regulating the function of IL-1-family cytokines such as IL-18 and IL-1β. However, the roles for inflammasomes during parasitic helminth infections remain unclear. We demonstrate that mice and humans infected with gastrointestinal nematodes display increased IL-18 secretion, which in Trichuris-infected or worm antigen-treated mice and in macrophages co-cultured with Trichuris antigens or exosome-like vesicles was dependent on the NLRP3 inflammasome. NLRP3-deficient mice displayed reduced pro-inflammatory type 1 cytokine responses and augmented protective type 2 immunity, which was reversed by IL-18 administration. NLRP3-dependent suppression of immunity partially required CD4+ cells but was apparent even in Rag1-/- mice that lack adaptive immune cells, suggesting that NLRP3 influences both innate and adaptive immunity. These data highlight a role for NLRP3 in limiting protective immunity to helminths, suggesting that targeting the NLRP3 inflammasome may be an approach for limiting the disease burden associated with helminth infections.
Bussière, FI, Niepceron, A, Sausset, A, Esnault, E, Silvestre, A, Walker, RA, Smith, NC, Quéré, P & Laurent, F 2018, 'Establishment of an in vitro chicken epithelial cell line model to investigate Eimeria tenella gamete development.', Parasites & Vectors, vol. 11, no. 1, pp. 44-44.View/Download from: Publisher's site
Eimeria tenella infection leads to acute intestinal disorders responsible for important economic losses in poultry farming worldwide. The life-cycle of E. tenella is monoxenous with the chicken as the exclusive host; infection occurs in caecal epithelial cells. However, in vitro, the complete life-cycle of the parasite has only been propagated successfully in primary chicken kidney cells, which comprise undefined mixed cell populations; no cell line model has been able to consistently support the development of the sexual stages of the parasite. We therefore sought to develop a new model to study E. tenella gametogony in vitro using a recently characterised chicken cell line (CLEC-213) exhibiting an epithelial cell phenotype.CLEC-213 were infected with sporozoites from a precocious strain or with second generation merozoites (merozoites II) from wild type strains. Sexual stages of the parasite were determined both at the gene and protein levels.To our knowledge, we show for the first time in CLEC-213, that sporozoites from a precocious strain of E. tenella were able to develop to gametes, as verified by measuring gene expression and by using antibodies to a microgamete-specific protein (EtFOA1: flagellar outer arm protein 1) and a macrogamete-specific protein (EtGAM-56), but oocysts were not observed. However, both gametes and oocysts were observed when cells were infected with merozoites II from wild type strains, demonstrating that completion of the final steps of the parasite cycle is possible in CLEC-213 cells.The epithelial cell line CLEC-213 constitutes a useful avian tool for studying Eimeria epithelial cell interactions and the effect of drugs on E. tenella invasion, merogony and gametogony.
Lippuner, C, Ramakrishnan, C, Basso, WU, Schmid, MW, Okoniewski, M, Smith, NC, Hässig, M, Deplazes, P & Hehl, AB 2018, 'RNA-Seq analysis during the life cycle of Cryptosporidium parvum reveals significant differential gene expression between proliferating stages in the intestine and infectious sporozoites.', International journal for parasitology, vol. 48, no. 6, pp. 413-422.View/Download from: Publisher's site
Cryptosporidium parvum is a major cause of diarrhoea in humans and animals. There are no vaccines and few drugs available to control C. parvum. In this study, we used RNA-Seq to compare gene expression in sporozoites and intracellular stages of C. parvum to identify genes likely to be important for successful completion of the parasite's life cycle and, thereby, possible targets for drugs or vaccines. We identified 3774 protein-encoding transcripts in C. parvum. Applying a stringent cut-off of eight fold for determination of differential expression, we identified 173 genes (26 coding for predicted secreted proteins) upregulated in sporozoites. On the other hand, expression of 1259 genes was upregulated in intestinal stages (merozoites/gamonts) with a gene ontology enrichment for 63 biological processes and upregulation of 117 genes in 23 metabolic pathways. There was no clear stage specificity of expression of AP2-domain containing transcription factors, although sporozoites had a relatively small repertoire of these important regulators. Our RNA-Seq analysis revealed a new calcium-dependent protein kinase, bringing the total number of known calcium-dependent protein kinases (CDPKs) in C. parvum to 11. One of these, CDPK1, was expressed in all stages, strengthening the notion that it is a valid drug target. By comparing parasites grown in vivo (which produce bona fide thick-walled oocysts) and in vitro (which are arrested in sexual development prior to oocyst generation) we were able to confirm that genes encoding oocyst wall proteins are expressed in gametocytes and that the proteins are stockpiled rather than generated de novo in zygotes. RNA-Seq analysis of C. parvum revealed genes expressed in a stage-specific manner and others whose expression is required at all stages of development. The functional significance of these can now be addressed through recent advances in transgenics for C. parvum, and may lead to the identification of viable drug and vaccine ta...
Rajendran, E, Hapuarachchi, SV, Miller, CM, Fairweather, SJ, Cai, Y, Smith, NC, Cockburn, IA, Broer, S, Kirk, K & van Dooren, GG 2017, 'Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites', NATURE COMMUNICATIONS, vol. 8.View/Download from: Publisher's site
Ramakrishnan, C, Walker, RA, Eichenberger, RM, Hehl, AB & Smith, NC 2017, 'The merozoite-specific protein, TgGRA11B, identified as a component of the Toxoplasma gondii parasitophorous vacuole in a tachyzoite expression model.', International Journal for Parasitology, vol. 47, no. 10-11, pp. 597-600.View/Download from: Publisher's site
The apicomplexan, Toxoplasma gondii, infects all warm-blooded animals as intermediate hosts but only felids as definitive hosts. Dense granule proteins are critical for the survival of Toxoplasma within host cells but, whilst these proteins have been studied intensively in tachyzoites, little is known about their expression in the coccidian stages in the cat intestine. Transcriptomic profiling indicates that two putative dense granule proteins, TgGRA11A and TgGRA11B, are expressed uniquely in merozoites. Immunofluorescent microscopy of Toxoplasma-infected cat intestine and tachyzoites engineered to express TgGRA11B, reveals that it is a dense granule protein that traffics into the parasitophorous vacuole and its membrane.
Walker, RA, Niepceron, A, Ramakrishnan, C, Sedano, L, Hehl, AB, Brossier, F & Smith, NC 2016, 'Discovery of a tyrosine-rich sporocyst wall protein in Eimeria tenella', PARASITES & VECTORS, vol. 9.View/Download from: Publisher's site
Hehl, AB, Basso, WU, Lippuner, C, Ramakrishnan, C, Okoniewski, M, Walker, RA, Grigg, ME, Smith, NC & Deplazes, P 2015, 'Asexual expansion of Toxoplasma gondii merozoites is distinct from tachyzoites and entails expression of non-overlapping gene families to attach, invade, and replicate within feline enterocytes', BMC GENOMICS, vol. 16.View/Download from: Publisher's site
Miller, CM, Zakrzewski, AM, Robinson, DP, Fuller, SJ, Walker, RA, Ikin, RJ, Bao, SJ, Grigg, ME, Wiley, JS & Smith, NC 2015, 'Lack of a Functioning P2X7 Receptor Leads to Increased Susceptibility to Toxoplasmic Ileitis', PLOS ONE, vol. 10, no. 6.View/Download from: Publisher's site
Walker, RA, Sharman, PA, Miller, CM, Lippuner, C, Okoniewski, M, Eichenberger, RM, Ramakrishnan, C, Brossier, F, Deplazes, P, Hehl, AB & Smith, NC 2015, 'RNA Seq analysis of the Eimeria tenella gametocyte transcriptome reveals clues about the molecular basis for sexual reproduction and oocyst biogenesis', BMC GENOMICS, vol. 16.View/Download from: Publisher's site
Coccidiosis, a serious disease resulting from infection with parasitic protozoa of the genus Eimeria, causes significant economic losses to the poultry industry, where intensive rearing facilitates transmission of infectious oocysts via the fecal/oral route. Current control relies primarily on prophylactic drugs in feed but, whilst cost effective, the rise of drug resistance and public demands for residue-free meat has encouraged development of alternative control strategies. Chickens that recover from infection with Eimeria develop solid immunity that is directed against the early asexual stages of the parasite life cycle. This has allowed development of a number of vaccines that utilize deliberate infection with controlled doses of virulent oocysts or reproductively attenuated lines of Eimeria. The latter are immunogenic but non-pathogenic. The realization that both prophylactic drugs and attenuated vaccines control but do not eradicate infection with Eimeria encouraged development of a vaccine based upon maternal immunity. Laying hens exposed to Eimeria are able to transfer protective antibodies to hatchlings via egg yolks and these antibodies have been used to identify parasite proteins that are conserved across the genus. When delivered maternally, these provide an economical means of preventing coccidiosis, offering immediate protection to newly hatched chicks.
Chapman, HD, Barta, JR, Blake, D, Gruber, A, Jenkins, M, Smith, NC, Suo, X & Tomley, FM 2013, 'A Selective Review of Advances in Coccidiosis Research', ADVANCES IN PARASITOLOGY, VOL 83, vol. 83, pp. 93-171.View/Download from: Publisher's site
Rieux, A, Gras, S, Lecaille, F, Niepceron, A, Katrib, M, Smith, NC, Lalmanach, G & Brossier, F 2012, 'Eimeripain, a Cathepsin B-Like Cysteine Protease, Expressed throughout Sporulation of the Apicomplexan Parasite Eimeria tenella', PLoS One, vol. 7, no. 3, pp. 1-11.View/Download from: Publisher's site
The invasion and replication of Eimeria tenella in the chicken intestine is responsible for avian coccidiosis, a disease that has major economic impacts on poultry industries worldwide. E. tenella is transmitted to naïve animals via shed unsporulated oocysts that need contact with air and humidity to form the infectious sporulated oocysts, which contain the first invasive form of the parasite, the sporozoite. Cysteine proteases (CPs) are major virulence factors expressed by protozoa. In this study, we show that E. tenella expresses five transcriptionally regulated genes encoding one cathepsin L, one cathepsin B and three cathepsin Cs. Biot-LC-LVG-CHN2, a cystatin derived probe, tagged eight polypeptides in unsporulated oocysts but only one in sporulated oocysts. CP-dependant activities were found against the fluorescent substrates, Z-FR-AMC and Z-LR-AMC, throughout the sporulation process. These activities corresponded to a cathepsin B-like enzyme since they were inhibited by CA-074, a specific cathepsin B inhibitor
Katrib, M, Ikin, RJ, Brossier, F, Robinson, M, Slapetova, I, Sharman, PA, Walker, RA, Belli, SI, Tomley, FM & Smith, NC 2012, 'Stage-specific expression of protease genes in the apicomplexan parasite, Eimeria tenella', BMC GENOMICS, vol. 13.View/Download from: Publisher's site
Miller, CM, Boulter, NR, Fuller, SJ, Zakrzewski, AM, Lees, MP, Saunders, BM, Wiley, JS & Smith, NC 2011, 'The Role of the P2X(7) Receptor in Infectious Diseases', PLOS PATHOGENS, vol. 7, no. 11.View/Download from: Publisher's site
Lees, MP, Fuller, S, McLeod, R, Boulter, N, Miller, CM, Zakrzewski, AM, Mui, E, Witola, WH, Coyne, J, Hargrave, A, Jamieson, S, Blackwell, J, Wiley, JS & Smith, NC 2011, 'P2X7 receptor-mediated killing of an intracellular parasite, Toxoplasma gondii, by human and murine macrophages', Journal of Immunology, vol. 184, no. 12, pp. 7040-7046.View/Download from: Publisher's site
The P2X7R is highly expressed on the macrophage cell surface, and activation of infected cells by extracellular ATP has been shown to kill intracellular bacteria and parasites. Furthermore, single nucleotide polymorphisms that decrease receptor function reduce the ability of human macrophages to kill Mycobacterium tuberculosis and are associated with extrapulmonary tuberculosis. In this study, we show that macrophages from people with the 1513C (rs3751143, NM-002562.4:c.1487A>C) loss-of-function P2X 7R single nucleotide polymorphism are less effective in killing intracellular Toxoplasma gondii after exposure to ATP compared with macrophages from people with the 1513A wild-type allele. Supporting a P2X 7R-specific effect on T. gondii, macrophages from P2X7R knockout mice (P2X7R-/-) are unable to kill T. gondii as effectively as macrophages from wild-type mice. We show that P2X 7R-mediated T. gondii killing occurs in parallel with host cell apoptosis and is independent of NO production
Miller, CM, Zakrzewski, AM, Ikin, RJ, Boulter, N, Katrib, M, Lees, MP, Fuller, S, Wiley, JS & Smith, NF 2011, 'Dysregulation of the inflammatory response to the parasite, Toxoplasma gondii, in P2X7 receptor-deficient mice', International Journal For Parasitology, vol. 41, no. 3-4, pp. 301-308.View/Download from: Publisher's site
The P2X(7) receptor (P2X(7)R) is a two transmembrane receptor that is highly expressed on the surface of immune cells. Loss of function polymorphisms in this receptor have been linked to increased susceptibility to intracellular pathogens. P2X7R gene knockout (P2X(7)R(-/-); on a C57Bl/6J background), C57Bl/6J and BALB/c mice were infected with the avirulent ME49 strain of the intracellular parasite, Toxoplasma gondii. and susceptibility determined by monitoring weight loss. P2X7R(-/-) mice lost significantly more weight than C57Bl/6J mice from day 8 p.i. C57Bl/6J, in turn, lost significantly more weight than BALB/c mice. Thus, by day 10 p.i., P2X(7)R(-/-) mice had lost 5.7 +/- 0.7% of their weight versus 2.4 +/- 0.6% for C57Bl/6J mice, whereas BALB/c mice had gained 1.9 +/- 0.5%; by day 12 p.i., P2X(7)R(-/-) mice had lost 15.1 +/- 0.6%, C57Bl/6J had lost 10.1 +/- 0.8% and BALB/c had lost 4.8 +/- 0.8% of their weight. Neither parasite burden nor liver pathology was greater in the P2X(7)R(-/-) mice than in C57Bl/6J mice but BALB/c mice had significantly smaller numbers of parasites and less pathology in their livers than these strains. Absence of the P2X7 receptor did not affect IFN-gamma, IL-12, IL-1 beta, monocyte chemoattractant protein-1 (MCP-1) or TNF production. However, both P2X(7)R(-/-) and C57Bl/6J mice produced more IL-1 beta and INF than BALB/c mice. There was one important point of differentiation between the P2X(7)R(-/-) and C57Bl/6J mice, namely the significantly enhanced and prolonged production of nitric oxide, accompanied by delayed production of IL-10 in the P2X(7)R-deficient mice.
Mai, K, Smith, NC, Feng, Z, Katrib, M, Slapeta, J, Slapetova, I, Wallach, M, Luxford, C, Davies, MJ, Zhang, X, Norton, RS & Belli, SI 2011, 'Peroxidase catalysed cross-linking of an intrinsically unstructured protein via dityrosine bonds in the oocyst wall of the apicomplexan parasite, Eimeria maxima', International Journal For Parasitology, vol. 41, no. 11, pp. 1157-1164.View/Download from: Publisher's site
Apicomplexan parasites such as Eimeria maxima possess a resilient oocyst wall that protects them upon excretion in host faeces and in the outside world, allowing them to survive between hosts. The wall is formed from the contents of specialised organelles - wall-forming bodies - found in macrogametes of the parasites. The presence of dityrosine in the oocyst wall suggests that peroxidase-catalysed dityrosine cross-linking of tyrosine-rich proteins from wall-forming bodies forms a matrix that is a crucial component of oocyst walls. Bioinformatic analyses showed that one of these tyrosine-rich proteins, EmGAM56, is an intrinsically unstructured protein, dominated by random coil (52-70%), with some alpha-helix (28-43%) but a relatively low percentage of beta-sheet (1-11%); this was confirmed by nuclear magnetic resonance and circular dichroism. Furthermore, the structural integrity of EmGAM56 under extreme temperatures and pH indicated its disordered nature. The intrinsic lack of structure in EmGAM56 could facilitate its incorporation into the oocyst wall in two ways: first, intrinsically unstructured proteins are highly susceptible to proteolysis, explaining the several differently-sized oocyst wall proteins derived from EmGAM56; and, second, its flexibility could facilitate cross-linking between these tyrosine-rich derivatives. An in vitro cross-linking assay was developed using a recombinant 42 kDa truncation of EmGAM56. Peroxides, in combination with plant or fungal peroxidases, catalysed the rapid formation of dityrosine cross-linked polymers of the truncated EmGAM56, as determined by western blotting and HPLC, confirming this protein's propensity to form dityrosine bonds.
Parameswaran, N, Thompson, RS, Sundar, N, Pan, S, Johnson, MS, Smith, NC & Grigg, M 2010, 'Non-Archetypal Type Ii-Like And Atypical Strains Of Toxoplasma Gondii Infecting Marsupials Of Australia', International Journal For Parasitology, vol. 40, no. 6, pp. 635-640.View/Download from: Publisher's site
Australia is geographically isolated and possesses a remarkable diversity of wildlife species. Marsupials are highly susceptible to infection with the cosmopolitan parasite Toxoplasma gondii. Of 46 marsupials screened for T. gondii by multilocus PCR-DNA
Jamieson, S, Peixoto-rangel, A, Hargrave, A, De Roubaix, L, Mui, E, Boulter, N, Miller, E, Fuller, S, Wiley, JS, Castellucci, L, Boyer, K, Peixe, R, Kirisits, M, Elias, L, Coyne, J, Correa-oliveira, R, Sautter, M, Smith, NF, Lees, MP, Swisher, C, Heydemann, P, Noble, AG, Patel, D, Bardo, D, Burrowes, D, McLone, D, Roizen, N, Withers, S, Bahia-Oliveira, L, McLeod, R & Blackwell, J 2010, 'Evidence For Associations Between The Purinergic Receptor P2X(7) (P2Rx7) And Toxoplasmosis', Genes And Immunity, vol. 11, no. 5, pp. 374-383.View/Download from: Publisher's site
Congenital Toxoplasma gondii infection can result in intracranial calcification, hydrocephalus and retinochoroiditis. Acquired infection is commonly associated with ocular disease. Pathology is characterized by strong proinflammatory responses. Ligation of ATP by purinergic receptor P2X7, encoded by P2RX7, stimulates proinflammatory cytokines and can lead directly to killing of intracellular pathogens. To determine whether P2X7 has a role in susceptibility to congenital toxoplasmosis, we examined polymorphisms at P2RX7 in 149 child/parent trios from North America. We found association (FBAT Z-scores ±2.429; P=0.015) between the derived C(+)G(-) allele (f=0.68; OR=2.06; 95% CI: 1.143.75) at single-nucleotide polymorphism (SNP) rs1718119 (1068T>C; Thr-348-Ala), and a second synonymous variant rs1621388 in linkage disequilibrium with it, and clinical signs of disease per se. Analysis of clinical subgroups showed no association with hydrocephalus, with effect sizes for associations with retinal disease and brain calcifications enhanced (OR=3.04.25; 0.004
Walker, RA, Slapetova, I, Slapeta, J, Miller, CM & Smith, NC 2010, 'The Glycosylation Pathway Of Eimeria Tenella Is Upregulated During Gametocyte Development And May Play A Role In Oocyst Wall Formation', Eukaryotic Cell, vol. 9, no. 1, pp. 127-135.View/Download from: Publisher's site
Sexual-stage glycoproteins of Eimeria are important components of the oocyst wall, a structure that ensures the efficient transmission of these and related parasites. In this study, the primary enzyme in the glycosylation pathway of Eimeria tenella, gluc
Sharman, PA, Smith, NC, Wallach, M & Katrib, M 2010, 'Chasing the golden egg: Vaccination against poultry coccidiosis', Parasite Immunology, vol. 32, no. 8, pp. 590-598.View/Download from: Publisher's site
P>Eimeria species, of the Phylum Apicomplexa, cause the disease coccidiosis in poultry, resulting in severe economic losses every year. Transmission of the disease is via the faecal-oral route, and is facilitated by intensive rearing conditions in the poultry industry. Additionally, Eimeria has developed drug resistance against most anticoccidials used today, which, along with the public demand for chemical free meat, has lead to the requirement for an effective vaccine strategy. This review focuses on the history and current status of anticoccidial vaccines, and our work in developing the transmission-blocking vaccine, CoxAbic (R) (Netanya, Israel). The vaccine is composed of affinity-purified antigens from the wall-forming bodies of macrogametocytes of Eimeria maxima, which are proteolytically processed and cross-linked via tyrosine residues to form the environmentally resistant oocyst wall. The vaccine is delivered via maternal immunization, where vaccination of laying hens leads to protection of broiler offspring. It has been extensively tested for efficacy and safety in field trials conducted in five countries and involving over 60 million offspring chickens from immunized hens and is currently the only subunit vaccine against any protozoan parasite to reach the marketplace.
Miller, CM, Boulter, N, Ikin, RJ & Smith, NC 2009, 'The immunobiology of the innate response to Toxoplasma gondii', International Journal For Parasitology, vol. 39, no. 1, pp. 23-39.View/Download from: Publisher's site
Toxoplasma gondii is a unique intracellular parasite. It can infect a variety of cells in virtually all warm-blooded animals. It has a worldwide distribution and, overall, around one-third of people are seropositive for the parasite, with essentially the entire human population being at risk of infection. For most people, T. gondii causes asymptomatic infection but the parasite can cause serious disease in the immunocompromised and, if contracted for the first time during pregnancy, can cause spontaneous abortion or congenital defects, which have a substantial emotional, social and economic impact. Toxoplasma gondii provokes one of the most potent innate, pro-inflammatory responses of all infectious disease agents. It is also a supreme manipulator of the immune response so that innate immunity to T. gondii is a delicate balance between the parasite and its host involving a coordinated series of cellular interactions involving enterocytes, neutrophils, dendritic cells, macrophages and natural killer cells. Underpinning these interactions is the regulation of complex molecular reactions involving Toll-like receptors, activation of signalling pathways, cytokine production and activation of anti-microbial effector mechanisms including generation of reactive nitrogen and oxygen intermediates.
Miller, CM, Smith, NC, Ikin, RJ, Boulter, N, Dalton, JP & Donnelly, SM 2009, 'Immunological interactions between 2common pathogens, the Th1-inducing protozoan Toxoplasma gondii and the Th2-inducing helminth Fasciola hepatica', PLoS ONE, vol. 4, no. 5, pp. 1-10.
The nature of the immune response to infection is dependent on the type of infecting organism. Intracellular organisms such as Toxoplasma gondii stimulate a Th1-driven response associated with production of IL-12, IFN-?, nitric oxide and IgG2a antibodies and classical activation of macrophages. In contrast, extracellular helminths such as Fasciola hepatica induce Th2 responses characterised by the production of IL-4, IL-5, IL-10 and IgG1 antibodies and alternative activation of macrophages. As co-infections with these types of parasites commonly exist in the field it is relevant to examine how the various facets of the immune responses induced by each may influence or counter-regulate that of the other.
Miller, CMD, Smith, NC, Ikin, RJ, Boulter, NR, Dalton, JP & Donnelly, S 2009, 'Immunological interactions between 2 common pathogens, Th1-inducing protozoan Toxoplasma gondii and the Th2-inducing helminth Fasciola hepatica.', PloS one, vol. 4, no. 5, p. e5692.View/Download from: Publisher's site
BACKGROUND: The nature of the immune response to infection is dependent on the type of infecting organism. Intracellular organisms such as Toxoplasma gondii stimulate a Th1-driven response associated with production of IL-12, IFN-gamma, nitric oxide and IgG2a antibodies and classical activation of macrophages. In contrast, extracellular helminths such as Fasciola hepatica induce Th2 responses characterised by the production of IL-4, IL-5, IL-10 and IgG1 antibodies and alternative activation of macrophages. As co-infections with these types of parasites commonly exist in the field it is relevant to examine how the various facets of the immune responses induced by each may influence or counter-regulate that of the other. PRINCIPAL FINDINGS: Regardless, of whether F. hepatica infection preceded or succeeded T. gondii infection, there was little impact on the production of the Th1 cytokines IL-12, IFN-gamma or on the development of classically-activated macrophages induced by T. gondii. By contrast, the production of helminth-specific Th2 cytokines, such as IL-4 and IL-5, was suppressed by infection with T. gondii. Additionally, the recruitment and alternative activation of macrophages by F. hepatica was blocked or reversed by subsequent infection with T. gondii. The clinical symptoms of toxoplasmosis and the survival rate of infected mice were not significantly altered by the helminth. CONCLUSIONS: Despite previous studies showing that F. hepatica suppressed the classical activation of macrophages and the Th1-driven responses of mice to bystander microbial infection, as well as reduced their ability to reject these, here we found that the potent immune responses to T. gondii were capable of suppressing the responses to helminth infection. Clearly, the outcome of particular infections in polyparasitoses depends on the means and potency by which each pathogen controls the immune response.
Belli, SI, Ferguson, DJ, Katrib, M, Slapetova, I, Mai, K, Slapeta, J, Flowers, SA, Miska, KB, Tomley, FM, Shirley, M, Wallach, M & Smith, NC 2009, 'Conservation of proteins involved in oocyst wall formation in Eimeria maxima, Eimeria tenella and Eimeria acervulina', International Journal For Parasitology, vol. 39, no. 10, pp. 1063-1070.View/Download from: Publisher's site
Vaccination with proteins from gametocytes of Eimeria maxima protects chickens, via transfer of maternal antibodies, against infection with several species of Eimeria. Antibodies to E. maxima gametocyte proteins recognise proteins in the wall forming bodies of macrogametocytes and oocyst walls of E. maxima, Eimeria tenella and Eimeria acervulina. Homologous genes for two major gametocyte proteins GAM56 and GAM82 were found in E. maxima, E. tenella and E. acervulina. Alignment of the predicted protein sequences of these genes reveals that, as well as sharing regions of tyrosine richness, strong homology exists in their amino-terminal regions, where protective antibodies bind. This study confirms the conservation of the roles of GAM56 and GAM82 in oocyst wall formation and shows that antibodies to gametocyte antigens of E. maxima cross-react with homologous proteins in other species, helping to explain cross-species maternal immunity.
Mai, K, Sharman, PA, Walker, RA, Katrib, M, De Souza, D, McConville, M, Wallach, M, Belli, SI, Ferguson, DJ & Smith, NC 2009, 'Oocyst wall formation and composition in coccidian parasites', Memorias do Instituto Oswaldo Cruz, vol. 104, no. 2, pp. 281-289.
The oocyst wall of coccidian parasites is a robust structure that is resistant to a variety of environmental and chemical insults. This resilience allows oocysts to survive for long periods, facilitating transmission from host to host. The wall is bilayered and is formed by the sequential release of the contents of two specialized organelles - wall forming body 1 and wall forming body 2 - found in the macrogametocyte stage of Coccidia. The oocyst wall is over 90% protein but few of these proteins have been studied. One group is cysteine-rich and may be presumed to crosslink via disulphide bridges, though this is yet to be investigated. Another group of wall proteins is rich in tyrosine. These proteins, which range in size from 8-31 kDa, are derived from larger precursors of 56 and 82 kDa found in the wall forming bodies. Proteases may catalyze processing of the precursors into tyrosine-rich peptides, which are then oxidatively crosslinked in a reaction catalyzed by peroxidases. In support of this hypothesis, the oocyst wall has high levels of dityrosine bonds. These dityrosine crosslinked proteins may provide a structural matrix for assembly of the oocyst wall and contribute to its resilience.
Wallach, M, Ashash, U, Michael, A & Smith, NC 2008, 'Field application of a subunit vaccine against an enteric protozoan disease', PLoS ONE, vol. 3, no. 12, pp. 1-7.View/Download from: Publisher's site
A subunit vaccine composed of purified antigens from the gametocytes of Eimeria maxima was used to stimulate the production and transfer of maternal antibodies between breeding hens and their hatchlings. The vaccine was injected into hens twice before they began laying eggs. Immunization had no adverse affects on egg laying or health of the hens and resulted in high antibody levels throughout the life of the hens. Progeny of immunized hens excreted significantly less oocysts of various species of Eimeria in their faeces than chicks from unvaccinated hens. Furthermore, the offspring of vaccinated hens developed stronger natural immunity to Eimeria, so that they were resistant to challenge infection even at 8 weeks of age, well after all maternal antibodies had left their circulation. Field trials were conducted in South Africa, Brazil and Thailand, involving at least 1 million progeny of vaccinated hens and at least 1 million positive control birds (raised on feed containing anticoccidial drugs or immunized with a live vaccine) in each country. Additionally, trials were carried out in Israel involving 60 million progeny of vaccinated hens and 112 million positive control birds. There were no significant differences in growth rate, feed conversion ratios or mortality in the offspring of vaccinated hens compared with the positive control chickens in any of these countries regardless of different management practices, different breeds of chickens or climate.
Mello, F, Alvarez, R, Smith, NC & Michael, A 2006, 'A novel approach to coccidiosis control', International Hatchery Practice, vol. 20, no. NA, pp. 7-13.
Smith, NC, Tilley, L, Thompson, RS, Ryan, UM, Loukas, AC, Jenkins, D & McFadden, GI 2006, 'An Australian network to support the understanding and control of parasites', Trends In Parasitology, vol. 22, no. 3, pp. 97-99.
The Australian Research Council (ARC) and the National Health and Medical Research Council (NHMRC) Research Network for Parasitology will focus and coordinate the fundamental, strategic and applied parasitology research in Australia. It will raise the st
Coccidian parasites are transmitted between hosts by the ingestion of food or water contaminated with oocysts, followed by the release of infectious sporozoites and invasion of the gastro-intestinal tract. In the external environment, sporozoites are pro
Belli, SI, Mai, K, Skene, C, Gleeson, M, Witcombe, DM, Katrib, M, Finger, A, Wallach, M & Smith, NC 2004, 'Characterisation of the antigenic and immunogenetic properties of bacterially expressed, sexual stage antigens of the coccidian parasite, Eimeria maxima', Vaccine, vol. 22, pp. 4316-4325.View/Download from: Publisher's site
Witcombe, DM, Ferguson, DJ, Belli, SI, Wallach, M & Smith, NC 2004, 'Eimeria maxima TRAP family protein EmTFP250: subcellular localisation and induction of immune responses by immunisation with a recombinant C-terminal derivative', International Journal for Parasitology, vol. 34, pp. 861-872.View/Download from: Publisher's site
Belli, S, Wallach, M, Luxford, C, Davies, MJ & Smith, NC 2003, 'Roles of tyrosine-rich precursor glycoproteins and dityrosine-/DOPA-mediated protein crosslinking in oocyst wall assembly in the coccidian parasite, Eimeria maxima', Eukaryotic Cell, vol. 2, no. 3, pp. 456-464.View/Download from: Publisher's site
The oocyst wall of apicomplexan parasites protects them from the harsh external environment, preserving their survival prior to transmission to the next host. If oocyst wall formation could be disrupted, then logically, the cycle of disease transmission could be stopped, and strategies to control infection by several organisms of medical and veterinary importance such as Eimeria, Plasmodium, Toxoplasma, Cyclospora, and Neospora could be developed. Here, we show that two tyrosine-rich precursor glycoproteins, gam56 and gam82, found in specialized organelles (wall-forming bodies) in the sexual stage (macrogamete) of Eimeria maxima are proteolytically processed into smaller glycoproteins, which are then incorporated into the developing oocyst wall. The identification of high concentrations of dityrosine and 3,4-dihydroxyphenylalanine (DOPA) in oocyst extracts by high-pressure liquid chromatography, together with the detection of a UV autofluorescence in intact oocysts, implicates dityrosine- and possibly DOPA-protein cross-links in oocyst wall hardening. In addition, the identification of peroxidase activity in the wall-forming bodies of macrogametes supports the hypothesis that dityrosine- and DOPA-mediated cross-linking might be an enzyme-catalyzed event. As such, the mechanism of oocyst wall formation in Eimeria, is analogous to the underlying mechanisms involved in the stabilization of extracellular matrices in a number of organisms, widely distributed in nature, including insect
Belli, SI, Wallach, M & Smith, NC 2003, 'Cloning and characterization of the 82 kDa tyrosine-rich sexual stage glycoprotein, GAM82, and its role in oocyst wall formation in the apicomplexan parasite, Eimeria maxima', Gene, vol. 307, pp. 201-212.View/Download from: Publisher's site
Belli, SI, Wallach, M, Luxford, C, Davies, MJ & Smith, NC 2003, 'Roles of tyrosine-rich precursor glycoproteins and dityrosine- and 3,4-dihydroxyphenylalanine-mediated protein cross-linking in development of the oocyst wall in the coccidian parasite Eimeria maxima', Eukaryotic Cell, vol. 2, no. 3, pp. 456-464.View/Download from: Publisher's site
Ferguson, DJ, Belli, SI, Smith, NC & Wallach, M 2003, 'The development of the macrogamete and oocyst wall in Eimeria maxima: immuno-light and electron microscopy', International Journal For Parasitology, vol. 33, no. 12, pp. 1329-1340.View/Download from: Publisher's site
Witcombe, DM, Belli, SI, Wallach, M & Smith, NC 2003, 'Molecular characterisation of EmTFP250: a novel member of the TRAP protein family in Eimeria maxima', International Journal For Parasitology, vol. 33, no. 7, pp. 691-702.View/Download from: Publisher's site
Dobbin, CA, Smith, NC & Johnson, AM 2002, 'Heat shock protein 70 is a potential virulence factor in murine Toxoplasma infection via immunomodulation of host NF-kappa B and nitric oxide', JOURNAL OF IMMUNOLOGY, vol. 169, no. 2, pp. 958-965.View/Download from: Publisher's site
Dobbin, CA, Smith, NC & Johnson, AM 2002, 'Heat shock protein 70 is a virulence factor in murine Toxoplasma infection via immunomodulation of host nuclear factor kappa B and nitic oxide', Journal of Immunology, vol. 169, no. N/A, pp. 958-965.
Belli, SI, Bakar, M, Thebo, P, Wallach, M, Schwartsburd, B & Smith, NC 2002, 'Biochemical characterisation of the 56 and 82 kDa immunodominant gametocyte antigens from Eimeria maxima', International Journal for Parasitology, vol. 32, no. N/A, pp. 805-816.
Belli, SI, Witcombe, DM, Wallach, M & Smith, NC 2002, 'Functional genomics of gam56: role of a 56 kilodation sexual stage antigen in oocyst wall formation in Eimeria maxima', International Journal for Parasitology, vol. 32, no. N/A, pp. 1727-1737.View/Download from: Publisher's site
Miller, CM, Soilemezis, C, Johnson, AM & Smith, NC 2000, 'The Production of a 70 kDa Heat Shock Protein by Toxoplasma gondii RH Strain in Immunocompromised Mice', International Journal for Parasitology, vol. 30, no. 0, pp. 1467-1473.
Miller, CM, Smith, NC & Johnson, AM 1999, 'Cytokines, Nitric Oxide, Heat Shock Proteins And Virulence In Toxoplasma', Parasitology Today, vol. 15, no. 10, pp. 418-422.View/Download from: Publisher's site
Elucidating the factors that play important roles in the expression of virulence by parasites is crucial to understanding disease pathogenesis and to developing control strategies rationally. Here, Kate Miller, Nick Smith and Alan Johnson, using Toxoplas
Fell, A & Smith, NC 1998, 'Immunity to asexual blood stages of Plasmodium: is resistance to acute malaria adaptive or innate?', Parasitology Today, vol. 14, no. 9, pp. 364-369.View/Download from: Publisher's site
Current models of immunity to blood stages of Plasmodium invoke a primary role for T-cell dependent processes and much recent evidence implicates Th1-type responses as crucial to the control of acute malaria. But do these data stand up to close scrutiny? Here, Andy Fell and Nick Smith review recent data from rodent and human studies and suggest that Th1-type responses may not after all be important in controlling malaria infection in the blood.
Smith, NC, Favila-Castillo, L, Monroy-Ostria, A, Hirunpetcharat, C & Good, MF 1997, 'The spleen, IgG antibody subsets and immunity to Plasmodium berghei in rats', Immunology And Cell Biology, vol. 75, no. 3, pp. 318-323.View/Download from: Publisher's site
The development of IgG subclass-specific antibody responses to Plasmodium berghei in spleen-chimeric rats were monitored to determine if there was any relationship between IgG subset profiles and resistance. Strongly immune eusplenic rats respond to challenge with P. berghei by producing high levels of parasite-specific IgG2a, IgG2b and IgG2c but only modest levels of IgG1. Splenectomy profoundly affects the antibody response to infection. Thus, in splenectomized immunized rats, which harbour a chronic parasitaemia of 1%, the IgG2a, IgG2b and IgG2c responses peak 1 week later than in eusplenic immunized rats although the size of the peak is similar. More marked effects are apparent in the IgG1 response, the magnitude of which is far greater in splenectomized immunized rats than eusplenic immunized rats. Similar antibody profiles are seen in splenectomized immunized rats transplanted with a naive spleen. In contrast, splenectomized naive rats receiving either a transplant of a spleen from an immune rat or a transfer of immune spleen cells have high levels of IgG2a, IgG2b and IgG2c but modest levels of IgG1. However, only the former group of rats completely clears the parasite, the latter maintaining a chronic 1% parasitaemia. Thus, although complete resistance to P. berghei is always associated with high levels of parasite-specific IgG2a, IgG2b and IgG2c plus modest levels of IgG1, this is not a sufficient set of conditions to guarantee complete immunity. The IgG subset profile may be related to cytokine production; IFN-gamma was detected in the sera of rats receiving spleens from rats immune to P. berghei (modest IgG1 responses) but not in rats receiving spleens from naive animals (pronounced IgG1 responses).
Smith, NC & Ovington, K 1996, 'The effect of BCG, zymosan and Coxiella biirnetti extract on Eimeria infections', Immunology And Cell Biology, vol. 74, no. NA, pp. 346-348.
Smith, NC & Ovington, K 1996, 'The Effect Of Bcg, Zymosan And Coxiella Burnetti Extract On Eimeria Infections', Immunology And Cell Biology, vol. 74, no. 4, pp. 346-348.View/Download from: Publisher's site
Infection of animals with species of Eimeria induces a hyper-reactivity to endotoxin as manifest by a greatly increased capacity of infected animals to produce TNF in response to LPS in vivo compared with uninfected animals. This finding indicates primin
Deplazes, P, Smith, NC, Arnold, P, Lutz, H & Eckert, J 1995, 'Specific IGG1 And IGG2 Antibody-responses Of Dogs To Leishmania-infantum And Other Parasites', Parasite Immunology, vol. 17, no. 9, pp. 451-458.View/Download from: Publisher's site
Sera from dogs naturally infected with Leishmania infantum were analysed for the IgG subclass specificity of their antibody response by ELISA. Dogs infected with L. infantum produced both IgG1 and IgG2 antibodies with IgG2 being associated with asymptoma
Smith, NC, Ovington, K, Deplazes, P & Eckert, J 1995, 'Cytokine And Immunoglobulin Subclass Responses Of Rats To Infection With Eimeria-nieschulzi', Parasitology, vol. 111, pp. 51-57.View/Download from: Publisher's site
SIV rats infected with a high dose (50000 oocysts) of Eimeria nieschulzi displayed clinical symptoms of coccidiosis such as diarrhoea (days 6 and 7 post-primary infection) and weight loss (days 6-8 post-primary infection) and were completely immune to ch
Smith, NC, Ovington, KS, Deplazes, P & Eckert, J 1995, 'Cytokine and immunoglobulin subclass responses of rats to infection with Eimeria nieschulzi', Parasitology, vol. 111, no. 1, pp. 51-57.
SIV rats infected with a high dose (50000 oocysts) of Eimeria nieschulzi displayed clinical symptoms of coccidiosis such as diarrhoea (days 6 and 7 post-primary infection) and weight loss (days 6-8 post-primary infection) and were completely immune to challenge with a similar dose. The ability of rats to produce tumour necrosis factor (TNF) in vivo was enhanced during the period of oocyst excretion in the primary infection but significant production of TNF did not occur after challenge infection. Thus, TNF does not appear to be an important factor in resistance to infection with E. nieschulzi but may play some role in resistance to primary infection and in the pathology associated with E. nieschulzi infection. Parasite-specific serum IgM levels (measured by enzyme-linked immunosorbent assay) were also increased during primary infection but returned to background levels at the end of the patent period and were not affected by challenge infection. In contrast to TNF and IgM, serum concentrations of E. nieschulzi-specific IgG1, IgG2a, IgG2b, IgG2c and intestinal tissue levels of IgA did not begin to increase until after day 12 post-primary infection, reached peak levels between days 20 and 30 post-primary infection and were slightly increased by challenge infection.
Wallach, M, Smith, NC, Braun, R & Eckert, J 1995, 'Potential Control Of Chicken Coccidiosis By Maternal Immunization', Parasitology Today, vol. 11, no. 7, pp. 262-265.View/Download from: Publisher's site
The control of coccidiosis by maternal immunization represents on important potential strategy in the fight against this serious veterinary health problem. In this short review, Michael Wallach, Nicholas Smith, Richard Braun and Johannes Eckert present a
Wallach, M, Smith, NC, Petracca, M, Miller, CM, Eckert, J & Braun, R 1995, 'Eimeria-maxima Gametocyte Antigens - Potential Use In A Subunit Maternal Vaccine Against Coccidiosis In Chickens', Vaccine, vol. 13, no. 4, pp. 347-354.View/Download from: Publisher's site
Affinity-purified gametocyte antigens (APGA) from Eimeria maxima, emulsified in Freunds adjuvant, were injected intramuscularly into breeding hens on two or three occasions, As a result, progeny of the immunized hens were partially immune to infection wi
Roditi, I, Wyler, T, Smith, NC & Braun, R 1994, 'Virus-like particles in Eimeria nieschulzi are associated with multiple RNA segments', Molecular And Biochemical Parasitology, vol. 63, no. NA, pp. 275-282.
Smith, NC & Ovington, K 1994, 'Nippostrongylus-brasiliensis - Ability Of Plasma To Prime Free-radical Generation By Leukocytes In Response To Adult Worms Not Due To Gamma-interferon Or Tumor Necrosis', International Journal For Parasitology, vol. 24, no. 7, pp. 959-966.View/Download from: Publisher's site
Plasma-borne factors prime leukocytes from both infected and uninfected rats for radical generation in response to N. brasiliensis. The concentration of these factors is increased following infection and reaches maximal levels on day 8 post-infection (p.
Smith, NC, Hunt, M, Ellenrieder, C, Eckert, J & Shirley, M 1994, 'Detection Of Metabolic Enzymes Of Eimeria By Ampholine-polyacrylamide Gel Isoelectricfocusing', Parasitology Research, vol. 80, no. 2, pp. 165-169.View/Download from: Publisher's site
Smith, NC, Wallach, M, Miller, CM, Morgenstern, R, Braun, R & Eckert, J 1994, 'Maternal Transmission Of Immunity To Eimeria-maxima - Enzyme-linked-immunosorbent-assay Analysis Of Protective Antibodies Induced By Infection', Infection And Immunity, vol. 62, no. 4, pp. 1348-1357.
Vaccination of broiler chickens against Eimeria infection is problematic because of the need to ensure that birds are protected from the time of hatching. We have therefore investigated the feasibility of protecting hatchling broilers via maternal transf
SMITH, NC, WALLACH, M, MILLER, CMD, BRAUN, R & ECKERT, J 1994, 'MATERNAL TRANSMISSION OF IMMUNITY TO EIMERIA-MAXIMA - WESTERN-BLOT-ANALYSIS OF PROTECTIVE ANTIBODIES INDUCED BY INFECTION', INFECTION AND IMMUNITY, vol. 62, no. 11, pp. 4811-4817.View/Download from: Publisher's site
Smith, NC, Wallach, M, Petracca, M, Braun, R & Eckert, J 1994, 'Maternal Transfer Of Antibodies Induced By Infection With Eimeria-maxima Partially Protects Chickens Against Challenge With Eimeria-tenella', Parasitology, vol. 109, pp. 551-557.View/Download from: Publisher's site
Infection of breeding hens with Eimeria maxima induces production of Eimeria-specific IgG antibodies which are transferred to hatchlings via the egg yolk and confer a high degree of maternal immunity against homologous challenge and partial immunity to i
Wallach, M, Smith, NC, Miller, CM, Eckert, J & Rose, M 1994, 'Eimeria-maxima - Elisa And Western-blot Analyses Of Protective Sera', Parasite Immunology, vol. 16, no. 7, pp. 377-383.View/Download from: Publisher's site
Infection of chickens with Eimeria maxima induces the production of parasite-specific antisera which can be used passively to protect naive chickens against infection. Globulin fractions of these antisera can also be used passively to protect chickens. S
Smith, NC, Bucklar, H, Muggli, E, Hoop, R, Gottstein, B & Eckert, J 1993, 'Use Of IGG- And Igm-specific Elisas For The Assessment Of Exposure Status Of Chickens To Eimeria Species', Veterinary Parasitology, vol. 51, no. 1-2, pp. 13-25.View/Download from: Publisher's site
Simple and reliable methods for the determination of the exposure status of chickens to Eimeria species are required. For this purpose an enzyme-linked immunosorbent assay (ELISA) detecting specific IgG and IgM antibodies in serum samples was evaluated.
Smith, NC, Eckert, J & Braun, R 1993, 'Coccidiosis research in Europe', Parasitology Today, vol. 9, no. NA, pp. 236-239.
The cytokine, gamma-interferon (IFN-gamma), which is produced by CD4+ T cells, plays a crucial role in host resistance to Eimeria infections. Karen Ovington and Nick Smith propose that free oxygen radical generation by leukocytes in response to infection
Smith, NC, Ovington, K & Boray, J 1992, 'Fasciola-hepatica - Free-radical Generation By Peritoneal Leukocytes In Challenged Rodents', International Journal For Parasitology, vol. 22, no. 3, pp. 281-286.View/Download from: Publisher's site
Free radical generation by peritoneal leukocytes from hosts able to develop resistance to reinfection with Fasciola hepatica (rats) was compared with that of hosts unable to develop resistance (mice). Free radical generation by rat leukocytes was 3.5 tim
Smith, NC 1991, 'A Role For Protein-kinase-c In The Production Of Free Oxygen Radicals In Response To Nippostronglylus-brasiliensis', Parasitology Research, vol. 77, no. 6, pp. 521-525.View/Download from: Publisher's site
The involvement of protein kinase C in the initiation of free oxygen radical generation by rat leukocytes in response to the nematode Nippostrongylus brasiliensis was investigated. Inhibitors of protein kinase C, trifluoperazine and 1-(5-isoquinolinylsul
Smith, NC, Ovington, K & Bryant, C 1991, 'Free-radical Generation And The Course Of Primary Infection With Nippostrongylus-brasiliensis In Congenitally Athymic (nude) Rats', Parasite Immunology, vol. 13, no. 6, pp. 571-581.View/Download from: Publisher's site
The course of primary infections with Nippostrongylus brasiliensis was followed in nude (CBHR nunu) and heterozygote (CBHR nu+) rats. In both nude and heterozygote rats peak egg production by N. brasiliensis occurred on days 7 and 8 post-infection. How
Ovington, K, Smith, NC & Joysey, H 1990, 'Oxygen Derived Free-radicals And The Course Of Eimeria-vermiformis Infection In Inbred Strains Of Mice', Parasite Immunology, vol. 12, no. 6, pp. 623-631.View/Download from: Publisher's site
Smith, NC 1989, 'The Role Of Free Oxygen Radicals In The Expulsion Of Primary Infections Of Nippostrongylus-brasiliensis', Parasitology Research, vol. 75, no. 6, pp. 423-438.View/Download from: Publisher's site
Smith, NC & Bryant, C 1989, 'Free-radical Generation During Primary Infections With Nippostrongylus-brasiliensis', Parasite Immunology, vol. 11, no. 2, pp. 147-160.View/Download from: Publisher's site
Smith, NC, Bryant, C & Boreham, P 1988, 'Possible Roles For Pyruvate-ferredoxin Oxidoreductase And Thiol-dependent Peroxidase And Reductase Activities In Resistance To Nitroheterocyclic Drugs In Giardia-intestinalis', International Journal For Parasitology, vol. 18, no. 7, pp. 991-997.View/Download from: Publisher's site
Smith, NC & Bryant, C 1986, 'The Role Of Host Generated Free-radicals In Helminth Infections - Nippostrongylus-brasiliensis And Nematospiroides-dubius Compared', International Journal For Parasitology, vol. 16, no. 6, pp. 617-622.View/Download from: Publisher's site
Rajendran, E, Clark, M, Goulart, C, Steinhöfel, B, Tjhin, ET, Smith, NC, Kirk, K & van Dooren, GG, 'Substrate-mediated regulation of the arginine transporter ofToxoplasma gondii'.View/Download from: Publisher's site
ABSTRACTIntracellular parasites, such as the apicomplexanToxoplasma gondii, are adept at scavenging nutrients from their host. However, there is little understanding of how parasites sense and respond to the changing nutrient environments they encounter during an infection.TgApiAT1, a member of the apicomplexan ApiAT family of amino acid transporters, is the major uptake route for the essential amino acid L-arginine (Arg) inT. gondii. Here, we show that the abundance ofTgApiAT1, and hence the rate of uptake of Arg, is regulated by the availability of Arg in the parasite's external environment, increasing in response to decreased [Arg]. Using a luciferase-based 'biosensor' strain ofT. gondii, we demonstrate that parasites vary the expression ofTgApiAT1 in different organs within their host, indicating that parasites are able to modulateTgApiAT1-dependent uptake of Arg as they encounter different nutrient environmentsin vivo. Finally, we show that Arg-dependent regulation ofTgApiAT1 expression is post-transcriptional, mediated by an upstream open reading frame (uORF) in theTgApiAT1 transcript, and we provide evidence that the peptide encoded by this uORF is critical for mediating regulation. Together, our data reveal the mechanism by which an apicomplexan parasite responds to changes in the availability of a key nutrient.
Smith, NC, Fell, A & Good, MF 1998, 'The immune response to asexual blood stages of malaria parasites', KARGER, pp. 144-162.
Smith, NC, Miller, C, Petracca, M & Eckert, J 1995, 'Techniques for detecting immune responses of avian hosts' in Biotechnology : Guidelines on Techniques in Coccidiosis Research, European Communities Publications, Luxembourg, pp. 164-175.
Smith, NC, Roditi, I & Shirley, MW 1995, 'Biochemical and molecular techniques for identification of Eimeria species and strains' in Eckert, J, Braun, R, Shirley, MW & Coudert, P (eds), Biotechnology : Guidelines on Techniques in Coccidiosis Research, European Communities Publications, Luxembourg, pp. 120-138.
Boreham, P, Smith, NC & Shepherd, R 1989, 'Drug resistance and the treatment of giardiasis' in Advances in Giardia Research, University of Calgary Press, Calgary, pp. 1-9.
Belli, SI, Ferguson, DJ, Luxford, C, Davies, MJ, Wallach, M, Finger, A & Smith, NC 2004, 'The molecular basis of the poultry coccidiosis vaccine, Coxabic', Proceedings of the 53rd Western Poultry Disease Conference, Proceedings of the 53rd Western Poultry Disease Conference, pp. 68-70.
Belli, S, Witcombe, D, Teasdale, C, Gleeson, M, Wallach, M & Smith, NC 2002, 'Development of a recombinant subunit vaccine against coccidiosis in poultry incorporating asexual and sexual stage antigens from Eimeria maxima', Proceedings of World Poultry Science Association Asian Pacific Federation Conference, Proceedings of World Poultry Science Association Asian Pacific Federation Conference, pp. 561-564.
Smith, NC 1998, 'Progress towards a vaccine against poultry coccidiosis: the potential harnessing of maternal immunity', ICOPA IX - 9th International Congress of Parasitology, International Congress of Parasitology, Monduzzi Editore, Bologna, pp. 233-238.