Research Interests

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.

Projects

The molecular basis for oocyst and cyst wall formation in apicomplexan parasites

Apicomplexan parasites such as Eimeria, Neospora, Toxoplasma and Plasmodium are single celled organisms - protozoa - that cause some of the most serious infectious diseases of livestock and humans ever known. Transmission of these parasites is dependent on their ability to encase themselves in protective structures known as oocyst or cyst walls. These walls are resistant to harsh environmental conditions, chemicals and attack by the immune system. We will discover and characterise the molecular basis for cyst wall formation. This fundamental knowledge will be the building block for new, highly specific drugs and vaccines to control these extremely important pathogens.

The virulence of intracellular parasites: the role of activation and suppression of P2X7 receptors

Toxoplasmosis and leishmaniasis pose a threat to the health and well-being of the Australian human and animal populations. Around 6-8 million Australians are infected with Toxoplasma, a parasite that can cause severe problems in immunosuppressed individuals and birth defects and miscarriage in pregnant women with a primary infection. Toxoplasmosis is also the main cause of abortion and stillbirth in Australian sheep. Leishmaniasis, recently found in Australia, is a risk for overseas travellers, livestock and wildlife. Our research aims to provide an understanding of what makes these parasites successful. Both Toxoplasma gondii and Leishmania major, can suppress the host's immune response in the parasites' favour, enabling them to replicate unabated during the initial phase of infection. Exactly how they do this has never been fully elucidated. We are the first to investigate the role of P2X7 receptors (which are implicated in the pathogenesis of a variety of diseases) in enabling the host to prevent infection by Toxoplasma and Leishmania. We will also determine the countermeasures used by these parasites that allow them to establish a chronic infection. This will advance the understanding of host-parasite relationships and enable us to develop rational control strategies to combat these chronic diseases.

Efficacy trials of a maternally-delivered recombinant vaccine against coccidiosis

Coccidiosis caused by species of Eimeria costs the poultry industry an estimated $1 billion per year worldwide.  The resistance of the parasite to currently used drugs, the high cost of research and development of new anticoccidial agents ($100 million for each new drug) and the demands by the public for chemical-free agricultural practices drive the quest for a vaccine to control this disease.  Field trials of native gametocyte antigens isolated from Eimeria maxima have been, or are being, conducted in Israel, Sweden, South Africa, Thailand, the USA and Argentina and have confirmed the utility of the vaccine.  This vaccination strategy based on maternal immunity has several advantages over more orthodox vaccines : (1) it is economical because only the mothers are vaccinated and, since a breeding hen will produce 100-150 young, the costs of vaccination are reduced at least 100 fold; (2) chickens can be protected from the moment they hatch; (3) since maternal antibodies are a natural element in developing chickens and are naturally cleared from the birds as they grow, there is no residue in the meat; (4) there is no toxicity to the chicks or other domestic animals and there are no hazards for broiler house personnel; (5) the vaccine is a "dead" vaccine, precluding the problem of reversion to virulence and escape of live parasite vaccine isolates; and (6) stressful handling of chicks in order to administer the vaccine is not required.  We have now cloned and expressed recombinant versions of the gametocyte antigens to succeed the native antigens as a second generation anticoccidial vaccine. The efficacy of the recombinant proteins will be tested in this project.  A recombinant version of the vaccine will allow simplification of production and quality control because it will avoid cycling of parasites through chickens.  The recombinant vaccine may therefore also be cheaper since the high costs of maintaining chickens pathogen free to ensure the safety and quality of the native vaccine can be avoided.

Research Team

Assoc. Prof. Nick Smith (Chief investigator)
Prof. Michael Wallach (Chief Investigator)
Dr Marilyn Katrib ( Research Fellow/ Lecturer)
Dr Catherine Miller (Research Fellow)
Iveta Slapetova (Research Assistant)

Michelle Robinson (Research Assistant)
Kelly Mai (PhD student)
Sarah Flowers (PhD student)
Robert Walker (PhD student)
Michael Lees (PhD student)

Alana Zakrzewski (PhD student)

Rowan Ikin (PhD student)

Phillipa Sharman (Honours Student)

Collaborators

Dr Avner Finger (Abic Ltd)
Prof. David Ferguson (Oxford University, UK)
Prof. Brian Chait (Rockefeller University, USA)
Prof James Wiley & Dr Steve Fuller (Nepean Hospital, University of Sydney)

Selected Publications

 1. Belli SI, Smith NC, Ferguson DJ. The coccidian oocyst: a tough nut to crack! (2006) Trends Parasitol. 22:416-23

2. Smith NC, Tilley L, Thompson RC, Ryan UM, Loukas A, Jenkins D, McFadden GI. (2006) An Australian network to support the understanding and control of parasites. Trends Parasitol. 22:97-9.

3. Belli SI, Mai K, Skene CD, Gleeson MT, Witcombe DM, Katrib M, Finger A, Wallach MG, Smith NC. (2004) Characterisation of the antigenic and immunogenic properties of bacterially expressed, sexual stage antigens of the coccidian parasite, Eimeria maxima. Vaccine. 22:4316-25.

4. Witcombe DM, Ferguson DJ, Belli SI, Wallach MG, Smith NC. (2004) Eimeria maxima TRAP family protein EmTFP250: subcellular localisation and induction of immune responses by immunisation with a recombinant C-terminal derivative. Int J Parasitol. 34:861-72.

5. Ferguson, D.J.P., Belli, S.I., Smith, N.C. and Wallach, M.G. (2003) The development of the macrogamete and oocyst wall in Eimeria maxima: Immuno-light and electron microscopy.  International Journal for Parasitology 33:1329-40

Industry Affiliations

ABIC Veterinary Products Ltd