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Environmental Influences In The Establishment Of The Epigenetic Landscape In Children
Funder
National Health and Medical Research Council
Funding Amount
$695,097.00
Summary
The DNA in each of our cells does not exist alone, it is packaged into complex structures called chromosomes, through association with many different proteins. The distribution of these proteins varies along the length of a chromosome depending on the type of cell and this phenomenon is called 'epigenetics', literally meaning 'above the DNA'. Epigenetic analysis is the study of how proteins and other molecules can change the activity of a gene without changing the DNA sequence. All of our cells ....The DNA in each of our cells does not exist alone, it is packaged into complex structures called chromosomes, through association with many different proteins. The distribution of these proteins varies along the length of a chromosome depending on the type of cell and this phenomenon is called 'epigenetics', literally meaning 'above the DNA'. Epigenetic analysis is the study of how proteins and other molecules can change the activity of a gene without changing the DNA sequence. All of our cells use epigenetic changes to help control how they grow and develop. Evidence suggests a direct link between diet and environmental influences on our epigenetic profile. Recent research has traced the origins of many of the health problems of adult life back to the earliest periods of development _ to the time spent in the womb and the first few years of life. If we are born with a low birth weight, we are more likely to get sick later in life. Overwhelming evidence exists that the environment in the womb is critical for a healthy birth weight (and health in later life) and it is thought that epigenetics may be the missing link between this environment, low birth weight, and therefore health in later life. In addition, mounting evidence supports a general link between epigenetic de-regulation and predisposition to disease. However, the timing and the overall contribution of environmental- genetic influences to the establishment of faulty epigenetic markings remain largely unknown. Twins are the best model to study this link as they share similar (but not identical environments) and some share identical genetic makeup. Using twins, Dr Jeffrey Craig and his team will investigate the factors in the prenatal environment that modify specific cells, leading to low birth weight and increase disease risk later in life. They predict that this occurs via specific changes in gene activity caused by epigenetic disruption.Read moreRead less
Novel Strategies For The Early Identification Provention And Treatment Of The Microvascular Complications Of Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$4,715,000.00
Summary
Despite recent advances, approximately one third of subjects with type 1 diabetes develop kidney disease and similar proportion develop vision-threatening eye disease. Indeed, in many instances eye and kidney disease occur in the same individual. The central aim of this proposed Special Program is the exploration of mechanisms that lead to the development and progression of these devastating complications of type 1 diabetes with a particular focus on novel strategies, directly applicable to man, ....Despite recent advances, approximately one third of subjects with type 1 diabetes develop kidney disease and similar proportion develop vision-threatening eye disease. Indeed, in many instances eye and kidney disease occur in the same individual. The central aim of this proposed Special Program is the exploration of mechanisms that lead to the development and progression of these devastating complications of type 1 diabetes with a particular focus on novel strategies, directly applicable to man, for their prevention and treatment. Participants in Special Program include both established diabetes researchers and investigators from other areas of academia (blood vessel biology and applied genetics). Strong interrelationships between the various investigators and their departments already exist and will be further consolidated with continued collaboration, sharing a combination of models, novel interventions and complex genetic techniques that would not be possible outside of a large collaborative framework. In addition to academic collaboration, interactions with industry-based drug discovery programs is also an important component in developing new treatment strategies for diabetic kidney and eye disease. The Special Program will thus consist of a range of studies of direct relevance to diabetic kidney and diabetic eye disease in humans. It is expected that these studies will lead to new strategies for the prevention, treatment and even the reversal of long term complications of diabetes.Read moreRead less
Transforming Growth Factor Beta Signalling In Malignant Mesothelioma Growth And Collagen Production
Funder
National Health and Medical Research Council
Funding Amount
$509,917.00
Summary
Many cancers contain abundant connective tissue molecules called extracellular matrix (ECM) and data show that interaction of ECM with cells are important in the growth of cancers (1). Changes in expression of ECM and their receptors (integrins) have been associated with malignant changes in cells, enhanced tumour growth and resistance to chemotherapy (2,3). We have recently shown that inhibition of collagen, the most abundant ECM molecule produced by malignant mesothelioma (MM) cells, reduced M ....Many cancers contain abundant connective tissue molecules called extracellular matrix (ECM) and data show that interaction of ECM with cells are important in the growth of cancers (1). Changes in expression of ECM and their receptors (integrins) have been associated with malignant changes in cells, enhanced tumour growth and resistance to chemotherapy (2,3). We have recently shown that inhibition of collagen, the most abundant ECM molecule produced by malignant mesothelioma (MM) cells, reduced MM growth. How cancer cells regulate ECM production and control their growth is unclear but strong evidence suggests the growth factor transforming growth factor-beta (TGFB) plays an important role. We and others showed that MM cells secrete all forms (1-3) of TGFB, and TGFB1,2-like activity has been reported in pleural effusions from MM (4,5). All TGFB forms stimulate MM cells to grow and make ECM (6,7). We showed that high levels of collagen produced by MM are enhanced by TGFB. Small molecules called antisense oligonucleotides (AO) which blocked production of TGFB2 by cells, reduced MM cell growth in soft agar, a characteristic of cancer, and partially blocked MM growth in animal models (4,6). This was supported by studies using soluble TGFB type II receptors, which blocks TGFB1,3 (8), and our studies using TGFB2 specific antibodies, as both studies reduced tumour growth. These findings support a role for TGFB in MM growth. However, all TGFB forms can promote cell grow and collagen synthesis and therefore ways to block all TGFB forms are required to ensure maximal effect. This study will examine the effect of blocking common downstream signalling pathways of all three TGFB isoforms on MM collagen production and tumour growth. These pathways are activated when TGFB binds to its receptors sending messages to the nucleus of the cell to make collagen or grow. By identifying which TGFB signalling pathway is important, we may be able to design novel therapeutic approaches to help treat patients with this disease.Read moreRead less
They aim to create insulin-secreting B cells by identifying their progenitor cells and the moleculaes normally required for their development, in order to restore B-cell function in the people with type 1 diabetes. Mouse and human multipotent embryonic stem (ES) cells and fetal mouse panceas and adult pancreas duct cells will be used as sources of progenitor B cells. Comparative studies will provide a more complete picture of human B-cell ontogeny. Culture systems developed for ES cells-embryoid ....They aim to create insulin-secreting B cells by identifying their progenitor cells and the moleculaes normally required for their development, in order to restore B-cell function in the people with type 1 diabetes. Mouse and human multipotent embryonic stem (ES) cells and fetal mouse panceas and adult pancreas duct cells will be used as sources of progenitor B cells. Comparative studies will provide a more complete picture of human B-cell ontogeny. Culture systems developed for ES cells-embryoid bodies (EB) - EB-derived cells, fetal pancreas and adult pancreas duct cells, will be employed to screen for and identify novel growth-differentiation factors and to optimise parameters for creating B cells in vitro or (re) generating B cells in vivo. Genetic constructs allowing regulated expression of fluorescently-tagged marker genes and growth-transcription factors will be introduced into cultured cells or transgenic mice to enable progenitor B cells to be tracked and isolated. Progenitor B cells will be typed with panels of known novel markers molecules at the gene and protein level, and gene expression profiles of tissue yielding B cells will be analysed across time to reveal further candidate markers. Molecules and methods effective in mouse systems will be applied to human ES cell-derived or pancreatic duct cells. The capacity to progenitor cells or insulin-secreting cells to ameliorate diabetes when transplanted into the testis, under the kidney capsule or into the pancreas of mouse models would represent proof-of-concept. Functional B cells derived from human ERS cells or pancreas duct cells, or growth factors that regenerate B cells in vivo, could together with appropriate immunotherapy restore B-cell function in people with type 1 diabetes.Read moreRead less
Body Composition Changes In Cardiac Cachexia: Pathophysiology, Quantification And Approaches To Therapy
Funder
National Health and Medical Research Council
Funding Amount
$120,000.00
Summary
Cachexia is weight loss and weakness caused by disease, or as a side effect of illness. Congestive heart failure is a common cardiovascular condition that is accompanied by high mortality (up to 50% over 2 years) and considerable suffering. People with congestive heart failure often develop cachexia. This project will explore the mechanisms responsible for the development of cachexia using an animal model of cardiac cachexia that the researchers have developed. It will be complemented by an exam ....Cachexia is weight loss and weakness caused by disease, or as a side effect of illness. Congestive heart failure is a common cardiovascular condition that is accompanied by high mortality (up to 50% over 2 years) and considerable suffering. People with congestive heart failure often develop cachexia. This project will explore the mechanisms responsible for the development of cachexia using an animal model of cardiac cachexia that the researchers have developed. It will be complemented by an examination of the effects of exercise on measures of cachexia in patients with congestive heart failure. The researchers believe that this study will supply valuable new information about the development of cachexia and lead to new therapies for this syndrome.Read moreRead less
Phosphoproteomics: Metabolic And Exercise Signalling Markers For Sedentary And Trained Individuals
Funder
National Health and Medical Research Council
Funding Amount
$1,222,500.00
Summary
It is widely recognized that diet and exercise have a major influence on the health and fitness. Sedentary lifestyles predispose people to obesity and the early development of age onset diseases. In the past decade we have gained considerable insight into the regulatory links between exercise and metabolism particularly involving the AMPK signalling pathway. This project is concerned with the phosphoproteome of trained and untrained skeletal muscle, fat and erythrocytes as a marker of fitness.
Spatial Simulation Modelling Of Containment Strategies For Pandemic Influenza
Funder
National Health and Medical Research Council
Funding Amount
$99,927.00
Summary
This research will develop a spatial simulation model to predict the spread of pandemic influenza within Australia. The resulting software program will be readily usable by disease managers, both during and prior to an outbreak, to predict the effect of various containment measures on the size, rate and location of disease spread, through a city, state or the nation. Deployed in _real time� after an outbreak has started in Australia, it will be used to predict infection spread and the containmen ....This research will develop a spatial simulation model to predict the spread of pandemic influenza within Australia. The resulting software program will be readily usable by disease managers, both during and prior to an outbreak, to predict the effect of various containment measures on the size, rate and location of disease spread, through a city, state or the nation. Deployed in _real time� after an outbreak has started in Australia, it will be used to predict infection spread and the containment effect of a range of interventions. The model would use data obtained during initial stages of the outbreak to refine the model, so allowing accuracy in daily spread prediction; similar use of spatial models occurred during the 2001 Foot and Mouth Disease (FMD) outbreak in the UK. In a pre-pandemic period the simulation model will be available to predict the containment effect of a range of response measures, such as travel restrictions, workplace and school closures, vaccination and antiviral usage. Specifically, this project will apply the simulation model to determine optimal use of limited resources such as the _when and where� targeting of antiviral drugs and initial supplies of vaccine.Read moreRead less
Case Conferencing, Quality Of Life And Palliative Care For Clients From Remote Communities In The Northern Territory
Funder
National Health and Medical Research Council
Funding Amount
$42,750.00
Summary
This project addresses an area in the delivery of palliative care in rural and remote Top End of the NT, where research is seriously lacking. It will focus on the relationship between quality of life and communication between health providers and palliative clients and their carers. The conduit of communication will be case conferences and family conferences. There has been some research that reflects that case conferencing (in urban areas) in palliative care leads to improved quality of life (M ....This project addresses an area in the delivery of palliative care in rural and remote Top End of the NT, where research is seriously lacking. It will focus on the relationship between quality of life and communication between health providers and palliative clients and their carers. The conduit of communication will be case conferences and family conferences. There has been some research that reflects that case conferencing (in urban areas) in palliative care leads to improved quality of life (Mitchell 2006). This project will be assessing whether there is a similar association between quality of life and case conferencing in rural and remote Northern Territory. The project will also assess the dynamics of communication between palliative clients and their carers and the health providers.Read moreRead less
An Exploration Of Functional Decline And The Potential For Rehab In Patients With Advanced Non-small Cell Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$50,000.00
Summary
Lung cancer is one of the commonest human cancers and the leading cause of cancer deaths. People with advanced cancer experience significant decline in functional capacity as their disease advances and they approach death. This decline is likely to have significant impact on quality of life. In lung cancer this decline can be exacerbated by chronic illnesses such as chronic obstructive pulmonary disease (COPD). While significant clinical benefits have been demonstrated in COPD patients with the ....Lung cancer is one of the commonest human cancers and the leading cause of cancer deaths. People with advanced cancer experience significant decline in functional capacity as their disease advances and they approach death. This decline is likely to have significant impact on quality of life. In lung cancer this decline can be exacerbated by chronic illnesses such as chronic obstructive pulmonary disease (COPD). While significant clinical benefits have been demonstrated in COPD patients with the introduction of pulmonary rehabilitation, little research has been conducted to either map the functional status of lung cancer patients or to explore the application of pulmonary rehabilitation in this setting. This study seeks to begin a program of work in this area through first exploring the characteristics of functional decline in this group and then assessing the feasibility and acceptability of a rehabilitation program specifically addressing the functional status needs identified.Read moreRead less
Early Influences Of Obesity And Fat Patterning In Children:critical Periods, Environmental Determinants, And Socio-cultu
Funder
National Health and Medical Research Council
Funding Amount
$1,152,711.00
Summary
Childhood obesity is an escalating public health problem both internationally and within Australia. Rates of childhood obesity in Australia are at one of the highest amongst developed nations. 25% of Australian children are currently overweight or obese. Obesity is a strong risk factor for chronic disease. In children, obesity is of concern because it is highly likely to persist and, during childhood, contributes to serious physical and mental health problems. A quarter of Australian children ar ....Childhood obesity is an escalating public health problem both internationally and within Australia. Rates of childhood obesity in Australia are at one of the highest amongst developed nations. 25% of Australian children are currently overweight or obese. Obesity is a strong risk factor for chronic disease. In children, obesity is of concern because it is highly likely to persist and, during childhood, contributes to serious physical and mental health problems. A quarter of Australian children are now carrying excess body fat. Because of these factors, prevention of obesity is paramount because success of current treatment options is limited and does not last. Especially harmful forms of fatness may originate in early life - the tendency to store fat in the abdominal region and the tendency to accrete fat rather than muscle (at any body size). For this reason, the early life determinants of obesity deserve special attention, even in the presence of society-wide factors conducive to obesity. Professor Moore and a group of researchers from the University of Adelaide will test the proposition that pre-birth and infancy is a ‘critical period’ for the development of obesity. The group aims to investigate whether there is a distinct period in early life for acquiring the predisposition to harmful forms of fatness. The project also aims to identify practical opportunities for prevention, focusing on mothers and their infants.Read moreRead less