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The Anorexia Of Ageing: Gastrointestinal Control Of Appetite And Feeding In The Elderly
Funder
National Health and Medical Research Council
Funding Amount
$190,500.00
Summary
On current projections, the proportion of the Australian population over 65 years will double to 25% in the next 25 years. Ageing is associated with a reduction in appetite and food intake, which has been called the anorexia of ageing. After about age 70, on average, this is associated with loss of body weight, mainly of muscle. The physiological anorexia and weight loss of ageing predispose to pathological weight loss and malnutrition, which is associated with increased morbidity and death rate ....On current projections, the proportion of the Australian population over 65 years will double to 25% in the next 25 years. Ageing is associated with a reduction in appetite and food intake, which has been called the anorexia of ageing. After about age 70, on average, this is associated with loss of body weight, mainly of muscle. The physiological anorexia and weight loss of ageing predispose to pathological weight loss and malnutrition, which is associated with increased morbidity and death rates. High rates of under-malnutrition have been reported among older institutionalised people in the USA and Australia, with lesser, but still substantial, numbers of community-dwelling older people also undernourished. We found recently that 43% of 250 older recipients of domiciliary care services living in their homes in Adelaide were either malnourished or at risk of malnutrition, and had significantly worse outcomes than their well-nourished counterparts over the following year, including increased falls and hospitalisations. Little research has been done to identify underlying causes and develop treatments for this problem. Recent studies, including ours, have shown that upper gastrointestinal (GI) factors (stomach mechanics, rate of gastric emptying, GI hormones including ghrelin, cholecystokinin [CCK] and amylin) have important effects on appetite and food intake, and are often affected by ageing in ways that reduce food intake The proposed studies will investigate this upper GI control of appetite and its contribution to the anorexia of ageing. We will investigate the effects of ageing on gastric factors, including ghrelin release, the satiating effects of CCK and amylin, and the appetite stimulating effects of ghrelin. The expected outcome of this project is a greater understanding of the causes of the anorexia of ageing, enabling the logical development of effective prevention and treatment strategies.Read moreRead less
Intestinal Adaptation Following Massive Small Intestinal Resection: Mechanisms And Management
Funder
National Health and Medical Research Council
Funding Amount
$256,980.00
Summary
Short bowel syndrome (SBS) remains a major clinical problem in paediatric and adult clinical practice. The Department of Gastroenterology and Clinical Nutrition at the Royal Children's Hospital has gained recognition as a national centre of excellence for the management of infants and children with SBS and intestinal failure. Due to the significant personal and heath-care burden related to SBS there has been an urgent need to improve understanding about the process of intestinal adaptation follo ....Short bowel syndrome (SBS) remains a major clinical problem in paediatric and adult clinical practice. The Department of Gastroenterology and Clinical Nutrition at the Royal Children's Hospital has gained recognition as a national centre of excellence for the management of infants and children with SBS and intestinal failure. Due to the significant personal and heath-care burden related to SBS there has been an urgent need to improve understanding about the process of intestinal adaptation following massive small bowel resection (MSBR) in order to develop new treatments aimed at improving clinical outcome for patients with SBS. Over the past 5 years we have developed a preclinical model for the study of intestinal adaptation in infants using the juvenile pig. Our recent studies in this model have revealed that elemental formula is inferior to whole protein formula suggesting that the current clinical recommendations need urgent re-evaluation. Using the preclinical model in this proposal, we aim to define the mechanisms underlying the adaptive response and evaluate novel therapies aimed at enhancing adaptation following MSBR. Supplementation of enteral feeds with bovine colostrum isolate resulted in normal growth in the preclinical model despite MSBR. In this proposal we plan to advance this observation for the first time to human clinical trials in infants with SBS. Even small gains in enteral tolerance during the early post-operative period may have a significant impact on morbidity and mortality of children with SBS due to parenteral-nutrition related liver disease and gut-related sepsis. This research proposal provides a unique link between studies aimed at providing the scientific basis for understanding the mechanisms of intestinal adaptation using an established preclinical model and translating the results of these studies onto human trials, taking advantage of the clinical expertise available in the management of children with SBS.Read moreRead less
Human ageing is characterised by reduced appetite and food intake, so that average body weight decreases after 70-75 years. This physiological anorexia predisposes to pathological weight loss and malnutrition, worsening of other illnesses, and increased mortality. This project aims to identify causes of this anorexia of ageing, with a view to developing prevention and treatment strategies. We hypothesise that (1) Satiety signals are overactive in the elderly. We will determine whether older peop ....Human ageing is characterised by reduced appetite and food intake, so that average body weight decreases after 70-75 years. This physiological anorexia predisposes to pathological weight loss and malnutrition, worsening of other illnesses, and increased mortality. This project aims to identify causes of this anorexia of ageing, with a view to developing prevention and treatment strategies. We hypothesise that (1) Satiety signals are overactive in the elderly. We will determine whether older people are more sensitive to gastric distension, which reduces appetite and food intake, by measuring perceptions (fullness, hunger, etc), gastric compliance and food intake during intragastric balloon inflation. This will also be done during nutrient infusion into the small intestine, to assess the interaction between gastric and intestinal satiety factors. The contribution of age-related slowing of gastric emptying to the anorexia of ageing will be assessed and the possibility that reduced energy intake worsens the anorexia of ageing will be examined in a nutrient supplementation study. We will have shown that the release of the satiety hormone cholecystokinin (CCK) is greater in older than young adults and that CCK administration causes a greater suppression of food intake in older people, suggesting that increased CCK activity may be a cause of the anorexia of ageing. We will pursue these findings by attempting to increase appetite and food intake in the lderly by administration of a CCK antagonist (blocker). We will also measure the satiating effects of two other probable satiety hormones, amylin and glucagon like peptide 1 in older and young people. (2) The feeding drive is reduced in the elderly Opioids stimulate feeding. In animals this effect is reduced by ageing. To determine whetther this is also so in humans, the suppressive effect of the opioid antagonist naloxone on feeding will be assessed in young and older subjects.Read moreRead less
The Role Of A Low Emulsifier Diet To Treat Crohn's Disease
Funder
National Health and Medical Research Council
Funding Amount
$447,603.00
Summary
Currently, there are no specific diets known to treat Crohn’s disease (CD). Initial lab- and animal-based studies have indicated emulsifiers added to food drive inflammation in CD, but no human trials completed. This study will design and feed high and low emulsifier diets to healthy and CD subjects and measure markers of inflammation. This will establish the role of a low emulsifier diet to treat CD.
Genetic Validation Of Stat3 As A Tractable Pharmacological Target In Gastrointestinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$586,964.00
Summary
Cancers of the stomach and the colon are a major health burden. One of the central signaling molecules that drives these cancers is called Stat3. Here we propose to use a novel strain of mice that allows us to experimentally dial down the amount of Stat3 protein and hence to predict how effective a future anti-Stat3 cancer drug will be.
Bacterial pathogens are a major cause of illness and death, producing diseases ranging from acute infections to cancer. However, not all infected individuals will succumb to these pathologies. What factors dictate which individuals develop these diseases is an important complex question. The core focus of my research is the identification and characterisation of novel host factors that are involved in resistance or susceptibility to bacterial-associated diseases of the gastrointestinal tract.