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Linking immunomodulation and latency in alphaherpesvirus infection. Herpesviruses cause major diseases in humans and all domestic animal species. Latency forms a significant part of the evolutionary success of herpesviruses, by enabling transmission of the virus throughout the lifetime of the host. Our work has shown that an alphaherpesvirus protein can divert the host’s immune response to become more antibody-mediated and less T cell-mediated. This study explores the consequences of this immune ....Linking immunomodulation and latency in alphaherpesvirus infection. Herpesviruses cause major diseases in humans and all domestic animal species. Latency forms a significant part of the evolutionary success of herpesviruses, by enabling transmission of the virus throughout the lifetime of the host. Our work has shown that an alphaherpesvirus protein can divert the host’s immune response to become more antibody-mediated and less T cell-mediated. This study explores the consequences of this immune diversion, and examines whether this reduced T cell response enables the development of latent infections. Disrupting the virus-host balance by alterations to this conserved viral protein will enable novel approaches to controlling these economically significant viruses.Read moreRead less
Molecular basis of attenuation in live Mycoplasma vaccines. This proposal aims to use an innovative approach to address an urgent issue raised by the end users of an Australian-owned poultry vaccine with an extensive global market. Recently multiple mutations have been detected in the vaccine re-isolated from vaccinated birds in the field around the world. We will apply a combination of a novel technique for targeted mutagenesis, genome sequencing, and animal experimentations, to address the sig ....Molecular basis of attenuation in live Mycoplasma vaccines. This proposal aims to use an innovative approach to address an urgent issue raised by the end users of an Australian-owned poultry vaccine with an extensive global market. Recently multiple mutations have been detected in the vaccine re-isolated from vaccinated birds in the field around the world. We will apply a combination of a novel technique for targeted mutagenesis, genome sequencing, and animal experimentations, to address the significance of these mutations. Results will improve our understanding of the basis of attenuation of the vaccine, its mechanism of action, and provide commercial confidence in the safety of the vaccine, which is needed to support Australian Universities and Businesses, and the global poultry industry.Read moreRead less
Probing sexual transformation of the human malaria parasite, Plasmodium falciparum, using novel imaging modalities. Malaria parasites adopt a characteristic banana shape prior to sexual recombination; without this shape change disease transmission via mosquitoes cannot occur. This project will use advanced imaging technologies to study sexual recombination of malaria with a view to preventing the millions of deaths due to malaria each year.
Activation of invasion in Toxoplasma. Host cell invasion is critical for the establishment and maintenance of infection by the single-celled parasite Toxoplasma gondii, the causative agent of Toxoplasmosis. This project will use the latest molecular techniques to understand how invasion is activated and will define a new set of drug targets to treat Toxoplasmosis and related diseases.
Signalling pathways for sexual differentiation of apicomplexan parasites. This project aims to study the sexual development of apicomplexan parasites, which cause major diseases in humans, livestock and wildlife, including malaria. Only sexually differentiated cells can survive in the mosquito vector and hence this development is essential for the parasite's life-cycle. This project will employ a new approach that separates female from male parasites, thus enabling new information to be gleaned ....Signalling pathways for sexual differentiation of apicomplexan parasites. This project aims to study the sexual development of apicomplexan parasites, which cause major diseases in humans, livestock and wildlife, including malaria. Only sexually differentiated cells can survive in the mosquito vector and hence this development is essential for the parasite's life-cycle. This project will employ a new approach that separates female from male parasites, thus enabling new information to be gleaned about the development of these parasites. The expected outcomes are an understanding of the mechanisms of sexual differentiation and a functional characterisation of novel sex-specific molecules. This will provide significant benefits, such as pivotal prerequisites for new approaches to parasite intervention.Read moreRead less
Complement evasion strategies of malaria parasites. Pathogens have evolved to protect themselves from deleterious effects of host immune attack. Malaria is one of the most widespread parasitic diseases, yet evasion strategies employed by these parasites are unknown. This project will aim to understand how malaria parasites exploit the innate immune system for successful human infection.
Immuno-epidemiological insights into the development of immunity to malaria and drug resistance. This project aims to better understand the maintenance and acquisition of immunity to malaria in high risk groups. It will also attempt to elucidate how immunity can interfere with the therapeutic efficacy of antimalarials, especially in the assessment of emerging drug resistance. The over-riding hypothesis is that differences in malaria transmission will lead to differential acquisition of immunity ....Immuno-epidemiological insights into the development of immunity to malaria and drug resistance. This project aims to better understand the maintenance and acquisition of immunity to malaria in high risk groups. It will also attempt to elucidate how immunity can interfere with the therapeutic efficacy of antimalarials, especially in the assessment of emerging drug resistance. The over-riding hypothesis is that differences in malaria transmission will lead to differential acquisition of immunity and efficacy of malaria interventions within and between populations. Understanding immunity to malaria is pivotal to develop new interventions, to understand the effectiveness of current malaria treatment and control programs to reduce the global burden of malarial disease.Read moreRead less
Molecular dissection of malaria parasite motility and host-cell invasion across the lifecycle. Malaria parasites move in a unique way, gliding across cell surfaces and infecting host cells using a unique molecular motor. This research aims to understand the molecular mechanics behind parasite movement and use this to develop novel drugs that might throw a spanner in the parasite motor, blocking movement and thereby preventing malaria disease.
Are alternative histones important regulators of transcription in Plasmodium falciparum? Malaria parasites depend on tightly controlled expression of their genes for maintaining infection and causing disease. The project will identify mechanisms of gene control used by parasites; these mechanisms may provide targets for malaria therapies.
Investigating why malaria parasites have a unique translocon. This project aims to explore the mechanism that enables malaria parasites to thrive in their host cells. Parasites that cause the disease malaria reside inside erythrocytes, a very basic cell that lacks a vesicular trafficking pathway. To survive and thrive in this environment, the parasite has evolved a completely unique cell biological phenomenon termed PTEX to transport its proteins into the host cell. The aim of this project is to ....Investigating why malaria parasites have a unique translocon. This project aims to explore the mechanism that enables malaria parasites to thrive in their host cells. Parasites that cause the disease malaria reside inside erythrocytes, a very basic cell that lacks a vesicular trafficking pathway. To survive and thrive in this environment, the parasite has evolved a completely unique cell biological phenomenon termed PTEX to transport its proteins into the host cell. The aim of this project is to determine how this novel PTEX machinery exports proteins into erythrocytes and whether PTEX is also required for parasite survival during the initial stages of a host infection when malaria reside in hepatocytes.Read moreRead less