We have discovered a single tumour factor which causes cancer cachexia, a wasting condition that is one of the worst complications of malignancy, for which there is no current effective treatment. We have developed antibodies which effectively block this condition in preclinical models and have produced human/humanised version of this. This application is to characterise these human antibodies to allow us proceed to clinical trials.
Effects Of Replacement And Withdrawal Of Testosterone In Human Males On Muscle, Bone And Fat
Funder
National Health and Medical Research Council
Funding Amount
$156,682.00
Summary
Male sex hormone or androgen deficiency (AD) is a common, but under-diagnosed condition. AD decreases well being and contributes to muscle weakness, bone fragility and weight gain. Cutting edge technology will be used to help explain how AD may relate to these negative effects, particularly on muscle function. Given the importance of aging, frailty, osteoporosis and obesity, understanding the role of hormones in these conditions may have major implications for prevention and treatment.
Many infants and children suffer from bowel motility disorders, for example, chronic constipation affects up to 1 in 10 children. However, the cause of many of these paediatric motility disorders remains unknown. In this project, we will examine the development of wiring of the nervous system that controls bowel motility. This is the first study to investigate the development of cell-cell communication during early stages of nervous system development.
The Role Of Co-signalling Receptors In Cytotoxic Lymphocyte Activity During Infection And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$739,657.00
Summary
Cytotoxic lymphocytes (CLs) are immune cells that detect and kill cancer cells. CLs recognise ‘stress’ proteins on cancer cells through specialised receptors, and this provides the signal for them to kill. However, some cancer cells, such as leukemic cells, can interfere with this recognition to avoid killing by immune cells. This project will investigate the mechanism of recognition and killing of cancer cells by CLs, using both mouse models and cells from patients with acute myeloid leukemia.
The Role Of Stem-progenitor Cells In Regeneration Of Mouse Endometrium.
Funder
National Health and Medical Research Council
Funding Amount
$311,938.00
Summary
The endometrium (lining of the uterus) undergoes breakdown and re-growth each month as part of the menstrual cycle. This restorative process is not well understood. For the first time stem cells have been identified within human endometrium that are likely to be responsible for its remarkable regeneration. The aim of this project is to identify stem cells within the mouse endometrium, to use as a model to understand how the endometrium restores each month after menstruation.
Central Neural Circuits Subserving Nutrient–activated Thermogenesis - The Basis Of Post Prandial Energy Expenditure
Funder
National Health and Medical Research Council
Funding Amount
$766,207.00
Summary
Studies of “energy burning” brown fat, including its importance in the determination of obesity in humans and the potential to increase its capacity by turning white fat into brown-like fat are currently foremost in obesity research. Here we study the detail of brain pathways that dictate brown fat activity after a meal resulting in the burning of ingested calories and reduction of body weight. The results will give us a better idea of how we can harness brown fat to combat obesity.
Central Neural Regulation Of Brown Fat Function – Glucose Sensing And CNS Pathways
Funder
National Health and Medical Research Council
Funding Amount
$761,942.00
Summary
Our research aims to identify how specific brain cells detect changes in glucose levels and how ageing and diet affect their function. We identified a subset of nerve cells that detect changes in glucose and the “hunger” hormone ghrelin, their ability to do so adapting with age and nutritional status. This project will investigate the potential of these nerve cells as targets for therapeutic and diet- intervention strategies to target obesity, diabetes and promote healthy ageing.
Exploring The Therapeutic Potential Of TRAIL In Diabetes And The Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$446,374.00
Summary
TNF-related apoptosis-inducing ligand (TRAIL) is a protein with potentially useful actions in human health and disease. TRAIL is able to prevent atherosclerosis, the cause of heart attacks and strokes. In addition, we have recently shown that its actions on fat and the pancreas may prevent the development of the metabolic syndrome and type 2 diabetes. These studies will explore the therapeutic potential of TRAIL for the prevention of diabetes and heart disease in a range of animal models.
Deadly Commute - Targeting The Trafficking Mechanisms That Licence Inflammatory Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$774,544.00
Summary
MLKL is a protein naturally found inside cells. MLKL is activated by inflammation. Once activated, MLKL relocates to the outer periphery of cells and kills them. Gut cells are especially vulnerable to death-by-MLKL and this problem causes Inflammatory Bowel Disease. Using cutting edge microscopy, we have discovered how MLKL moves to the periphery of cells prior to killing them. We will test if blocking this movement of MLKL to the cell periphery stops gut death and Inflammatory Bowel Disease.