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Genetic Control Of Susceptibility To Autoimmune Gastritis
Funder
National Health and Medical Research Council
Funding Amount
$346,945.00
Summary
Autoimmune gastritis is caused by the immune system targeting and destroying the stomach lining. We have developed a mouse model of the causes of gastritis and mapped the two major genes that can control susceptibility. This project involves the final stages of identifying these genes and determining how they cause disease.
Functional And Genetic Analysis Of PHF11, A New Gene Associated With Atopic Dermatitis And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$483,261.00
Summary
Atopic dermatitis, or eczema, is an increasingly common severe allergic condition affecting the skin that afflicts up to 30% of all Australian children. Eczema has significant financial impact on families as well on the health and well being of the affected child. The majority of asthmatics are also allergic, explaining why many children who suffer from eczema often go on to develop asthma as well. A familial history of asthma or eczema is an important risk factors for a child developing the dis ....Atopic dermatitis, or eczema, is an increasingly common severe allergic condition affecting the skin that afflicts up to 30% of all Australian children. Eczema has significant financial impact on families as well on the health and well being of the affected child. The majority of asthmatics are also allergic, explaining why many children who suffer from eczema often go on to develop asthma as well. A familial history of asthma or eczema is an important risk factors for a child developing the disorder, meaning that allergy is to a large extent determined by the genes we inherit from our parents. Our genes consist of four different building blocks, called nucleotides, which are identified by four letters: A, G, C and T. Each gene has a specific spelling of these four letters, although between any two people there will invariably be small single letter differences in the way a gene is spelt. Normally, these differences have no effect. In an allergic individual, however, these differences do have an effect. Identifying differences in the way a gene is spelt and why this should lead to eczema or asthma is a major research goal. In the past several years a number of genes have been identified that play an important role in allergy and we have recently identified a spelling difference in a new gene that we believe is important in the allergic response of eczema and asthma. At the moment, we can only guess how this gene might work. We know it is expressed in cells of our immune system that are important in allergy. We also suspect it might be an on or off switch for other genes important for allergy. This project will test these ideas and show how differences in the way this gene is spelt lead to differences in how this gene works. This will be important in adding another piece to the puzzle of how genes control allergy and could lead to better and earlier treatment of these disorders with improved health for affected children as well as adults.Read moreRead less
Fine Mapping And Characterisation Of Polymorphic Immunoregulatory Genes In The Central MHC
Funder
National Health and Medical Research Council
Funding Amount
$529,656.00
Summary
The major histocompatibility complex (MHC) is a group of genes that is usually inherited as a block. The group includes the HLA genes which can serve as markers for neighbouring genes that are less well characterised. For example, some variant forms (polymorphisms) of the HLA genes mark differences in susceptibility to diabetes, lupus and IgA deficiency. We propose that this may be caused by variations in the neighbouring uncharacterised genes affecting control of persistent inflammation of vari ....The major histocompatibility complex (MHC) is a group of genes that is usually inherited as a block. The group includes the HLA genes which can serve as markers for neighbouring genes that are less well characterised. For example, some variant forms (polymorphisms) of the HLA genes mark differences in susceptibility to diabetes, lupus and IgA deficiency. We propose that this may be caused by variations in the neighbouring uncharacterised genes affecting control of persistent inflammation of various target organs. Evidence so far suggests a gene in the central MHC may be responsible. In this project we will study DNA from patients who have unusual combinations of HLA and other MHC genes, to further define which part of the MHC contains the critical immunoregulatory genes. Most genes in the MHC have now been identified by the Human Genome Project, so we will be able to select the most promising candidates in the region of interest. We will then use DNA of known HLA types to determine if the candidate genes vary between individuals. The function of interesting genes will then be investigated by creating cell lines carrying part of the gene in the reverse (anti-sense) orientation. This generates a reverse messenger (m) RNA which binds the normal mRNA and prevents synthesis of the protein. We will then examine which responses of the resultant cell lines are abnormal (eg: production of inflammatory mediators or cytokines). Having elucidated the functions our genes, we will overexpress each version that occurs in patients in cultured cells and look for differences in function. In parallel with this work, we will use laboratory mice with known combinations of MHC genes to establish the effects of particular genes in a live animal.Read moreRead less
Monotreme immune system provides insights into their evolutionary relationships. Genes of immunological importance will be cloned and characterised from the short-beaked echidna with the purpose of investigating the immune system in monotremes, gaining insights into the timing and order of evolutionary separation of the three extant mammalian groups:- the Prototherians (monotremes), the Metatherians (marsupials) and Eutherians (placentals), increasing understanding of the evolution of the verteb ....Monotreme immune system provides insights into their evolutionary relationships. Genes of immunological importance will be cloned and characterised from the short-beaked echidna with the purpose of investigating the immune system in monotremes, gaining insights into the timing and order of evolutionary separation of the three extant mammalian groups:- the Prototherians (monotremes), the Metatherians (marsupials) and Eutherians (placentals), increasing understanding of the evolution of the vertebrate immune system and providing the basis for making immunological reagents which are necessary for studying monotreme diseases (as a precautionary conservation strategy).Read moreRead less
The mucosal immune system of fish: analysis of the immune repertoire in gut-and gill-associated lymphoid tissues in trout. Infectious disease causes major economic loss to the aquaculture industry, highlighting the need for effective vaccination strategies. While oral or immersion vaccination represents the most cost effective means of protecting fish against infectious disease there are problems associated with inducing an effective immune response in fish that will assist our industry partner ....The mucosal immune system of fish: analysis of the immune repertoire in gut-and gill-associated lymphoid tissues in trout. Infectious disease causes major economic loss to the aquaculture industry, highlighting the need for effective vaccination strategies. While oral or immersion vaccination represents the most cost effective means of protecting fish against infectious disease there are problems associated with inducing an effective immune response in fish that will assist our industry partner (Novartis Animal Vaccines Ltd) to develop improved fish vaccines. The project will provide postgraduate training in the area of fish immunology that is vital to the developing Australian aquaculture industry.Read moreRead less
The genetics of resistance to devil facial tumour disease. Tasmanian devils are on the brink of extinction due to a new contagious cancer: Devil Facial Tumour Disease (DFTD). The aim of this project is to determine the genetic nature of DFTD resistance in order to directly contribute to the conservation management of this iconic and ecologically important species. This research will generate fundamental information about genetic diversity in Tasmanian devils and establish the feasibility of bree ....The genetics of resistance to devil facial tumour disease. Tasmanian devils are on the brink of extinction due to a new contagious cancer: Devil Facial Tumour Disease (DFTD). The aim of this project is to determine the genetic nature of DFTD resistance in order to directly contribute to the conservation management of this iconic and ecologically important species. This research will generate fundamental information about genetic diversity in Tasmanian devils and establish the feasibility of breeding resistant animals for release into the wild. Read moreRead less
Functional Genomics to Predict and Enhance Response to Interferon. The increasing number and huge cost impost of new therapies to health providers, both worldwide and nationally, has not yet resulted in a concomitant increase in strategies to optimise their use. Many of the new therapies are proteins (recombinant human proteins or humanised monoclonal antibodies). The improved use of one of Australia's most expensive commonly used protein drugs, pegylated interferon ribavirin (Peg-IFN-R), could ....Functional Genomics to Predict and Enhance Response to Interferon. The increasing number and huge cost impost of new therapies to health providers, both worldwide and nationally, has not yet resulted in a concomitant increase in strategies to optimise their use. Many of the new therapies are proteins (recombinant human proteins or humanised monoclonal antibodies). The improved use of one of Australia's most expensive commonly used protein drugs, pegylated interferon ribavirin (Peg-IFN-R), could potentially produce savings to the Pharmaceutical Benefits Scheme (PBS), and improve delivery of healthcare to thousands of Australians.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668450
Funder
Australian Research Council
Funding Amount
$150,000.00
Summary
Upgrade of comparative phenotypical and functional cell analysis at James Cook University. North Queensland is a fast growing region with significant need for the development of a world-class research facility. James Cook University has recently established the Comparative Genomics Centre at the School of Pharmacy and Molecular Sciences, which will contribute to education and basic research in the region. The research outcomes from the projects of the Comparative Genomics Centre and affiliated l ....Upgrade of comparative phenotypical and functional cell analysis at James Cook University. North Queensland is a fast growing region with significant need for the development of a world-class research facility. James Cook University has recently established the Comparative Genomics Centre at the School of Pharmacy and Molecular Sciences, which will contribute to education and basic research in the region. The research outcomes from the projects of the Comparative Genomics Centre and affiliated laboratories facilitated by the analytical flow cytometer will support the definition and identification of the interactions between genetic and environmental factors in disease and will help to attract researchers. Results from this work will aid the search for therapies for specific health problems.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561251
Funder
Australian Research Council
Funding Amount
$150,887.00
Summary
Facility for Analyses of Evolutionary Immunology. Our understanding of how selection in natural populations shape (favour and disfavour) immunity, and how this process contribute to organismal (including human) fitness, is rudimentary. In order to study such processes our collective experience strongly suggests and increasing need for geographic amalgamation of necessary and complementary molecular and biomedical techniques. We therefore request funding to establish a collaborative research labo ....Facility for Analyses of Evolutionary Immunology. Our understanding of how selection in natural populations shape (favour and disfavour) immunity, and how this process contribute to organismal (including human) fitness, is rudimentary. In order to study such processes our collective experience strongly suggests and increasing need for geographic amalgamation of necessary and complementary molecular and biomedical techniques. We therefore request funding to establish a collaborative research laboratory in a novel research field - Evolutionary Immuno-Ecology- in which all vital aspects, from a mechanistic to an evolutionary level, can be studied at one research centre.Read moreRead less