Identifying Novel Lipid And Genetic Signatures Of Metabolic Disease In Early Childhood
Funder
National Health and Medical Research Council
Funding Amount
$354,592.00
Summary
Both our genetic makeup and environment can contribute to the development of obesity, diabetes and heart disease. Although onset usually occurs in adulthood, the progression towards disease can start in early life. Early childhood represents an opportunity for intervention to avoid adverse health outcomes in adulthood. This proposal combines two established birth cohorts from Singapore (GUSTO) and Australia (BIS) to examine the genetic and environmental origins of metabolic diseases.
The Management To Optimise Diabetes And MEtabolic Syndrome Risk Reduction Via Nurse-led Intervention (MODERN) Study
Funder
National Health and Medical Research Council
Funding Amount
$1,445,861.00
Summary
There is increasing recognition of society’s responsibility to provide effective and sustainable health care to the entire population and not just selected parts. This practical study will test the impact of a nurse-led, multidisciplinary prevention program to reduce the risk of future cardiovascular events in middle-aged individuals at a high risk of developing cardiovascular disease (CVD) living in regional Australia.
Targeted Development Of AMPK Β2-isoform Allosteric Activators
Funder
National Health and Medical Research Council
Funding Amount
$898,147.00
Summary
Sedentary lifestyles and consumption of high energy foods has led to dramatic increases in the incidence of diseases associated with metabolic dysregulation e.g. type 2 diabetes. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK) which functions as a cellular fuel gauge. We have discovered a new drug that crucially activates the form of AMPK found in metabolically active organs. We aim to develop this drug to unlock new therapeutic opportunity.
Targeting The Sympathetic Nervous System To Reduce The Burden Of Fatty Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$728,152.00
Summary
The metabolic syndrome is characterised by abdominal obesity, high blood pressure and an increased risk of diabetes development. It is clear from our own observations that the sympathetic nervous system (SNS) is important in the generation of obesity-related illness and, through its stimulation of the liver, plays an important role in the development of obesity-related liver disease. We will target the SNS in order to reduce the burden of obesity-related liver disease.
Determination Of Irradiation Dose Efficacy For Use In Impaction Grafting At Revision Joint Replacement
Funder
National Health and Medical Research Council
Funding Amount
$411,517.00
Summary
Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence ....Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence of early complications of this procedure have included loss of fixation within the bone. Fracture of the bone around prostheses has also reported in some centres. These events require more surgery, putting the patient at higher risk greater complications and longer rehabilitations. Recent improvements in surgical technique and donor bone preparation have improved results. A current debate questions whether the dose of irradiation can be reduced from 25 kGy, while maintaining sterility of allografts. The risk of bacterial contamination in allografts is low, and irradiation reduces the mechanical strength of the graft, contributing to complications when irradiated bone is used. The benefits of decontaminating the bone may be outweighed by the higher risk for failure due to poor bone quality and resulting prosthesis instability. We will use ISO standards to test the validity of radiation dose for sterilising bone ex vivo. In the absence of controlled human studies, our aim is also to compare the results of impaction grafting with non-irradiated bone versus bone irradiated at current doses used by Australian bone banks, and lower doses indicated by ex vivo testing. We will use a large animal model of revision hip replacement, with precise measures of prosthesis stability. The results of this study will guide clinical decisions regarding the efficacy of current bone graft preparation procedures and the use of irradiated bone in human hip replacement surgery.Read moreRead less
Role Of IGF Binding Protein-3 (IGFBP-3) And IGFBP-5 As Modulators Of Nuclear Hormone Signalling
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain ....The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain cells perform specialised functions. In test-tube experiments, IGFBP-3 and IGFBP-5 interact directly with the receptors that regulate the effects of these hormones. If the same thing happens inside the cell, IGFBP-3 and IGFBP-5 could change the way these receptors respond to signals from outside the cell. We will investigate what effect these IGFBPs have in living cells and in whole animals and how this may relate to human disease. If we are able to understand how IGFBP-3 and IGFBP-5 affect the way cells respond to vitamin A and D, then we may be able to develop new ways to treat certain human diseases.Read moreRead less
Metabolic Stress Sensing By AMPK: Implications For Energy Balance And Isoform-targetting Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$632,188.00
Summary
Metabolic diseases such as obesity, type 2 diabetes and cardiovascular disease impose enormous medical and economic burdens on Western societies. Our research is focussed on the enzyme AMP-activated protein kinase (AMPK) which acts as the fuel gauge of the cell and is a promising drug target for combating metabolic diseases. Our discoveries provide critical insight on how AMPK is switched on by both energy demand and drugs, and will greatly assist development of AMPK-targetted therapeutics.
Regulation Of Protein Kinases And Their Substrates
Funder
National Health and Medical Research Council
Funding Amount
$582,000.00
Summary
Western communities are experiencing an obesity epidemic with up to half the population being overweight. Sedentary life styles and high caloric intake are the cause and will contribute to the development of age onset diseases including obesity, diabetes, cardiovascular disease, stroke and neurodegeneration. This project is investigating an enzyme that plays a pivotal role in controlling the body s response to exercise and diet. The key enzyme involved in this process is called the AMP-activated ....Western communities are experiencing an obesity epidemic with up to half the population being overweight. Sedentary life styles and high caloric intake are the cause and will contribute to the development of age onset diseases including obesity, diabetes, cardiovascular disease, stroke and neurodegeneration. This project is investigating an enzyme that plays a pivotal role in controlling the body s response to exercise and diet. The key enzyme involved in this process is called the AMP-activated protein kinase. This work will increase our understanding of the health benefits of diet and exercise. This new knowledge will play a vital role in developing new therapies for promoting exercise and mitigating the effects of diet that will improve health during the ageing process.Read moreRead less
G Protein-Coupled Receptors (GPCRs) form the largest family of receptors and drug targets in living organisms. Currently, the major reason that new drugs fail to reach the clinic is lack of appropriate drug effect (approx. 30%). Thus, we need a better understanding of how GPCRs work and how this relates to disease. Work within my fellowship will address this knowledge gap, using GPCR models that are relevant to treatment of metabolic, inflammatory, cardiovascular and central nervous system disea ....G Protein-Coupled Receptors (GPCRs) form the largest family of receptors and drug targets in living organisms. Currently, the major reason that new drugs fail to reach the clinic is lack of appropriate drug effect (approx. 30%). Thus, we need a better understanding of how GPCRs work and how this relates to disease. Work within my fellowship will address this knowledge gap, using GPCR models that are relevant to treatment of metabolic, inflammatory, cardiovascular and central nervous system disease.Read moreRead less
The Role Of Osteocytes In Particle Induced Osteolysis
Funder
National Health and Medical Research Council
Funding Amount
$457,196.00
Summary
Hip replacements often fail due to the loss of adjacent bone. Metal or polyethylene particles are produced as the prosthesis bearing surface wears but how do these particles lead to bone loss? Our work suggests involvement of osteocytes within the bone mineral, which are increasingly understood to drive bone physiology and pathology. We will explore the role of the osteocytes by examining their response to particles, which may identify a new target to prevent particle-induced bone loss.