Students & Scholarships
Information for Students
Shared supervision and development of multi-disciplinary projects for PhD students at JCU facilitate ready access to expertise and equipment across a diverse range of disciplines. Where possible, PhD students are offered an advisory team that spans at least two of the CBMDT programs, thereby promoting multi-disciplinary research and increasing the impact of publications derived from the work.
Current Postgraduate Scholarship Opportunities
The Australian Institute of Tropical Health and Medicine has a number of PhD scholarships available for outstanding and highly motivated students with an interest in tropical health and medical research, who wish to commence a PhD in 2015.
A sample of CBMDT research projects
This booklet - an extract from a document produced by JCU's Faculty of Medicine, Health and Molecular Sciences - describes 18 research projects supervised by members of the Centre for Biodiscovery and Molecular Development of Therapeutics. The supervisors are Fiona Baird, Jamie Seymour, Norelle Daly, Alex Loukas, Zoltan Sarnyai, Michael Oelgemöller, Patrick Schaeffer and Andreas Lopata.
Current PhD students within the CBMDT
Project: The venom ecology of Conus striatus
Cone snails are venomous predatory marine gastropods which are categorised into three feeding modes. These feeding modes are: vermivorous, molluscivorous and piscivorous. Conus striatus is a piscivorous species found in many tropical and subtropical geographical locations throughout the world. Like all cone snails they use a modified tooth known as a radula which serves both as a harpoon, and a disposable hypodermic needle for venom delivery to acquire highly mobile prey items. This study looked at, not only the venom delivery mechanism of Conus striatus, but also at envenomation site preference and venom efficiency on two sites on the prey item (Chromis viridis). The overall dimensions of the radula were found to be positively related to the cone snail shell length. The average speed of radula extension was found to be 0.00063 seconds and the total envenomation process (radula extension to injection end point) was determined to take, on average, 0.1466 seconds. The cone snail venom concentration was found to be directly related to venom quantity. Envenomation site preference was displayed for the head region of the Chromis viridis. The interplay between all of these elements provides a unique and highly effective mechanism for the delivery of the potent cocktail of conotoxins found in the venom.
Project: The impact of hookworm infection and hookworm anti-inflammatory proteins on diabetes in mice
Type 1 and Type 2 Diabetes Mellitus (DM) are multifactorial diseases with genetic, environmental and immunological aetiologies. People with DM exhibit chronic inflammation and a dysregulated intestinal microbiome characterized by reduced diversity of gut microbiota. Recent research has highlighted that experimental infection of humans with parasitic helminths can alter the microbiota and provide therapeutic benefit in several inflammatory and autoimmune conditions. My Ph.D. project will examine the abilities of helminths and their secreted products to alter intestinal microbial communities, condition the immune system to prevent inappropriate immune responses and restore metabolic homeostasis in murine models of Type 1 and Type 2 diabetes. Identification of these parasite protein and the mechanisms by which they modulate the immune system may facilitate the development of novel biologics for the treatment of diabetes.
Project: Molecular and immunological characterization of Schistosoma acetylcholinesterases and their evaluation as a potential immunogenic vaccine candidates
The nervous system of schistosomes is considered to be an ideal vaccine and drug target. Being acoelomate, schistosome parasites lack a circulating body fluid and hormone-secreting endocrine glands and so rely on their nervous system for a variety of activities that are fundamental to their survival within the host. My research focuses on the molecular and immunological characterization of both tegumental (worm surface) and secreted schistosome acetylcholinesterases (SAChEs), multi-functional enzymes that hydrolyse the neurotransmitter acetylcholine and mediate many other processes essential to parasitism. Specific studies include the knock-out of SAChEs using cutting-edge CRISPR-Cas9 genome editing technology to elucidate the function of these molecules and testing the vaccine efficacy of recombinant SAChEs in models of schistosomiasis infection. If these vaccines prove efficacious, it will have an enormous impact on policy and practice in tropical developing countries, where schistosomiasis is endemic, and improve the health of millions throughout the world’s most disadvantaged communities.
Project: Assessing the anti-colitic properties of the hookworm protein Na-AIP-1
Inflammatory bowel disease (IBD) is an umbrella term for a group of immune-mediated conditions, which are characterised by idiopathic chronic inflammation of the gastrointestinal tract. Current treatment protocols for IBD are often poorly tolerated. A correlation between the decline in prevalence of human parasitic infection and an increase in the occurrence of allergic and autoimmune conditions has been recognised. Various studies have since documented the efficacy of live helminth infection in the alleviation of the signs and symptoms associated with inflammation, in both human and animal models of disease. Despite being well tolerated, numerous hurdles complicate its widespread adoption as a valid anti-inflammatory therapy. As an alternative, the use of immunomodulatory proteins refined from the excretory/secretory (ES) products of anthropophilic helminth species is now being pursued. My research explores harnessing such hookworm ES proteins to treat human inflammatory diseases; specifically, Na-AIP-1, a molecule secreted by the Necator americanus hookworm which I identified in my honours research as having compelling anti-inflammatory properties in murine models of colitis.
Project: Development of disulfide-rich peptides as potential drug leads
Australia has one of the highest rates of prevalence of inflammatory Bowel Disease (IBD) in the world. The two major forms of IBD are ulcerative colitis and Crohn’s disease. There are currently no satisfactory treatments for this set of complex diseases that are estimated to cost 2.7 billion dollars annually in Australia. Estimates suggest that 75,000 Australians have IBD with an expected increase to 100,000 within a decade. Naturally occurring cyclic peptides from plants are emerging as useful templates in drug design because of their stability and ability to adopt non-native sequences. In particular, a cyclic peptide from sunflower seeds, SFTI-1, has been used in the design of novel protease inhibitors and angiogenic agents. In my study, I will use SFTI-1 as a scaffold to design peptides with the potential in treating IBD. Small bioactive peptides, which have been shown to be effective in the treatment of experimental colitis in mice, will be “grafted” into the SFTI-1 framework. Improving the stability of these bioactive peptides by grafting into a cyclic peptide scaffold, such as SFTI-1, may enhance their potency and consequently their therapeutic potential.
Project: Molecular profiling of Immunity to Infectious and Chronic Disease in Humans using Systems Immunology
Infectious and chronic diseases are a major cause of morbidity and mortality worldwide. The development of effective interventions against these diseases is hindered by our lack of understanding of the mechanisms of protective immunity. Until recently, researchers have focused almost exclusively on specific components that form only a small part of the complex host-pathogen interaction network. The recent discipline of systems immunology integrates cutting-edge immunology with ‘omics’ technologies, bioinformatics and computational approaches to understand and predict the outcomes of dynamic interactions in the immune system as a whole. The focus of my project is to employ systems immunology approaches to define the critical immune cells, molecules and signalling pathways required for long-term protective immunity against infectious and chronic disease pathogens.
Project: Innate and adaptive immunity to gastrointestinal helminths
Gastrointestinal helminth infections are an enormous global health problem, with an estimated two billion people infected worldwide, yet they remain neglected tropical diseases. There are currently no vaccines that can limit the burden of these infections, in order to develop such vaccines, more needs to be known about the nature of the innate and adaptive immune responses to these pathogens. My research aims to investigate the molecular and cellular mechanisms of how protective Type 2 immune responses are initiated and regulated following worm infections, particularly the roles of intestinal epithelial cell-derived cytokines and inflammasomes.
Desalegn W. Kifle
Project: Schistosome exosomes-immunobiology and vaccine efficacy
A vaccine for schistosomiasis is desperately required. Countless individuals are infected by schistosomes, and treatment depends entirely on a solitary medication, praziquantel. After curative drug therapy, rapid reinfection occurs, precipitating the need for more rigorous practical control measures, such as vaccination. Proteomic analysis has revealed that extracellular vesicles (EVs) secreted from adult and larval stages of S. mansoni are enriched for vaccine candidate antigens. My study focuses on assessing the roles of S. mansoni EVs in host-parasite communication with a specific focus on the potential vaccine efficacy of EVs and their surface proteins. Gene knockout and silencing technologies will be used to assess the importance of EV surface proteins in host-parasite interactions as a means by which to select key antigens for vaccine development. Recombinant EV surface proteins will be selected for assessment as subunit vaccines in a mouse model of schistosomiasis.
Kieu Thu Le
Project: Identification and molecular characterisation of food toxicology in aquatic products from Vietnam
This project addresses the current situation of food toxins and food allergy in Vietnam. There have been some local studies into the subject but it is rare to find any papers in international publication. The project will begin with a review of the current situation and then investigate toxins of some common seafood species. Another part of this research is collecting the blood serum from people suffering food allergies in Vietnam, comparing with Australian patients, developing antigens, and looking for applications in ongoing studies here in Australia and Vietnam, in terms of public health and food safety.
Project: Development of a mouse model to evaluate the clinical cross-reactivity to the pan-allergen tropomyosin from allergen sources, including shellfish and house dust mite
The muscle protein tropomyosin is the most essential pan-allergen responsible for the cross-reactivity among a variety of invertebrate species. However, there are no published in vivo studies, warranting a detailed analysis of this highly immunogenic protein. My project aims to explore the immunological and subsequent clinical cross-reactivity to tropomyosinin a novel mouse model. This model will allow us to monitor respiratory functions, gastrointestinal inflammatory processes and detail the cellular mechanisms involved in the potential cross-reactivity to TM using different sources such as shellfish and mites.
Project: Curing asthma with human hookworm proteins
Discover the function of the most abundantly secreted proteins from N. americanus and begin to understand how this finely tuned parasite has evolved to modulate/divert the immune response away from a destructive phenotype. Synthetic hookworm proteins will be rapidly produced in cell-free Leishmania ribosomes. Recombinant proteins will be used to assess their anti-inflammatory efficacy in human and mouse in vitro and ex vivo assays, and finally in mouse models of asthma.
Project: Characterisation of the extracellular vesicles secreted by the Schistosoma haematobium and their implication in host-parasite interactions.
The blood fluke, Schistosoma haematobium, infects more than 100 million people throughout Sub-Saharan Africa where it is a major cause of bladder cancer and increases the risk of HIV infection. The mechanisms by which Schistosoma haematobium infects and establishes in the host are not well understood. However, extracellular vesicles (EVs) secreted by the blood fluke Schistosoma haematobium are instrumental in host-parasite interactions, including the establishment of the parasite in the urinary bladder veins. Thus this project is aimed at characterising the EVs secreted by Schistosoma haematobium, evaluating their biological role in the relationship between blood flukes and their mammalian hosts and assessing the vaccine efficacy of the EVs.
Project: Biochemical and Immunological Characterisation of the Major Allergens in Australian Molluscs
Seafood is an increasingly important food allergy worldwide and is typically life-long, affecting about 5% of children and 2% of adults in Australia. This research will characterize allergenic proteins from the shellfish group ‘mollusks’, leading to the design of recombinant proteins. The presence of allergenic proteins will be analysed in mussels, oysters and abalone using genetic analytical approaches. The influence of structure and chemical modifications on the immunoreactivity of mollusc allergens will be studies, thereby providing platform knowledge for better diagnostics and future therapeutics.
Project: Bio-molecular studies on allergenic proteins causing fish allergy in Australian children for improved diagnosis
Fish allergy, part of the current worldwide food allergy epidemic, does not just decrease quality of life: it can be life-threatening. Studies have shown that the prevalence of seafood allergy, including shellfish and fish, is up to 5 % in children and 2 % in adults. Australian/Asian-Pacific fish seem to have unique allergens that are not shared with European fish and have not been well investigated yet. My research aims to identify and characterize those allergens and thereby improve diagnostics and management of fish allergy in Australian children.
Project: High-throughput approach for the screening of Immunotherapeutics in Hookworm Excretory/Secretory (ES) Products
Parasitic infections place a costly and disproportionate disease burden on developing countries. However, evidence suggests that certain parasites, such as hookworms, offer substantial health benefits, particularly in allergy and inflammatory bowel disease. Helminth therapy is gaining momentum and widespread acceptance in the medical community; however, the use of live hookworm therapeutics has drawbacks. An increasing body of evidence suggests that a safer option is to harness the immunomodulatory properties of the hookworms’ excretory/secretory (ES) products. We and others have shown that ES protects against inflammation in several mouse models of colitis, and more particularly that denaturation/digestion of Ancylostoma caninum ES neutralizes its protective properties against inflammation. Recent transcriptional and proteomic profiling of A. caninum has revealed approximately 1500 secreted proteins, among which ~100 proteins were identified in the ES proteome. We have developed a high throughput screening approach using a cell-free protein expression system that rapidly allows us to generate and screen recombinant hookworm proteins for immunomodulatory activity both in vitro and in vivo. Selected proteins will be further expressed in cell-based systems to generate larger amounts for validation and further assessment in different models of chronic inflammation. This study identifies untapped potential for novel hookworm immunomodulatory proteins to be incorporated into the next generation of immunotherapeutics for treating the alarmingly high global burden of inflammatory diseases.
Project: Rational vaccine development for malaria from genomic sequence information
Malaria is a major public health problem, responsible for death of million of people each year. Vaccination has significantly reducing morbidity and mortality caused by infectious diseases. However, there is no effective vaccine for many chronic diseases including malaria. One of the main reasons for the unsuccessful malaria vaccine development is biased and arbitrary selection of antigens. Immunomics is a new approach that selects novel antigens considering the genomics sequence of the etiologic agent, immune response. This approach also uses computer-based algorithms. We hypothesized antigens identified using immunomics approach are excellent targets for development of cross-species malaria vaccine. This project aims to characterize a subset of novel antigens identified from Plasmodium proteome as a key target of protective immune response. A particular emphasis is the identification of Plasmodium antigens that are the target of cross-species protective immunity.
Project: Anti-inflammatory compounds from the hookworm Ancylostoma caninum
Incidences of inflamatory and autoimmune disease are increasing in developed nations due to a lack of exposure to pathogens and parasites such as hookworms. Treatment options for the sufferers of these dieases are limitted. Our laboratory studies the products that the hookworm Ancylostoma caninum produces in an effort to better understand host-parasite biology and to reveal novel therapeutic options for the treatment of inflammatory disease. Evidence from initial screens suggests that low molecular components from this hookworm protect in colitis models. My project focusses on the isolation and characterisation of the small molecules that A. caninum produces that display anti-inflammatory properties. These molecules may have potential to be developed as therapeutic options for the treatment of inflamatory and autoimmune disease.
Project: Current Approaches in diagnosing and managing food allergy among Queensland Public Health settings
Survey health care professional’s perceptions, attitudes, and knowledge regarding treatment of food allergy patients, including Data Coder accuracy and consistency when coding food allergy patients via ICD-10-AM; analysis of north QLD HHS food allergy mortality and morbidity data. Perform ELISA for undeclared allergens in imported packaged foods. A review is to be conducted of north QLD HHS's food allergy policies and procedures and Legislative regulatory compliance Initiatives. These will be assessed as to whether they are reflective of current trends in food allergy research and best practice and whether Queensland Health related documentation contains adequate duty of care to protect food allergy sufferers. We propose that this review will contribute to training tools for health professionals to be implemented in the Northern Clinical Training Network. The culmination of this research is to develop web-based applications that assist health professionals with food allergy diagnosis and treatment, and enhance community awareness via on-line tools.
Project: Analyses of immunological cross-reactivity and molecular differences between parvalbumin, the major fish allergen, from bony and cartilaginous fish species
Healthier lifestyles have seen an increase in consumption of seafood. As a consequence, seafood allergy has also been on the rise. Parvalbumin, the major allergen from fish, is a 12 kDa calcium binding, heat stable protein found predominantly in the muscle tissue of vertebrates. It accounts for up to 90% of fish allergic reactions. Variability of amino acid sequence and IgE-binding sites of parvalbumin across different fish species makes it a difficult target for standardized immunotherapeutics. Therefore, there is a need for development of improved diagnostics and immunotherapy to help aiding better management of fish allergy.
Biyun Sun (HDR student in external collaborating group at Australian Defence Force Academy, UNSW Canberra)
Project: Mononuclear polypyridylruthenium(II) complexes as antimicrobial agents.
Although our di- and oligo-nuclear ruthenium(II) complexes - in which the metal centres are linked by a bridge with a long alkyl chain - have shown significant potential as antimicrobial agents, it is of considerable interest to synthesise related mononuclear ruthenium complexes that also contain the same lipophilic chain in their structure . . . and examine their therapeutic potential. Significantly , these mononuclear ruthenium complexes have shown surprisingly good activity against a number of clinically-important Gram-negative bacterial species. By exploring the antimicrobial properties of the mononuclear ruthenium complexes, including their cellular uptake and intracellular binding sites, we will increase our understanding of the important parameters that govern the biological processing of metal-based drugs, and thereby help guide their future development.
Madhu Sundaraneedi (HDR student in external collaborating group at Australian Defence Force Academy, Canberra)
Project: Oligonuclear polypyridylruthenium(II) and iridium(III) complexes
Given the success of our dinuclear and oligonuclear ruthenium(II) and iridium(III) complexes as antimicrobial and anticancer agents, it is of considerable interest to examine their interactions with nucleic acids and enzymes involved in cell proliferation, both in vitro and in live cells. By exploring these interactions we will increase our understanding of the important parameters that govern the biological processing of the highly-charged and multi-shaped metal-based drugs; and thereby help guide their future development.
Project: Characterization of PEPS and PPDK regulation in bacteria
Phosphoenolpyruvate synthetase (PEPS) and pyruvate orthophosphate dikinase (PPDK) are enzymes which can catalyse the conversion of pyruvate into phosphoenolpyruvate (PEP) and are involved in either gluconeogenesis or glycolysis in some bacteria, protozoa and archaea species. Importantly these enzymes are not present in mammals and therefore may represent an avenue for drug target research. Before this, however, the role and regulation of these enzymes need to be understood. My research is looking at the characterisation and regulation of the activity of PEPS from Escherichia coli, as a general model bacteria,and PPDK from Listeria monocytogenes, the causative agent of listeria.