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.
Transgenerational Effects Of Male Obesity - Mechanisms And Interventions
Funder
National Health and Medical Research Council
Funding Amount
$829,143.00
Summary
Childhood obesity is associated with obesity in either parent, and obese children tend to become obese adults, forming an intergenerational cycle that promotes obesity. We have identified paternal obesity as an important novel target for intervention to stop the progression of the obesity epidemic. This project investigates supplementation of obese fathers with folate to prevent the adverse impact of paternal obesity on subsequent generations.
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.
Deciphering The Transcriptional Program That Instructs Lymphatic Endothelial Cell Fate.
Funder
National Health and Medical Research Council
Funding Amount
$541,950.00
Summary
Lymphatic vessels are essential to maintain fluid balance in most tissues of the human body. Further the lymphatic vasculature plays a central role during cancer and contributes to tumour metastasis. Despite this integral function in health and disease little is known about the molecular programs that coordinate gene expression to build a functional vasculature. This research project will address this gap in our knowledge and will open up new therapeutic avenues for lymphatic vascular disorders
Touch and Tension: Molecular Determinants of Human Mechanosensation . Feelings of touch and muscle tension are initiated by mechanosensory neurons found within the peripheral nervous system. Knowledge of human mechanosensory neurons has predominantly relied on rodent studies because of the limited availability of human tissue, which is not ideal. Our team has developed novel technologies for generating human mechanosensory neurons ‘in the dish’. The major aim of this project is to use human stem ....Touch and Tension: Molecular Determinants of Human Mechanosensation . Feelings of touch and muscle tension are initiated by mechanosensory neurons found within the peripheral nervous system. Knowledge of human mechanosensory neurons has predominantly relied on rodent studies because of the limited availability of human tissue, which is not ideal. Our team has developed novel technologies for generating human mechanosensory neurons ‘in the dish’. The major aim of this project is to use human stem cell-derived mechanosensory neurons as a platform to extensively study their molecular and functional properties. The significant benefits are the advancement of knowledge in the human mechanosensory system, which to date has been lacking, and in the long-term progress commercial development of novel drugs.Read moreRead less
Dual Targeting Of The Androgen Receptor For Effective And Durable Control Of Lethal Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$946,177.00
Summary
Preventing binding of androgens to the androgen receptor is the mainstay treatment for advanced prostate cancer, but resistance inevitably develops and the disease becomes lethal. We will develop a new drug that targets a part of the androgen receptor unrelated to its androgen binding function to overcome resistance to current therapy. As this drug will be effective in all stages of prostate cancer, it has high potential to improve survival outcomes for men with prostate cancer.
Pressures Exerted On Upper Airway Walls By Surrounding Tissue Structures
Funder
National Health and Medical Research Council
Funding Amount
$426,500.00
Summary
The obstructive sleep apnoea syndrome (OSA) refers to a condition in which throat blockage occurs during sleep leading to breathing difficulties, including cessation of breathing for short periods of time. OSA effects both men and women but is amongst the commonest of chronic disorders of adult males, occurring in 5% of men over the age of 45 years. In the proposed studies we will examine the effect of the pressure in the tissues surrounding the throat on the ability of the throat to stay open a ....The obstructive sleep apnoea syndrome (OSA) refers to a condition in which throat blockage occurs during sleep leading to breathing difficulties, including cessation of breathing for short periods of time. OSA effects both men and women but is amongst the commonest of chronic disorders of adult males, occurring in 5% of men over the age of 45 years. In the proposed studies we will examine the effect of the pressure in the tissues surrounding the throat on the ability of the throat to stay open and allow breathing. The major outcome of the animal studies is increased knowledge concerning mechanisms whereby collapsing forces are applied to the upper airway. This will give insights into potential factors influencing upper airway collapse during sleep in OSA patients. Of particular importance will be our studies on the effects of jaw position on the pressure exerted on the walls of the throat since the use of an intra-oral device to hold the jaw forward during sleep is one of the treatments used to prevent throat blockage during sleep. The studies in humans will examine, for the first time, the notion that the mass (weight) of the neck has a direct effect on the severity of sleep disordered breathing. If neck mass has a substantive influence on sleep disordered breathing then strategies aimed at reducing neck mass (fat) may provide a new therapeutic approach to the management of OSA patients.Read moreRead less
BioPolymer Fibres For Remodelling Mdx And Damaged Muscle
Funder
National Health and Medical Research Council
Funding Amount
$527,286.00
Summary
This project aims to generate new, smart polymers for use in re-building muscle that has degenerated due to disease and-or trauma damage. The merger of smart polymers with biologically based solutions and cells has great potential to improve outcomes of treatments of damaged muscle in diseases such as Muscular Dystrophy.
Molecular Regulation Of Metabolism And Body Composition By Ski Via Crosstalk With Nuclear Hormone Receptor Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$558,441.00
Summary
Obesity is a common and burdensome health problem in the community which leads to diabetes and heart disease. A number of factors, including hormones play important roles in determing risk of obesity. This study proposes to investigate whether the Ski gene which is a regulatory factor for many hormones affects metabolism in transgenic mouse models of altered Ski function. The proposed studies may identify Ski as a target for therapy for obesity and improvement in sketal muscle metabolism.