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Seminal Plasma Cytokines As Novel Fertility Diagnostics In Men
Funder
National Health and Medical Research Council
Funding Amount
$101,000.00
Summary
Infertility and recurrent miscarriage affect 60-80 million couples globally, including 15% of couples in Australia. Current IVF therapy is not successful when the underlying reason for infertility is failure of the maternal tissues to support embryo implantation. We have discovered signaling proteins present in male semen that act in the female reproductive tissues to prepare for embryo implantation and healthy pregnancy. Recently we have identified those proteins and have shown that some men ha ....Infertility and recurrent miscarriage affect 60-80 million couples globally, including 15% of couples in Australia. Current IVF therapy is not successful when the underlying reason for infertility is failure of the maternal tissues to support embryo implantation. We have discovered signaling proteins present in male semen that act in the female reproductive tissues to prepare for embryo implantation and healthy pregnancy. Recently we have identified those proteins and have shown that some men have an imbalance in seminal proteins that leads to immune rejection of the embryo in the female partner. This project aims to develop a new test for male fertility that is based on seminal plasma proteins and independent of existing sperm count tests. Furthermore we will determine whether seminal protein imbalance can result from the �silent� presence of male reproductive tract infection.Read moreRead less
Ocular Implant For The Treatment Of Bacterial Endophthalmitis
Funder
National Health and Medical Research Council
Funding Amount
$483,446.00
Summary
We seek to develop an ocular implant for the treatment of bacterial endophthalmitis. The implant will be a small device that can be administered directly to the affected ocular cavity to release an antibiotic in a controlled manner to clear any infection. The implant will erode and leave no residue. It will be produced from a novel drug-polymer conjugate technology that allows polymer devices that comprise >50% drug to be made.
A Media Formulation To Improve Implantation Rates And Pregnancy Outcome Following ART
Funder
National Health and Medical Research Council
Funding Amount
$304,380.00
Summary
Since women are delaying childbearing, ART is increasingly required. 2-3% of births in Australia follow ART. Only 15-40% of embryo transfers in assisted reproduction (ART) result in ongoing pregnancies. The poor success rate is due to the fact that the embryo culture media bear no resemblance to the maternal environment in which they grow normally. The new culture media to be validated in this proposal includes factors that are critical for embryo implantation and will improve ART success.
Despite recent advances in therapeutic options, chronic viral infections, including infection with hepatitis C virus and hepatitis B virus, continue to be a significant cause of morbidity and mortality in Australia and affecting hundreds of millions of people worldwide. This R&D program aims to develop a cheaper drug formulation that is easier to deliver and more stable for transport to remote areas.
Chronic infections and cancers are major causes of global disease burden. Harnessing the immune system to combat these diseases has proven difficult and cumbersome to date. We invented a new technology to boost the ability of the immune system to fight chronic infections such as AIDS and Hepatitis C. This involves using someone�s own blood treated with sets of short proteins. We term this therapy Overlapping Peptide Pulsed Autologous CelLs (OPAL). This shows great promise in robust animal models ....Chronic infections and cancers are major causes of global disease burden. Harnessing the immune system to combat these diseases has proven difficult and cumbersome to date. We invented a new technology to boost the ability of the immune system to fight chronic infections such as AIDS and Hepatitis C. This involves using someone�s own blood treated with sets of short proteins. We term this therapy Overlapping Peptide Pulsed Autologous CelLs (OPAL). This shows great promise in robust animal models. We now propose to refine this technique in animals in preparation for human clinical trials.Read moreRead less
Novel Silver Nanoparticle Coatings For The Prevention Of Infection Of Biomedical Implants And Devices
Funder
National Health and Medical Research Council
Funding Amount
$455,305.00
Summary
This project targets infections associated with implants and biomedical devices such as catheters, pacemaker leads, knee and hip implants, by the development and evaluation of coatings delivering antibacterial silver ions. The novel coating method is more uniform and reproducible and can be applied to a wide range of biomedical implants and devices. The novel coatings will be tested for antimicrobial effectiveness and safety using cell and tissue culture methods and animal clinical studies.
GM-CSF Regulation Of Preimplantation Embryo Development
Funder
National Health and Medical Research Council
Funding Amount
$481,320.00
Summary
Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be ov ....Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be overcome simply by the transfer of a single embryo. However, patient and clinical expectations are that single embryo transfer should be achieved with little to no reduction in pregnancy rate, and currently this is not possible because our methods for culturing embryos are inadequate. Studies in animals suggest that laboratory growth of mammalian embryos can lead to small-for-gestational age babies (even when the effect of multiple births is taken into consideration). This backed by recent studies which agree that babies born from IVF are smaller than expected. This might lead to health problems in later life, as smallness at birth is associated with higher risks of cardiovascular disease and diabetes, especially as age progresses beyond 40 years. However, the oldest IVF child is currently 23 years of age. Previously we have shown that a protein growth factor, called granulocyte-macrophage colony-stimulating factor (GM-CSF), found normally in the reproductive tract, has dramatic beneficial effects on human and mouse embryos grown in the laboratory. Furthermore, we have shown in mice that embryo exposure to GM-CSF alleviates the detrimental side effects of in vitro culture on foetal growth and body structure after birth. Our research is now focussed on understanding why this protein is beneficial to embryo growth and to test if we can increase pregnancy rates and produce normal healthy infants from the transfer of single embryos treated with GM-CSF.Read moreRead less
Oxidised Mannan As A Novel Adjuvant To Vaccinate Against Mucosal Infections
Funder
National Health and Medical Research Council
Funding Amount
$150,000.00
Summary
Most pathogens invade via the mucosal surfaces. However, current vaccines, which are delivered by injection, are poor at inducing mucosal immunity. An ideal vaccine would comprise a defined protein antigen combined with a suitable adjuvant which could be administered intranasally or orally. Protective antigens have been defined for a number of infections but suitable adjuvants have been elusive. We showed that mannan, a complex carbohydrate from yeast, oxidatively linked to protein antigens can ....Most pathogens invade via the mucosal surfaces. However, current vaccines, which are delivered by injection, are poor at inducing mucosal immunity. An ideal vaccine would comprise a defined protein antigen combined with a suitable adjuvant which could be administered intranasally or orally. Protective antigens have been defined for a number of infections but suitable adjuvants have been elusive. We showed that mannan, a complex carbohydrate from yeast, oxidatively linked to protein antigens can be used as an adjuvant for mucosal IgA and other classes of antibody. Given to mice intranasally, antigen coupled to mannan markedly enhanced production of IgA, IgG1 and IgG2a in serum, and IgA in lung, tears, vaginal secretions, saliva and gut. We have confirmed this for a number of known or putative protective antigens. In addition, both the Th1 and Th2 arms of the lymphocyte response were activated. We have demonstrated protection against P. gingivalis (cause of periodontitis and associated with premature birth and cardiovascular disease) in a mouse lesion model. However, before commercial interests will commit themselves, we need to demonstrate protection against viral infections and in other sites like lungs and gut. Three infection models where IgA has been shown to protect are already set up and can realistically produce results in 1 year. 1. Rotavirus is the major cause of severe infantile gastroenteritis in humans and animals world wide. The latest (live) vaccine was withdrawn because of side effects. We have established a model with Simian rotavirus causing an acute self-limiting disease in infant mice. Adult females will be immunised with mannan linked to killed virus preparations, mated and passive protection of their offspring will be assessed. Preliminary evidence links rotavirus infection with the onset of type 1 diabetes. If this is confirmed, there will be an opportunity to test the vaccine against diabetes. 2. Influenza: IN infection of mice with flu virus is a well established model. Mice will be immunised IN with mannan coupled to haemagglutinin-neuraminidase purified from egg-grown virus. They will be challenged IN with influenza virus and virus titrated in lung homogenates. Neutralising antibody in serum and lung washings will essayed. 3. Respiratory syncytial virus: RSV is the commonest cause of bronchiolitis and pneumonia in infants for which there have been unsuccessful attempts to produce a vaccine. F and G membrane glycoproteins have been shown to protect mice against IN infection, and they will be used coupled to mannan to vaccinate mice against intranasal challenge.Read moreRead less
A New Non-invasive Diagnostic Technique Based On Detection Of Exhaled Respiratory Pathogens.
Funder
National Health and Medical Research Council
Funding Amount
$179,300.00
Summary
We developed a special collection mask and showed that the breath of people with colds or flu contains a tiny amount of virus. Currently, diagnostic samples are collected by putting a tube into the airways - this is very uncomfortable. Our masks may provide a new and more comfortable way to diagnose lung infections. We want to build better masks and ways to detect viruses and bacteria to test out this method. This may create a new test that will improve diagnosis and treatment.
Development And Evaluation Of Novel Antibacterial Coatings For The Prevention Of Infection On Biomedical Devices
Funder
National Health and Medical Research Council
Funding Amount
$284,402.00
Summary
This project aims to develop infection-resistant coatings that can be applied to a wide range of biomedical devices used in human health care. Novel antibacterial compounds from Australian plants (genus Eremophila) will be coated as thin layers onto model materials used for biomedical device fabrication, then onto real-life biomedical products and evaluated for ability to deter colonization by biofilm-forming human pathogenic bacteria.