Honours Projects in the School of Veterinary and Biomedical Sciences

2009/2010

Global gene expression profiling of canine lymphoma

Lymphoma, a cancer of lymphoid tissue, is a relatively common form of malignancy in the dog yet very little is understood about its pathogenesis. As with other forms of cancer, canine lymphoma is likely to be a molecular disease resulting from the abnormal expression of genes involved in fundamental cell processes such as cell differentiation, proliferation and apoptosis.  In this project, methods for isolating RNA of suitable quality from archived tissue will be examined, for the purpose of running Affymetrix GeneChips that can analyse thousands of dog genes in parallel. This should greatly enhance our understanding of lymphoma pathogenesis in the dog and will have utility in improving the diagnosis, prognosis and treatment of this lethal disease.

For more information contact:

Dr Wayne Greene
VBS room 3.041
Tel: 9360 2545
Email: W.Greene@murdoch.edu.au

TOP

Molecular Detection of Cryptosporidium in Fish

Water is increasingly recognised as an important vehicle for transmission of Cryptosporidium. The oocyst is environmentally stable and resistant to inactivation by chlorine at doses commonly used in drinking water treatment. Cryptosporidium can survive for long periods in both freshwater and saltwater and viable human-infectious oocysts have been recovered from several bivalve species.

Little is known about the prevalence, geographical distribution of species of Cryptosporidium infecting fish and what the potential health implications are.

The objective of this study is to analyse fish from selected locations in order to determine (a) the prevalence of Cryptosporidium in these fish using microscopy and PCR and (b) to determine whether human-infectious genotypes of Cryptosporidium are found in fish using PCR and sequencing techniques. This study will therefore provide important information on not only the biology of Cryptosporidium infecting fish as well as the transmission dynamics of Cryptosporidium and will also identify if there are any public health implications.

Do sheep and cattle contaminate water catchments with human infectious Cryptosporidium and Giardia?

Cryptosporidium and Giardia are important enteric parasites that infect a wide range of mammals including humans. Cattle have long been implicated as being an important reservoir of human infectious species of Cryptosporidium and Giardia. Recent evidence in the US however suggests that Cattle are infected with numerous species of Cryptosporidium and Giardia, most of which are not infectious to humans. Little is known about the species of Cryptosporidium and Giardia in cattle and sheep in Australia. This project will involve using PCR screening and DNA sequencing to determine the prevalence and species of Cryptosporidium and Giardia infecting pre and post-weaned cattle and sheep in Western Australia. The data generated from this study will provide important information towards understanding the transmission dynamics of Cryptosporidium and Giardia.

Proteomics analysis of Cryptosporidium life cycle stages using Maldi Imaging

Cryptosporidium has a world-wide geographic distribution, can remain viable under cool, moist conditions for many months, and is resistant to conventional disinfectants used by the water industry to disinfect water, including chlorine. It has been responsible for numerous water-borne outbreaks of disease and represents the major public health concern of water utilities in developed nations.

Recent developments in in vitro cultivation have revealed that Cryptosporidium can complete its life cycle in media devoid of host cells, contradicting the current viewpoint that it can only grow on host cells. As the oocyst is believed to be the only stage in the life cycle capable of surviving in the environment, current detection methods for Cryptosporidium within the water industry and studies conducted to assess the survival of Cryptosporidium under environmental conditions have focused on the oocyst. Preliminary work in our laboratory demonstrated the presence of Cryptosporidium life cycle stages appearing in samples, which had been stored in water for long periods of time.  Nothing is known about what proteins are expressed in different life-cycle stages and which proteins could be used as biomarkers to identify, concentrate and analyse different life-cycle stages. The aim of this study is to apply Maldi-imaging mass spectrometry to identify and characterse proteins, which are expressed in life cycle stages.  The data generated from this project will be used to generate biomarkers for life-cycle stages.

Examination of the efficiency of Phylomer peptides and Chinese herbs in the control of human and animal infectious diseases.

Cryptosporidium is an enteric parasite, which has a global impact on the health, survival and economic development of >10 million people and animals worldwide, for which no effective chemotherapy is available. Clinical manifestations of cryptosporidiosis vary with age and immunological status. Immunocompetent individuals may have voluminous but self-limiting diarrhea, however, in immunodeficient individuals; cryptosporidiosis can be associated with chronic, diarrhoea with a fatality rate as high a 60%.
We have identified a series of phylomers (naturally constrained peptide subdomains) in collaboration with a Perth-based biotechnology company called Phylogica), which inhibit the growth of Cryptosporidium by targeting purine salvage enzymes in the parasite. It has been shown that Phylomers can be successfully delivered across the cell membrane using protein transduction domains. Preliminary evidence suggests that phylomers have broad-spectrum anti-microbial activity.
This project is a collaboration with Professor Songhua Hu at Zhejiang University in China. Professor Songhua Hu has successfully used Chinese herbs in treating animal diseases such as bovine mastitis. The study will involve testing Chinese herbs and Phylomers on Cryptosporidium and a range of other pathogens. Techniques learned will include cell culture, drug testing, qPCR and spectrophotometry.

Prevalence and genetic characterisation of blood-borne parasites in Urban adapted Possums

The Common brush-tailed possums (Trichosurus vuplecula) is one of the most abundant and widespread native marsupials in urban Australia. Possums have flourished in urban areas by adapting their diet to include food scraps and garden plants found in abundance in residential areas, public parks, botanic gardens and zoos.  These aspects of possum ecology have promoted interaction with humans, domestic pets and other introduced animals facilitating the transmission of pathogens, some of which are infectious to humans. Blood-borne parasites have been identified at a high prevalence in other marsupials but nothing is known of their prevalence in possums.  This study will determine the prevalence and identity of blood-borne parasites in Common brush-tailed possums that live at high density at the urban interface. DNA will be extracted from blood and parasites such as theileria and trypanosomes will be screened for by PCR and their DNA will be sequenced to identify them. The data generated will be used to understand if these parasites are impacting on host health and if possums harbour human-infectious species of blood parasites.

Biological characterisation of a new species of Cryptosporidium in pigs

Ever want to be involved in the naming of a new species? A new species of Cryptosporidium has recently been detected in pigs, which is genetically very distinct. In order for this species to be formally described in the literature, more information on its biological characteristics is required. This project aims to characterise both the biological characteristics of this species and to further characterise its molecular characteristics. It is anticipated that the results of this project will contribute greatly to our understanding of cryptosporidiosis in pigs and will also result of the formal naming of this species in the scientific literature.

TOP

Can Australian marsupials transmit Giardia to humans? 

Giardia is a protozoan parasite and one of the most common causes of diarrhoea in humans and animals. In Australia, marsupials are one of the dominant mammalian groups within watersheds. It is therefore important to investigate the occurrence of Giardia in marsupials to determine whether infections pose a potential threat to public health, so that appropriate catchment management strategies may be implemented. Little is known of the prevalence and genotypes of Giardia infecting marsupials, although preliminary research suggests that they can be infected with human-infectious species.

The objective of this study is to screen marsupial fecal samples using molecular tools from areas of high and low human interaction in order to determine (a) the prevalence of Giardia in marsupials by PCR and (b) to determine whether human-infectious genotypes of Giardia are found in marsupials using PCR and sequencing techniques. This study will therefore provide important information on not only the biology of Giardia infecting marsupials as well as the transmission dynamics of Giardia and will also identify if there are any public health implications.

For more information on the above projects contact:

A/Prof. Una Ryan
Room 3.45
Tel: 9360 2482
Email: Una.Ryan@murdoch.edu.au

Canine vector borne diseases in Korea

Funding: Already granted by the Australia-Korea Foundation.

This will involve laboratory-based molecular biology techniques looking at the blood and ticks from dogs in Korea and possibly Taiwan to identify vector-borne diseases such as Babesia and also Ehrlichia and Anaplasma and determining the clinical effects these organisms have on dogs.

For more information contact:

Haemoprotozoan Parasites of Birds

Supervisors: Associate Professors Peter Irwin and Una Ryan

Would you like to be involved in naming a new species of haemoparasite… or maybe two species?  If so we have just the project for you!  This study aims to identify the species of piroplasm parasite (Babesia, Theileria or possibly Plasmodium [“malaria”] spp.) in the blood of gannets and gulls sampled during a larger study around the New Zealand coastline.  We have DNA samples and ticks from these birds.  The project will involve the design of suitable primers to detect the haemoparasite DNA using the 18S, HSP or other genes, sequencing, limited cloning experiments and phylogenetic analysis.  This is an exciting area of molecular phylogenetic study; relatively little is known about the haemoparasite species that affect birds and there have been only a handful of molecular-based studies to date.  The project is ready to go … just waiting for someone to sign on to hone their molecular biology skills!

For more information please contact:

Dr Peter Irwin
Tel: 9360 2590
Email: P.Irwin@murdoch.edu.au

Muscle biochemistry in prime lambs and pigs

This project will investigate the biochemical and production factors influencing muscle biochemistry and in particular heme iron levels in prime lambs and/or pork.

For more information contact:

Regulation of omega 3 in lamb meat

There are a number of projects possible to define the genetic and nutritional regulation of omega 3 fatty acids in lamb meat.

The effects of very fast chilling on lamb tenderness

This project will investigate an understanding of the impacts of very fast chilling on lamb meat quality.

Understanding factors that effect beef quality in Western Australia

This project would investigate the Meat Standards Australia database of graded beef carcasses to underpin the factors effecting beef quality in Western Australia.

Muscle biochemistry in prime lambs - effects of genetic selection

Selection for muscling has been shown in other species to impact on the expression of muscle fibre type, enhancing the proportions of Type IIB fibres. This has broad implications for industry, including altered pH characteristics post mortem, altered carbohydrate metabolism, and altered colour. This project assesses these various biological impacts in prime lambs.

Lean meat yield in Merino lambs

Selection for muscling has been shown in other species to reduce the proportion of fat in the carcase. It may also alter the distribution of muscle tissue across the carcase. This is potentially important as increased lean meat yield, and greater proportion of muscling at economically valuable sites will increase return. It is also important to assess the ability of abattoir systems such as VIAscan (Video Image Analysis) to predict carcase lean meat yield in extreme muscling genotypes. This project tackles these issues in the Merino prime lamb industry.

For more information on these projects contact:

Understanding retail colour display in lamb meat

Gene markers for tenderness in Bos indicus and Bos tauris cattle

For more information contact:

TOP

Regulation of pH decline in post mortem muscle

The rate of pH decline post-mortem is an extremely important factor determining meat quality. A range of biological factors may affect this rate, including management practices of the animals prior to slaughter, and aspects of muscle biochemistry. Electrical stimulation has a powerful effect on rate of pH decline, and may interact with these biological aspects. This project aims to explore these interactions.

For more information contact:

Effect of oestrogen in wound healing: Molecular studies in an ovariectomized sheep model

Chronic wounds in humans increase in prevalence with age.  Most chronic wounds affecting the elderly are leg ulcers, with venous ulcers accounting for around 70% of all cases. Research also shows that sex steroid hormones have a powerful effect on wound healing processes. 

In mice, ovariectomy delays reepithelialisation, increases the local inflammatory response and decreases collagen deposition. Recent studies by our colleagues show that oestrogen also increases the expression and nuclear translocation of Flightless I (FliI), an actin-remodelling protein and co-activator of the oestrogen nuclear receptor, which appears to be required for oestrogen-mediated collagen I secretion.  FliI may affect the transcription of genes involved in the wound healing process regulated by the oestrogen receptor  including epidermal growth factor (EGF) receptor, tumour necrosis factor-a (TNF-a) and c-fos, a component of activator protein-1 (AP-1) which regulates TGF-b gene expression.

Declining levels of oestrogen and/or DHEA in humans may contribute to age-related impaired wound healing. This concept is supported by the findings that the use of hormone replacement therapy (HRT) by elderly women appears to reduce the risk of venous ulceration and that a genetic association exists between single nucleotide polymorphisms in the oestrogen receptor gene and risk of venous ulceration. In aged humans of both sexes, the topical application of oestrogen reduces the inflammatory response and significantly reduces wound size.

Here at Murdoch we have used the ovariectomised sheep model to show significant new evidence of a decline in the quality and quantity of collagen in connective tissues from a range of sites after ‘surgical menopause’.  This large animal model now provides an excellent opportunity to study the mechanisms of age and gender effects on wound healing. 

Project Outline    This Honours project will specifically address whether ovariectomy of adult sheep is associated with:

1. Impaired healing of acute wounds via increased inflammation, delayed epithelialisation and reduced collagen deposition
   
   
2. Changes in the expression of genes involved in wound healing that are regulated by the oestrogen receptor (FliI, TNF-a, EGF and TGF-b).

 Main Techniques     Opportunity to participate in sample collection from sheep, histology, digital image processing, immunohistochemistry, quantitative RT-PCR.

Collaborators: UWA and University of Adelaide medical faculties

There is excellent potential for this research to extend into Masters or PhD studies.

For more information contact:

Dr Martin Cake
Room 1.007
Tel: (08) 9360 2175
Email: mcake@murdoch.edu.au

The Characterisation of a Novel Flagellate from Laboratory Mice

The project will involve the identification and characterisation of a novel flagellate found to be common in the caecum of laboratory mice, and determination of whether it is a parasite or commensal. This will involve in vitro culture to amplify flagellates from mice; application of appropriate molecular tools in order to compare the flagellate with related intestinal flagellates from mice and other mammals; and a detailed morphological description using scanning electron microscopy at the Centre for Microscopy, Characterisation and Analysis, UWA.

This will be a collaborative project involving the Parasitology Section in the School of Veterinary and Biomedical Sciences, the Animal Resources Centre who are providing the scholarship, and the Centre for Microscopy, Characterisation and Analysis, UWA.

Scholarship of $5, 000* available.

 * $3, 000 stipend; $2,000 maintenance funding

 For further information please contact:

Professor Andrew Thompson
Telephone: 9360 2466
Email: a.thompson@murdoch.edu.au

TOP

Investigating the role of lipopolysaccharide (LPS) in the virulence of Brachyspira hyodysenteriae.

The intestinal spirochaete Brachyspira hyodysenteriae is the agent of swine dysentery, a severe mucohaemorrhagic colitis. Not much is known about how this bacterium causes disease, but it is known that surface lipopolysaccharide (LPS) has a part to play in lesion development. In this project you will be isolating and characterising LPS from different virulent and avirulent strains of B. hyodysenteriae, and using these strains and/or the extracted LPS to examine their influence on cultured cell monolayers and/or mice of defined strains that vary in their susceptibility to LPS.

Investigating interactions between intestinal spirochaetes and cultured cell monolayers .

In this project you will be investigating the interactions between intestinal spirochaetes and cultured cell monolayers. This will include an analysis of gene expression by both the spirochaetes and the intestinal cell line in response to their interactions.

Investigating the occurrence and mechanisms involved in gene transfer between intestinal spirochaetes.

In this project you will be looking for evidence of exchange of genetic content between intestinal spirochaetes of the same and different species. You will also be involved in trying to characterise the methods involved, with special emphasis on the role of bacteriophages and novel gene transfer agents.

For more information on the above projects contact:

Professor David Hampson,
Ext: 2287 Room 3.032
Email: D.Hampson@murdoch.edu.au

Salmonella in kangaroos as a risk to children in Perth parks

This project will be run in conjunction with UWA School of Public Health and will involve assessing kangaroo numbers in selected parks in the city, sampling of kangaroo faeces from the parks for salmonellae, fully characterising any Salmonella strains recovered, questionnaire development and application to people using parks, comparison of results with enteric disease databases in the health department etc.

Rickettsial infections in ticks from reptiles in WA

An extensive collection of ticks from reptiles round the State has been established and the project will involve applying molecular techniques to analyse ticks for rickettsial infections, collecting data on ticks from reptiles presented to rescue groups, and comparing sequences from any rickettsiae isolated with currently available information on reptiles from other parts of Australia.

For more information contact:

Dr. Stan Fenwick,
Room 3.031, Tel: (08) 9360 7418
Email: S.Fenwick@murdoch.edu.au

Tick transmitted disease and the role of feral pigs as reservoir species.

Tick transmitted diseases are an emerging public health concern.  Recent research here at Murdoch University has demonstrated the presence of Rickettsia spp. pathogens in ticks obtained from feral pigs.  Large mammals, such as feral pigs, are excellent hosts for adult tick stages and can play an important role in increasing the tick population.  In this project, active tick surveillance, through tick flagging, will be performed in areas with and without feral pig populations to determine if the presence of feral pigs influences the population density of ticks.  In addition, important knowledge regarding the overall population of ticks and the number and distribution of tick species will be obtained.  Finally, PCR-based techniques will be used to test ticks for the presence of potential human pathogens.  This project will involve both field-based and lab-based work components.

For further information contact:

To determine if ecto-parasites (lice, fleas, ticks and mites) found on native animals are infected with Wolbachia.

Wolbachia, belong to the alpha-subdivision of the proteobacteria and are closely related to the Rickettsia and their relatives (Class Alpha-proteobacteria, Order Rickettsiales). Wolbachia are obligate intracellular bacteria transmitted from mother to offspring by infecting the cytoplasm of the egg, however, horizontal transmission has also been recorded. Wolbachia are often described as “reproductive parasites” manipulating the reproductive success of infected females to enhance transmission within a population. The impact of Wolbachia on their host varies. The most common effect is cytoplasmic incapability. Parthenogenesis, male killing, feminisation of genetic males into functional females, enhanced fecundity and fertility have also been attributed to Wolbachia infections. A strain of Wolbachia, called “popcorn” has the potential to reduce the lifespan of arthropods.

This project will contribute to the identification of the Wolbachia spp. in Australian ecto-parasites. Very little is known of the strains of Wolbachia and the relationship of the strains within populations of Australian ecto-parasites.

This project will involve sample collection and identification. Some samples will be provided. Skills gained from this project include sample collection and identification, DNA extraction, PCR, cloning and sequencing as well as phylogenetics. This will be an interesting project collaborating with a group working on Wolbachia in Canada and another group in New York (Jack Werren – the author of many papers on Wolbachia).

Are ticks from Western Australia infected with, Midichloria mitochondrii a unique intra-mitochondrial bacterium?

 This recently discovered novel (alpha-proteobacterial) bacterium Midichloria mitochondrii was first observed in ovaries of female hard ticks, Ixodes ricinus in Europe. A100 % prevalence was found in the female ticks, while a lower prevalence was reported in male ticks. Unpublished data reported a similar bacterium, possibly M. mitochondrii in the Ixodes holocyclus tick from Australia.

In female ticks, the bacterium inhabits the cytoplasm of ovarian cells and possesses the ability to invade and destroy the host's mitochondria. Little is known of the biology of this bacteria or the impact the bacteria has on its host. Initial observations indicate that there is no harm done, in fact, it was hypothesized that the infection may somehow help the ticks.

This project will look at all endosymboints of available Western Australian ticks as well as the intra- mitochondrial bacterium M. mitochondrii.

This will be a very interesting project, which will iclude sample collection and identification, molecular techniques (DNA extraction, PCR, cloning and sequencing) as well as some electron microscope work.

For more information, please contact:

Climate change, rivers and the decline of native freshwater fish

The freshwater fish fauna of the south west of Western Australia is highly endemic, with 80% of species found nowhere else in the world. Unfortunately, it is also in grave danger of extinction, with most species having their range impacted by threats such as climate change, salinisation, river regulation and the introduction of exotic aquatic species. The Fish Health Unit, part of Murdoch University’s Centre for Fish and Fisheries Research, has a number of projects concerned with understanding and preventing freshwater fish declines. All of the projects will involve a combination of fieldwork in streams and rivers throughout the south west, and laboratory studies on fish genetics, behaviour or physiology. The projects include:

1. The effect of introduced parasites on native fish populations. We have recently discovered in native fishes, a number of parasites which have been introduced into Western Australia with exotic aquarium fishes. These parasites appear to be both more prevalent and more virulent in native fish species than in their original host species. Understanding why this is will help us to control them. Are the parasites found more often in native fish habitat? Do the parasites infect native fishes more readily because of the fishes’ behaviour? Are native fishes less able than exotic fishes to mount an effective immune response?
   
   
2. The role of freshwater mussels in maintaining fish populations. The freshwater mussel, Westralunio carteri, has a complex, multi-faceted relationship with native fishes. The first larval stage of the mussel is parasitic in fish gills and fish are therefore essential for completion of the mussels’ life cycle. Mussels may also act as intermediate hosts for a number of trematode parasites that infect fishes. On a more positive note, mussels provide a source of food for fishes and may play an important role in maintaining water quality in the pools in which fishes survive over summer. We know almost nothing, however, about the distribution and life history of freshwater mussels. Where are mussels found? When do they breed? Which fish species act as hosts for mussel larvae? Which fish species eat mussels? How often do mussels and fishes co-occur in summer pools?
   
   
3. Genetic differences between populations of endangered fish. A number of species of native fish have very restricted distributions and recovery plans are being drafted in an attempt to maintain in situ populations of these species. These recovery plans may include captive breeding and restocking to increase population sizes, but before this can happen it is essential that we understand the population genetics of the species concerned. How much genetic variation occurs within and among populations? Is genetic variation sufficiently diminished to constitute a threat to continued survival? Are populations in different rivers sufficiently genetic distinct to warrant their maintenance as separate entities?

For more information contact:

A/Prof. Alan Lymbery
Tel: 9360 2729
Email: a.lymbery@murdoch.edu.au

http://www.vetbiomed.murdoch.edu.au/research/FishHealth/Index.html
http://www.cffr.murdoch.edu.au/

Molecular characterization of Cryptosporidium and Giardia in mussels.

 Giardia and Cryptosporidium areparasites that cause diarrhoea in humans and animals. Theyare transmitted via the faecal-oral route primarily by contaminated food or water and infect the gastrointestinal tract. Although the severity of infection can vary greatly, cryptosporidiosis can be life threatening in immunocompromised patients and there is no effective treatment.

Water is increasingly recognised as an important vehicle for transmission of Cryptosporidium and Giardia. The (oo)cyst is environmentally stable and resistant to inactivation by chlorine at doses commonly used in drinking water treatment.

Bivalves filter large volumes of water and can concentrate Giardia and Cryptosporidium and both parasites have been recovered from numerous species of shellfish. Little is known about the prevalence, geographical distribution of species of Cryptosporidium and Giardia infecting mussels in Western Australia and what the potential health implications are.

The objective of this study is to analyse freshwater mussels from a range of environments (pristine to highly disturbed) in the south west of Western Australia in order to determine (a) the prevalence of Cryptosporidium and Giardia in these mussels using microscopy and PCR and (b) whether human-infectious genotypes of Cryptosporidium and Giardia are found in mussels using PCR and sequencing techniques. This study will therefore provide important information on not only the epidemiology of Cryptosporidium infecting mussels, but will give an indication of the levels of water contamination and will also identify what the public health implications are.

For more information contact: 

Pig nutrition and physiology

Our research group has a number of projects available in the general area of pig nutritional physiology. This is a reasonably broad description of a potential project I recognise, however, if you are interested in any sort of pig research, then feel free to come and talk to me and we can discuss in more detail an area of investigation that will hopefully suit your requirements.

For more information contact:

John Pluske
Tel: (08) 9360 2012
Email: J.Pluske@murdoch.edu.au

Biomechanical analysis of marsupial spines

$2000 scholarship available for student undertaking this project.

The functional demands on the axial skeleton are many and varied. It is an essential organ of both weight bearing and locomotion, and must provide maximal stability while maintaining crucial mobility, in addition to maintaining the integrity of neural structures.

Members of the family Macropodineae (kangaroos and wallabies) constitute the dominant herbivorous fauna of Australia and cover a broad array of terrestrial herbivore niches. The hind limb morphology of macropodines is among the most specialised of all mammals, reflecting their unique method of saltatorial locomotion. Further, craniofacial and appendicular anatomy are known to vary with ecological adaptation in macropods, from arid adapted open plains specialists, through dense understorey inhabitants to the arboreal tree-kangaroos. The axial system, however, is little studied and remains poorly understood in macropods (and in marsupials in general). Being the only large bipedal mammal, in addition to humans, this might lead to some interesting comparisons in form and function.

In this study, you will investigate anatomical, biomechanical and comparative aspects of the axial musculoskeletal system in kangaroos in order to answer some of the following questions:

• How does the musculoskeletal anatomy of the spine of kangaroos reflect the varied demands of weight-bearing and locomotion? 
• Does spinal musculature among different species of kangaroos show patterns of modification that reflect ecological adaptation?
• What skeletal features might be useful in interpreting the ecological adaptation of fossil macropods?    

For more information contact:

Dr Natalie Warburton
Room: VBBS 1.004
Tel: (08) 9360 7658
Fax: (08) 9310 4144
Email: N.Warburton@murdoch.edu.au

Vertebrate Palaeontology - evolutionary adaptations of fossil tree-kangaroos

Macropodoids (kangaroos and their kin) descended from an arboreal, possum-like ancestor in the Palaeogene Period. Following a postulated origin in the middle Miocene (16–11 million years ago), members of the family Macropodineae (kangaroos and wallabies) radiated into a broad array of terrestrial herbivore niches. The hind limb morphology of macropodines is among the most specialised of all mammals, reflecting their unique method of saltatorial locomotion. Given this evolutionary trajectory and the functional–adaptive constraints posed by the terrestrial macropodine bauplan, it is remarkable that one lineage (tree-kangaroos) returned to the arboreal realm during the late Miocene, dispersing into New Guinea before its isolation from the Australian mainland.

Compared with terrestrial macropodines, extant tree-kangaroos (species of Dendrolagus) have a shorter, broader pes characterised by stout tarsal and metatarsal bones. Articular surfaces have been modified for increased flexibility, allowing for greater balance and mobility in an arboreal environment. Species in the extinct genus Bohra have been allied with living tree-kangaroos (Dendrolagus) on the basis of marked similarities in isolated craniodental, forelimb, and hind limb elements. Recently discovered skeletal remains of Bohra illuminata in Pleistocene deposits in caves beneath the central Nullarbor Plain provide the first comprehensive insights into the craniodental and postcranial anatomy characteristic of the genus.

As part of ongoing functional analyses of the postcranial skeleton of the tree-kangaroos, the objectives of this project will be to more clearly detail the key functional attributes of the Dendrolagus hindlimb and to assess the likely arboreal adeptness of Bohra.

For more information contact:

Dr Natalie Warburton
Room: VBBS 1.004
Tel: (08) 9360 7658
Fax: (08) 9310 4144
Email: N.Warburton@murdoch.edu.au

TOP

Evolutionary anatomy of marsupials

The bandicoots are a poorly studied group of marsupials that have a number of unique morphological features of the musculoskeletal system. Together with the marsupial moles, they are the only marsupials to develop an ossified patella and they are also the only marsupials to lack a clavicle. The hand is modified for digging and the morphology of the foot skeleton shares convergent features with both kangaroos and ungulates. In this project you will describe and compare aspects of the musculoskeletal system of the local quenda (southern brown bandicoot).

For more information contact:

Dr Natalie Warburton
Room: VBBS 1.004
Tel: (08) 9360 7658
Fax: (08) 9310 4144
Email: N.Warburton@murdoch.edu.au

Anatomical correlates of synaptic properties in the developing visual cortex

** A $2000 Scholarship is available for students undertaking this project **

Information flow through the cerebral cortex underlies many of the higher brain functions that define human experience – thought, reasoning, sensory perception, emotion. Understanding cortical function requires mapping detailed information about the electrical properties of specific synaptic connections onto the cortical ‘wiring diagram’ provided by anatomical studies.  This project involves using fluorescent and/or confocal microscopy to image and reconstruct fluorescently-labelled, synaptically connected nerve cells in slices of rat visual cortex (see image).  Anatomical properties of these neurons will be correlated with the electrical properties of their synaptic connections, which were measured during electrophysiological recordings conducted at the Laboratory of Molecular Biology (Cambridge, UK). Specific questions that could be addressed in this project include:

1. Does the morphology of synaptically connected neurons in visual cortex differ before and after postnatal eye opening?
   
   
2. Do the morphological properties of synaptically connected neurons differ between different regions of visual cortex?
   
   
3. Are specific morphological features of synaptically connected neurons correlated with the electrical properties of their synaptic connections?

For more information please contact:

Dr Sarah Etherington
Email: s.etherington@murdoch.edu.au
Phone: (08) 9360 6708

Exploring effective treatment strategies for obesity and obesity related disease

Obesity is associated with a cluster of medical conditions (such as type 2 diabetes) that reduce quality of life and burden the public health system. In order to achieve effective treatments for obesity, we need to understand the signals controlling the desire to eat and develop strategies to help combat the desire to eat. Hormones released after food ingestion have now been identified as internal regulators of appetite and have therefore become attractive targets for antiobesity drug development. Since these hormones cannot be absorbed from the digestive system, they are currently administered via multiple injections.
The research objectives of our laboratory are;

1) To develop and assess a novel class of appetite suppressing compounds prepared from these unique hormones, and make them orally ingestible;

2) Identify the target pathways of these hormones;

3) Assess the interaction of these hormones when used in combination with exercise and dietary changes.

The specific honours project will address one of the above stated objectives and will allow you to learn cutting edge techniques and research design. This research project may then be continued into an MSc or PhD.

For further information, please contact:

Timothy J. Fairchild PhD
Senior Lecturer
Faculty of Health Science | Integrated Health Institute
Tel: 9360 2959
Email: T.Fairchild@murdoch.edu.au

HONOURS AND POSTGRADUATE RESEARCH OPPORTUNITIES WITHIN THE PEEL CHILD HEALTH STUDY

'The impact of the environment on children's health'

The Peel children’s health study is a study investigating psychosocial, biological and environmental factors that may impact on child health and wellbeing. Central to the study is the recruitment of a large birth cohort. Between 1600 and 2000 pregnant women will be recruited during their first trimester for this study. This provides an ideal opportunity to investigate very early (pre- and early post-natal) influences on child health. 

For environmental exposures this study will focus on pollutants in and around the home. Environmental data that will be collected includes house dust, air pollutants and various biomarkers of environmental exposures. House dust will be analysed for metals, allergens and, possibly, pesticides. Air pollutants will be measured both inside and outside the home. Finally, maternal and infant blood &/or urine will be analysed for biomarkers of exposure to cigarette smoke, heavy traffic and persistent organic pollutants.
There are a number of opportunities within the Peel study for postgraduate or honours research projects:

1. Interaction of prenatal exposure to indoor air pollutants and indoor allergens on immune responses at birth.

There is increasing interest in the interaction between allergens and other environmental factors on immune responses and the development of allergic respiratory disease in children. Exposure to pollutants and allergens in the indoor environment may be important due to the amount of time people spend indoors, particularly at home. However, there are no data on the impact of prenatal exposure to allergens and pollutants on neonatal immune responses and development of asthma and allergy.

1. to investigate the possible synergetic effects of dust mite allergens and indoor air pollutants on neonatal immune responses, and
2. establish a cohort to investigate the effects of prenatal exposure to HDM and indoor air pollutants on asthma/atopy susceptibility  in childhood.

For this study, dust will be collected from the homes of pregnant women and analysed for house dust mite allergen. Data on indoor pollutants will be collected by questionnaire (type of heating, use of household chemicals, proximity to busy roads) and/or by monitoring. Immune responses will be assessed in blood collected at birth (cord blood).

2. Impact of early life exposure to environmental toxicants (metals, pesticides, persistent organic pollutants) on foetal and infant stress responses.

Exposure to undesirable influences in a child's environment may modify the child's biology through the hypothalamic-pituitary-adrenal (HPA)-axis, the central mediator of the stress response. Both hyper- and hypoactivity of the HPA axis have been associated with such adverse outcomes as cardiovascular disease, behavioural disorders and mental health problems all of which show clear social gradients. As part of the Peel health study HPA activity in pregnant mothers and newborns will be assessed by salivary cortisol and blood catecholamine levels. The aim of the study is to determine the impact of environmental exposure on these measures of HPA activity. Pollutants will be measured in house dust samples (metals and/or pesticides) as well as in the urine or blood (POPs).

3. Impact of environmental pollutants on foetal growth.

There is evidence that environmental pollutants can impact foetal growth and birth outcomes. The most obvious example of this is maternal smoking, which has been associated with low birth weight. There are little data on the effects of other pollutants. In the Peel study, foetal growth will be assessed using ultrasound data collected at 18, 26 and 34 weeks of pregnancy. At birth, body weight and height will define the body mass index (BMI) as an index of physical development and head circumference (HCF) as an index of brain growth. Intra-uterine growth (IUGR) will be measured using existing diagnostic criteria, ultrasound Doppler scans, uterine and umbilical blood flow measures, and new measures of IUGR called proportional of optimal foetal weight (POFW) and optimal birthweight (POBW).

4. Biomarker research.

One of the major difficulties on environmental health research is the assessment of exposure. Exposure assessment is an evolving science and future studies need to consider methods to improve the exposure metric. One area of exposure assessment that has been developing in recent times is the use of biomarkers. The concept has been around for many years, e.g. the use of cotinine as a marker of cigarette smoke exposure. With advances in analytical techniques it is now possible to measure very low concentrations of environmental chemicals or chemical by-products in human tissue and biomarkers of both exposure and of effect are increasingly being used for environmental health research involving air pollutants. However, although biomonitoring offers exciting opportunities, there is still a limited understanding of the relationship between environmental concentrations and biomarkers, particularly for low level exposures that occur in homes. In the Peel study we will be collecting biological fluid (blood and urine) from mothers and infants and this opens the opportunity for research on the relationships between various biomarkers and concentrations of the relevant pollutants in the environment.

The PCHS is funded by the Australian Research Council, The National Health and Medical Research Council of Australia and the Asthma Foundation of Western Australia.

For more information please contact:

Dr Phil Stumbles
School of Veterinary & Biomedical Sciences
Tel: 9360 6201
Email: p.stumbles@murdoch.edu.au

Honours and ISC Projects in the Australian Centre for Necrotrophic Fungal Pathogens (ACNFP)

If you have a genuine and realistic ambition to undertake a PhD in any area of molecular biology, genetics, cell biology, population biology or biochemistry, we invite you to consider Honours or ISC in the ACNFP. The ACNFP, the major national laboratory for the study of necrotrophic fungal plant pathology, is well funded, has access to excellent equipment and is staffed by 8 post-doctoral scientists (7 of whom are full-time in the lab and so can give intensive day by day supervision), with a range of interesting backgrounds, four PhD students and four research assistants.  The essence of Honours is to get training in modern laboratory techniques and experience what it is like to work at the boundaries of science. So even if you have never thought about plants or fungi before, our training could well be what you need. All of our honours students have received 1sts and published in international journals. We work in Molecular Plant Pathology and follow a multidiscplinary approach to dissect the mechanisms by which fungi attack plants and plants resist disease. Current research focuses on the Septoria nodorum wheat pathosystem and necrotrophic foliar pathogens of Medicago truncatula.

 Honours Scholarships are available

1. Analysis of the proteome of a Stagonospora nodorum strain impaired in signal transduction.

Signal transduction pathways are responsible for cellular responses to a variety of stimuli. Disruption of these pathways has many downstream effects including those at the protein level. The aim of this project is to characterise these changes utilising modern proteomics techniques including 2D-PAGE, gel imaging analysis and mass spectrometry to identify specific proteins. This would suit students with interests in biochemistry and microbiology.

2. Characterisation of pathogenicity genes of Stagonospora nodorum on wheat.

Using established transformation techniques, selected genes will be disrupted by insertional inactivation. Mutants will then be screened for and pathogenicity determined using infection assays. Further characterisation of the genes will be also undertaken using a variety of DNA and RNA molecular techniques. This would suit students with interests in molecular biology and genetics.

3. Gene expression during infection of wheat by Stagonospora nodorum.

A major goal of the centre is to identify those fungal genes that are expressed during infection. We have both collections of sequenced genes and unsequenced cDNA libraries prepared from various treatments of the fungus in vitro. Projects will use a combination of microarray technology (we have a G3 at the SABC), RT-PCR and in house bioinformatics to contribute to this goal.

4. Population genetics of Stagonospora nodorum.

S. nodorum is a heterothallic ascomycete fungus i.e. isolates are either “male” or “female”. Ascospores are thought to be important in the establishment of infection at the beginning of the growing season. We have recently determined that although most of the isolates collected as asexual pycnidia are Mat1-1, isolates collected as sexual ascospores are equally distributed between Mat1-1 and Mat1-2.. This is a strange conundrum, which we hope to investigate in this project. The project will involve collection isolates from the wheat belt, mating type testing by PCR and infection assays. This would suit students with an interest in microbiology, population genetics and plant pathology.

5. Mapping disease resistance genes in Medicago truncatula.

We are using the model legume, M. truncatula, to isolate and map genes controlling resistance to a range of fungal pathogens. Projects involve scoring the resistance of progeny of crosses segregating for resistance, the genotyping of progeny using PCR-based markers and the analysis of genetic linkage. Other aspects such as fungal phylogeny and cytology using various microscopical techniques will also be needed. These projects would suit students interested in plant genetics and plant pathology.

TOP

6. Bioinformatic analysis of the Stagonospora genomic sequence.

We have recently obtained the full sequence of Stagonospora.  This is the largest genomics project in the southern hemisphere.  Students with an interest in bioinformatics can engage in projects to analyse and compare the genome with related species.

7.    Generating genetic maps in legumes

Genetic maps are prerequisites for the improvement of crop species by marker-assisted selection.  For legumes, existing genetic maps are very rudimentary.  However we have shown that markers for a model species can be used readily in other species.  Students with an interest in linkage genetics can participate in mapping projects in various legume species.

8.    Investigating the regulation of host selective toxins in S. nororum.

A project is available to investigate the regulation of the toxin ToxA in the pathogenic fungus S. nodorum.  ToxA is small protein that S. nodorum requires for pathogenicity on certain types of wheat.  Whilst studies are currently underway determining the mode of action of the toxin, the external factors influencing expression are unknown .  The expression and activity of the toxin will also be examined in a number of previously created signal transduction mutants.  These signal transduction genes are known to control the expression of many other genes known to be required for pathogenicity and it will be of great interest to determine if they are involved in the expression of the toxin.  Many modern skill and techniques will be used throughout this project including RNA extraction, quantitative PCR using SYBR Green and also advanced molecular mycology methods.

9.    Mechanical barriers and molecular mechanisms that trigger resistance or susceptibility in legumes.

This project will use a range of modern techniques (confocal and fluorescent microscopy and selective staining of leaf sections, qPCR with gene-specific primers) to clarify how fungi penetrate the leaf surface and colonise the plant.  The project involves Chickpea, Field pea, Lentil, Faba bean and Medicago as a model plant for the interaction with A. rabeii, A. lentis, Stago meliloti, A. fabae.

For more information see: The Australian Centre for Necrotrophic Fungal Pathogens Further details from: Dr Peter Solomon, Dr Rob Lee, Dr Huyen Phan, Dr Simon Ellwood, Dr Wenfeng Li, Dr Theo Pfaff and Dr Judith Lichtenzvieg on 9360 7239  or from Professor Richard Oliver on 9360 7404

TOP

WESTERN DAIRY HONOURS PROJECT WITH A DIFFERENCE

• Different because the project is at the specific request of Western Dairy - the regional development program charged with the responsibility of identifying and prioritising Dairy research projects in Western Australia that specifically meet the needs of WA dairy farmers; Different because there is a ready-made, very enthusiastic reference group comprising five dairy farmers, a specialist dairy veterinarian and several leading researchers.
• Different because this Honours project provides a very real opportunity to interact throughout the Australian dairy science community and to develop a career path via a Masters and/or PhD.

TOP

BONE AND MINERAL RESEARCH GROUP HONOURS PROJECTS

CLINICAL STUDIES

Environmental & metabolic influences on muculoskeletal & other diseases in a cohort of elderly women
The aim of this five-year prospective epidemiological study is to determine health outcomes in a cohort of elderly postmenopausal women who were participants of a five-year population based clinical trial of a public health intervention which commenced in 1998. The dietary intervention studied the effect of an increased oral administration of calcium in the prevention of fracture. In this new study we are collecting outcome data in three focus areas, musculoskeletal; cardiovascular and cognitive health, that will allow us to study the effects of parameters already collected including:

• Environmental factors (eg diet, physical activity)
• Anatomical measures (eg bone mass and structure, carotid intimal medial thickness)
• Physiological function (eg mobility, falls risk)
• Metabolic function (eg ApoE levels, hormonal and iron status, homocysteine, beta-amyloid),
• Genetic polymorphisms (eg estrogen receptor, TGF beta, ApoE 4, Cyp19),

These events may predict increased risk of clinical events specifically osteoporotic fracture, cardiovascular events, and neurocognitive function.

RANDOMISED CONTROLLED TRIALS

The Protein Intake Metabolic Effects  (PIMES)  study
The PIMES study is a 2 arm, randomised, double-blind, 2-year study of protein supplementation (30 g/d) versus placebo in 220 women aged over 70 years. The aim of this study is to examine the effects of increased dietary protein intake on sensitive measures of bone structure and muscle mass and body composition in elderly women. We also aim to explore the mechanism of any effects observed. Safety information on the influence of increased protein intake on renal function, and risk factors for cardiovascular diseases arel also being collected.

Arzoxifene Study
The Arzoxifene Study is looking at the effect of Arzoxifene, a SERM, versus placebo on vertebral fracture and invasive breast cancer incidence in postmenopausal women with osteoporosis or low bone density. This double-blind, randomised, placebo-controlled, Phase 3 study is sponsored by the Eli Lilly Company with the trial being managed by Quintiles.

Bazedoxifene Study
Bazedoxifene Study is a study of Fracture Incidence Reduction and Safety of TSE0424 (Bazedoxifene Acetate) compared to Placebo and Raloxifene in Osteoporotic Postmenopausal Women. This randomised controlled clinical trial initiated by Wyeth Pharmaceuticals is designed to examine the relative accuracy of Bazedoxifene, Raloxifene and Placebo on bone related outcomes in particular fracture. The study is now in extension II phase and is Bazedoxifene vs Placebo only.

Zoledronic Acid Study
Zoledronic Acid Study is an evaluation of the safety and efficiency of Zoledronic acid in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D. Novartis Pharmaceuticals has requested the recruitment of 30-40 patients with osteoporosis with or without fracture as part of a multi-centre international study of the effects of intravenous Zoledronic acid on fracture outcomes.

Strontium Study
Strontium Study is examining the normalisation of calcium and vitamin D status and the effects of Strontium ranelate on incidence of new vertebral fractures and peripheral fractures in postmenopausal women.This study is funded by Servier. This study is now in the second extension phase and is open label.

GENOMICS

Role of Aromatase gene on bone structure
Aromatase is the enzyme that manufactures estrogen from precursors, regulation of this gene has strong clinical effects on circulating estrogen levels. We have examined the effects of a polymorphism within this gene and have demonstrated very significant effects on bone density.

Role of the ARHGEF3 gene in osteoporosis
The ARHGEF3 gene plays a role in the reorganisation of the cellular cytoskeleton. We have found strong associations between the ARHGEF3 gene and bone mineral density in women, the details of which have been published in The American Journal of Human Genetics. The mechanism by which this gene can influence bone mineral density is being investigated in our laboratories.

Regulation of filamin genes and relationship to bone and other diseases
Filamin B is a cytoskeleton protein involved in actin polymerisation and participates in its interaction with signal transduction pathways. Rare mutations of the Filamin B (FLNB) gene are the cause of severe health disorders and osteochondrodysplasias including Larsen Syndrome, Boomerang Dysplasia and atelosteogenesis type I & III and this has been confirmed by gene knock-out studies in mice.  We are currently undertaking a detailed study of the effects of common genetic variation in the FLNB gene sequence, which may be expected to have more subtle consequences on bone structure relevant to health of women in the general population.  Thus the aim of this research is to evaluate the role of variation in the FLNB gene in regulating bone mass and the propensity to osteoporotic fracture.

For more information see: Bone and Mineral Research Group