Research projects are available with the faculty in the following areas: Mackinnon Group, Functional Anatomy, Veterinary Virology, Microbiology and Immunity, Parasite Genomics and Genetics, Veterinary Pharmacology, Parasitology and Veterinary Pathology.
Weaner Scours Syndrome in Merino Sheep
The Mackinnon project team are currently investigating aspects of the biology, transmission and control of a weaner scours syndrome affecting merino sheep in South Eastern Australia. The work is funded through Meat and Livestock Australia and involves developing a better understanding of the aetiology, transmission and epidemiology of this syndrome. The syndrome is responsible for mortalities, weight loss and scouring in sheep from weaning to 16 months of age and causes considerable economic and welfare issues for producers annually. Two honours projects are available as described below. Both projects involve both field (on‐farm) and lab based work and students will work as part of the Mackinnon project team to develop a deep understanding of their area of work plus a broader appreciation of the industry importance of the project. There is little information currently available regarding aetiology and epidemiology of this syndrome in Australia except through the opportunistic collection of outbreak samples and data submitted to the regional veterinary diagnostic laboratories. Hence involvement in this project offers students an opportunity to contribute to a developing knowledge base. The importance of this syndrome is compounded by the fact that Yersinia species are zoonotic organisms with both human health and food safety implications.
The relationship between the molecular epidemiology of field isolates of Yersinia species and severity of disease in weaner sheep.
A library of over 600 Yersinia isolates has been collected over the past 20 months. These isolates have been processed in PCR and confirmed as Yersinia species. Further differentiation between Yersinia isolates will be generated through biotyping and serotyping isolates in the laboratory. There is known high correlation between biotype and serotype and pathogenicity of the organism. This is important for relating subtype to the severity of disease, particularly as Mackinnon researchers have recorded significant disease due to Yersinia species previously believed to be only rarely involved in this syndrome. This information will also contribute towards vaccine development for field trials in 2014. The student undertaking this project will learn laboratory techniques including traditional microbiological and molecular techniques for differentiation of Yersinia species. They will also be involved in the vaccine trials to be conducted as part of the project in 2014.
Investigating the environmental survival of pathogenic Yersinia species for understanding patterns of transmission and disease in livestock species.
Acute “outbreaks” of disease in livestock are associated with the shedding in faeces of large numbers of this organism and therefore significant environmental contamination. However, the ability to survive or even replicate in the environment has not been investigated, particularly under a wide range of climatic conditions. This project will be complimentary to project 1 described above and will also run concurrently with the vaccine work being undertaken by Mackinnon project in 2014. This will facilitate investigation of under which environmental conditions Yersinia species survive most readily and implications of these findings for transmission and disease establishment in livestock species. The work will involve both on‐farm investigations and a controlled experiment conducted at the Werribee campus. The student involved in this project will also work as an integral part of the Mackinnon project team. The outcomes of this work will assist in the development of management recommendations for sheep producers who experience significant issues with the weaner scours syndrome, facilitate a better understanding of the potential for cross species transmission of this organism and will contribute to a better understanding of the implications for human disease risk from this organism, in particular via poorly stored or processed food of animal origin.
Supervisor: Dr. Helen Davies
Location: Parkville & Werribee
Co‐Supervisor(s): Dr Jonathan Merritt
Research in the functional anatomy and biomechanics group involves two areas. The first area is the morphology and biomechanics of the distal equine forelimb. This includes the development of methods of predicting and preventing breakdown in exercising horses because this is the region where the vast majority of breakdowns occur. The second area of research is directed towards an understanding of anatomical connectivity and the control of locomotory movements. This includes work towards a more complete elucidation of the role of connective tissue structures in distributing load throughout the body in quadrupeds (horses, greyhounds and cats) and the role of specific muscles in the control of movements. Projects within both these areas are available and can be tailored to suit individuals to provide experience in various skills including research methods, animal handling, observational and deductive skills, anatomy, diagnostic imaging, and/or computer modelling.
a. Functional anatomy of the locomotor system of horses
- Fascial connections of the nuchal ligament.
- Fascial connections within the forelimb.
- Fascial connections between the forelimb and trunk.
- Fascial connections in the thoracolumbar spine.
- Digitising skeletal elements.
All these projects are part of the basic research required to develop functional models of the equine locomotor apparatus which may then be used to identify relationships between conformation, training, performance and breakdown. The first four involve extensive dissection of cadavers and the observation of live horses. The fifth involves learning to prepare skeletons, digitise objects, and to manipulate modelling programs.
b. Neurological control of locomotion
- Innervation of specific muscles in the dog and/or cat.
This project involves dissection of dogs and/or cats, preparation of histological specimens and the measurement of histological features in those specimens.
Herpesviruses in Australian wildlife
Supervisor: Dr Joanne Devlin
Telephone: 9035 8110 | Facsimile: 8344 7374
Co-Supervisor(s): Dr Carol Hartley, Dr Jane Owens
Herpesviruses are known to cause disease in Australian wildlife, especially in animal populations that are under stress from other factors such as habitat destruction, concurrent disease and human encroachment. This project will characterise newly discovered herpesviruses in Tasmanian Devils and other Australian marsupials and will include a combination of classical laboratory virology techniques (including cell culture, virus isolation, virus-serum neutralisation assays), molecular biology technology (PCR assays, sanger DNA sequencing) and potentially next-generation sequencing techniques and bioinformatics analyses. This project will help us to understand the significance of these viruses for wildlife health.
Feline Calicivirus in Australian Cats
Supervisor: A/Prof James Gilkerson and Prof Glenn Browning
Co‐Supervisor(s): Dr Sally Symes
This project is interested in investigating feline calicivirus as a cause of upper respiratory tract disease in cats. Molecular techniques, such as quantitative RT‐PCR, will be used to ascertain the significance of this virus in Australian cat populations.
Understanding the role of glycoprotein G in canine herpesvirus‐1 infection and immunogenicity.
Supervisor: Dr Carol Hartley
Co‐Supervisor(s): A/Prof James Gilkerson
While virus proteins directly involved in the machinery of herpesvirus replication are well described, there is less known about the contribution of other proteins to the way herpesviruses cause disease. Glycoprotein G is present in diverse alphaherpesviruses and in several viruses can modulate the innate inflammatory response to infection and alter virus pathogenicity. Canine herpesvirus 1 (CHV1) is an alphaherpesvirus that causes fatal haemorrhagic disease in neonates and mild upper airway and genital tract infections in adult dogs. The first aim of this study is to express and purify recombinant CHV1 glycoprotein G in order to develop an ELISA to define the seroprevalence of antibodies to this virus in Australia. The second aim of this study is to characterise the expression on this protein during CHV1 infection in vitro, and to determine whether CHV1 gG can, like other herpesvirus gG’s, can act as a viral chemokine binding protein.
Technical guide: The candidate will develop skills in molecular biology (PCR and cloning); protein expression, purification and analysis; ELISA; virology and cell culture.
Gammaherpesvirus infection of horses; defining viral loads and sites of infection after reactivation from latency
Supervisor: Dr Carol Hartley
Co‐Supervisor(s): A/Prof James Gilkerson
Gammaherpesviruses are slow growing, highly cell associated viruses with well-known members including Epstein Barr virus and Kaposi's sarcoma herpesvirus. Two closely related and widespread gammaherpesviruses are known to infect horses and both are isolated in clinically well horses, and in horses with disease. The ability to determine the presence or absence of these viruses in infected horses has not been sufficient to identify a role for these viruses in clinical disease. This project will develop a quantitative PCR measure viral load and a quantatitive RT‐PCR to measure viral replication. These assays will be applied to a set of samples (nasal, eye and oral swabs and peripheral blood) from horses that have been immunosuppressed with high dose corticosteroids, to characterise the dynamics of the viral load in different sites after reactivation from latency. These assays can then be applied better define pathogenesis of infection, sites of latency and associations of viral load with signs of clinical disease.
Technical guide: The candidate will develop skills in molecular biology (quantitative PCR and cloning); virology and cell culture.
Microbiology and Immunity
Examining how Protease Activated Receptor 1 regulates innate immune signalling and bacterial‐driven inflammation
Supervisor: Associate Professor Phil Sutton
Location: Murdoch Childrens research Institute
Co‐Supervisor(s): Dr Garrett Ng
The main interests of the Mucosal Immunology group are: 1) the investigation of mechanisms that regulate bacterial pathogenesis, in particular host factors that regulate the inflammatory response to infection by bacterial pathogens; 2) the development of vaccines against mucosal pathogens.
Project Description: Protease Activated Receptors (PAR) are a family of sensors that detect the presence of proteases released during infection and inflammation. Increasing evidence suggests they play an important part in the regulation of the inflammatory and immune response to infection, but the mechanism by which this occurs is poorly understood.
We have found that one member of this family, PAR1, is an important regulator of the inflammatory response to infection with the human pathogen Helicobacter pylori, the main causative agent of stomach cancer (Ref 1). Recently we have shown that this mechanism involves regulation of cytokine production by the suppression of the transcription factor IRF5, thereby inhibiting both Th1 and Th17 responses to this infection (Ref 2). However PAR1 has important other activities that are not understood. In particular, our unpublished data show that PAR1 differentially regulates the immune response to Toll‐Like Receptor (TLR) signalling. PAR1 deficiency increased the IL‐6 response of splenocytes stimulated with TLR2 ligand but decreased KC in the same cultures (Figure). The opposite was seen with TLR7, while no response to TLR4 or TLR9 activation was seen in PAR1‐/‐ cells (Figure). Thus the activation of PAR1 likely plays an important but complex and varied role in modifying the innate immune response to pathogenic infection. Why the effect of PAR1 varies for different TLR is unknown, as is which individual immune cell type populations PAR1 is affecting, and how this affects the response to pathogenic stimulation.
The aims of this project will be:
- To examine the role of PAR1 on the response of individual immune cells to TLR activation.
- To examine the mechanism by which PAR1 regulates TLR signalling in these cells.
- To examine the effect of PAR1 regulation on the TLR response to pathogenic stimulation.
Techniques commonly used in this laboratory:
Bacterial cultivation, bacterial infection of mice, colony forming assay, analysis of inflammation in mouse infection models, analyses of in vivo immune response to infection, cell culture, FACS, cell sorting, molecular biology, RT-PCR, real-time PCR, western blotting, ELISA.
- Wee J, Chionh Y-T, Ng G, Harbour S, Allison C, Pagel C, Mackie E, Mitchell H, Ferrero R & Sutton P (2010) Protease Activated Receptor-1 down-regulates the murine inflammatory and humoral response to Helicobacter pylori. Gastroenterology 138: 573–
- Chionh Y, Ng G, Ong L, Arulmuruganar A, Stent A, M Saeed, Wee J & Sutton P. (2014) Protease Activated Receptor 1 suppresses Helicobacter pylori gastritis in mice via the inhibition of macrophage cytokine secretion and Interferon Regulatory Factor 5. Mucosal Immunology doi: 10.1038/mi.2014.43.
This project may involve handling of infectious organisms and animal experimentation. All procedures will be carried out in a PC2 level laboratory following appropriate standard operating procedures. Appropriate training in PC2 level procedures, bacteriological techniques and animal handling will be provided.
How resilient is T cell immune memory?
Supervisor: Dr Alison Every
Co‐Supervisor(s): A/Prof Jean‐Pierre Scheerlinck
Long‐lived immune memory develops after vaccination or infection allowing robust immune responses capable of rapidly clearing the pathogen following re‐infection. However, in some instances, this immune memory response is ineffective and unable to clear the pathogen. In this project, the Honours student will define factors and/or conditions that determine the degree of resilience of the immune memory response to manipulation by the pathogen. This project will involve vaccination of mice with a model antigen plus one of several different adjuvants. The types of immune memory induced will be characterised using tissue culture, flow cytometry, cytokine and antibody ELISAs and intracellular cytokine staining.
Parasite Genomics and Genetics
Defining new molecular markers for the diagnosis and characterisation of Theileria orientalis complex from cattle from Victoria
Supervisor: Dr Abdul Jabbar
Telephone: 03 9731 2022
Facsimile: 03 9731 2366
Co-Supervisor(s): Professor Robin B. Gasser
Since 2006, Australia has seen more than 500 clinical outbreaks of oriental theileriosis (caused by Theileria orientalis) in cattle industry, mainly in the states of New South Wales and Victoria. Diagnosis of the infection is predominantly made by microscopic, serological and molecular tools. However, molecular tools are paramount for the genetic characterization of the ‘pathogenic’ genotypes of the parasite. For the last 20 years, essentially two molecular markers (i.e., part(s) of major piroplasm surface protein (MPSP) and/or small subunit of nuclear ribosomal RNA (SSU) genes) have been used to characterise various genotypes of the parasites. Genotypes defined using these two genes have not been independently verified by other molecular markers. This project will focus on defining new markers (nuclear as well as mitochondrial) for the diagnosis and characterisation of T. orientalis complex from cattle from Victoria.
Technical guide: The candidate will develop skills in molecular biology, bioinformatics and phylogenetic analyses.
Characterisation of sheep tapeworms (Moniezia spp.) from Australia using morphological and molecular‐phylogenetic approaches
Supervisor: Dr Abdul Jabbar
Telephone: 03 9731 2022
Facsimile: 03 9731 2366
Co-Supervisor(s): Professors Ian Beveridge and Robin B. Gasser
Members of the genus Moniezia are anoplocephalid cestodes of ruminants. Important species of the genus are Moniezia expansa which is the main small intestinal tapeworm of sheep, and Moniezia benedeni that predominantly infects cattle. Recent studies aimed at the molecular characterisation of some related cestodes of Moniezia from macropod marsupials have revealed that there are substantial genetic differences within single morphotype(s), suggesting the presence of several species within the complex. Based on our experience in molecular epidemiology of parasites, we hypothesise that there would be genetic variation within the single species of the genus Moniezia. The present project will aim to determine genetic variation within and between Moniezia spp. from sheep from various parts of Australia using molecular-phylogenetic approaches.
Technical guide: The candidate will develop skills in morphological identification of cestode parasites aswell as in molecular biology, bioinformatics and phylogenetic analyses.
Use patterns for prescription pharmaceuticals in small animal veterinary practice
Supervisor: Prof Ted Whittem
Location: Werribee or Parkville
Companion animal veterinarians prescribe and dispense restricted prescription animal remedies and human prescription drugs for use in animals. Over the last 20 years the number of available drugs in each therapeutic class has multiplied greatly. This project will evaluate the absolute and relative quantities of different drugs used in Victorian companion animal practices, probing for use patterns that reflect covariables such as age, experience, nationality, geographical location of the practitioner and practice. This project will suit students who have an interest in statistics, pharmacology and skills in verbal communication and may be targeting a career in pharmaceutical technical services, marketing or sales.
Technical Guide: The candidate will acquire or polish skills in project planning and design, design and conduct of surveys, evaluation of wholesale and retail sales data, database management and data analysis.
Haemoglobin digestion as target for vaccine development in schistosomes; Insertional mutations to identify intervention targets
Supervisor: A/Prof Bernd Kalinna
Co‐Supervisor(s): Prof Robin Gasser (tentative)
Schistosomiasis is amongst one of the most severe parasitic diseases of the developing world, threatening millions of people with chronic illness, disfigurement, or death, that can result from the parasitic infection. The disease is endemic in 76 countries and over 250 million people are infected worldwide, which is testimony to its public health significance. Chemotherapy with praziquantel is faced with the problem of drug resistance and vaccines are not available. Disease reoccurrence in several regions reinforces the need for active surveillance and novel approaches for treatment and prevention. Therefore, identification of new drug targets, development of effective vaccines and diagnostics methods constitutes a major public health priority.
For functional analyses gene trapping is a high‐throughput approach that is used to introduce insertional mutations across the genome. When inserted into an expressed gene, the gene trap cassette is transcribed from the endogenous promoter of that gene in the form of a fusion transcript. The gene trap simultaneously inactivates and reports the expression of the trapped gene at the insertion site, and provides a DNA tag for the rapid identification of the disrupted gene.
The key hypothesis to be tested in this project is that the transduction of developmental stages of S. mansoni with Moloney Murine Leukaemia Retrovirus can be employed as a gene trap system for the analysis of gene function in schistosomes.
Techniques commonly used in this laboratory: Cell culture, Molecular Biology Techniques (PCR, gene cloning, site directed mutagenesis, Southern Blots, Northern Blots, real time PCR, recombinant protein production etc).
Investigation of intervertebral disc degeneration in older dogs.
Supervisor: Dr Barbara Bacci
Co‐Supervisor(s): Prof. Ron Slocombe
Intervertebral disk degeneration is a common condition in mature and geriatric dogs. Degenerative compositional changes in the nucleus pulposus and annulus fibrosus predispose individuals to clinical intervertebral disk disease (IVDD). There are breed differences in both the rate and the nature of disc degeneration. In chondrodystrophic breeds changes occur early and involve the nucleus pulposus, which is replaced by cartilage, while in non‐chondrodystrophic breeds degenerative changes occur later in life and mostly involve the annulus fibrosus. The cause of the degeneration and the degenerative process are not fully understood. The project is aimed at identifying intervertebral disk changes by histological examination of disks from thoracic and lumbar tracts in dogs of different age, breed and health status. Post‐mortem samples will be collected shortly after death, processed for routine histological examination and histochemical stains will be performed to better understand the connective tissue reactions as discs degenerate. The candidate will acquire skills in post‐mortem sample collection, tissue processing and in the interpretation of histological specimens using routine and special stains.
- Hunter et al. “Three dimensional architecture of the notochordal nucleus pulposus: novelobservations on cell structures in the canine intervertebral discs”. J Anat (2003), 202, pp279‐291
- Zhang et al. “ Histological features of the degenerating intervertebral disc in a goat disc‐injury model” Spine (2011) 36,pp1519‐1527