Through the research supported by this Australia Fellowship, Prof Goulding will recruit and establish an internationally recognized team of researchers to study how nerve cells in the spinal cord function and contribute to the sensorimotor networks that control movement, posture, balance and protective reflexes. Sensory pathways in the spinal cord are important for protecting individuals from tissue damage and noxious insults and they also play an important role in regulating locomotion and move ....Through the research supported by this Australia Fellowship, Prof Goulding will recruit and establish an internationally recognized team of researchers to study how nerve cells in the spinal cord function and contribute to the sensorimotor networks that control movement, posture, balance and protective reflexes. Sensory pathways in the spinal cord are important for protecting individuals from tissue damage and noxious insults and they also play an important role in regulating locomotion and movement. They provide sensory feedback to the motor system to modulate it or activate particular reflexes. A multidisciplinary approach will be taken to dissect these circuits, using cutting edge mouse molecular genetics that allows specialized cell types to be studied and manipulated.Read moreRead less
Functional Copper Deficiency Models Of Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$454,691.00
Summary
Alzheimer's disease is a serious neurodegenerative disease which increases in incidence with age. It affects the quality of life and care required for approximately 160,000 Australians and costs the national economy 6.6 billion dollars per annum. Current therapy is of limited efficacy. Our studies are directed towards testing the hypothesis that a functional deficiency of the essential trace element, copper, occurs in the brain with ageing, and this leads to oxidative stress and death of neurons ....Alzheimer's disease is a serious neurodegenerative disease which increases in incidence with age. It affects the quality of life and care required for approximately 160,000 Australians and costs the national economy 6.6 billion dollars per annum. Current therapy is of limited efficacy. Our studies are directed towards testing the hypothesis that a functional deficiency of the essential trace element, copper, occurs in the brain with ageing, and this leads to oxidative stress and death of neurons associated with Alzheimer's disease. We will use animal and cell culture models to test this hypothesis which is based on promising preliminary data from such models. We believe that beta amyloid, which accumulates in Alzheimer's brains and is believed to be a major part of the pathological mechanism, has a normal role in maintaining copper balance and that this balance is disturbed by ageing or particular mutations. This research should lead to better treatments using drugs which mobilise copper entry into cells.Read moreRead less
Distinct Populations Of Arc NPY Neurons Control Different Aspects Of Energy Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$843,340.00
Summary
Obesity is caused by an imbalance of energy intake and energy expenditure both of which are controlled by specific neurons in the brain. While different types of neurons important in these processes have been identified how they are organised and work in fulfilling the different functions is unclear. Here we aim to identify subpopulations of neurons that are responsible for specific tasks that would make them more specific targets for drug intervention with a reduced risk of side effects.
Obesity-associated diseases are a major health problem and treatments are ineffective. My team’s focus is to determine how a brain molecule called neuropeptide Y (NPY) controls appetite and body fat mass and how this is changed in obesity or in the other extreme, anorexia, which is common in late stage cancer. We will use genetically modified mouse models and investigate the role of NPY under different stress conditions and in cancer. This will tell us if targeting this NPY system with drugs may ....Obesity-associated diseases are a major health problem and treatments are ineffective. My team’s focus is to determine how a brain molecule called neuropeptide Y (NPY) controls appetite and body fat mass and how this is changed in obesity or in the other extreme, anorexia, which is common in late stage cancer. We will use genetically modified mouse models and investigate the role of NPY under different stress conditions and in cancer. This will tell us if targeting this NPY system with drugs may provide a treatment for these diseases.Read moreRead less
Regulation Of Myotubularin Function By The Novel 3-phosphatase Adapter Protein (3-PAP)
Funder
National Health and Medical Research Council
Funding Amount
$488,273.00
Summary
Phospholipids are important components of cell membranes. Phospholipids are turned-on by enzymes called kinases and these phospholipids stimulate a variety of critical functions within the cells. Phospholipids are turned-off by another type of enzymes classed as phosphatases, thereby switching off a broad range of cell functions. Myotubularin is an enzyme, which neutralizes particular type of phospholipids that are involved in the shuttling of proteins between compartments within the cell. Loss ....Phospholipids are important components of cell membranes. Phospholipids are turned-on by enzymes called kinases and these phospholipids stimulate a variety of critical functions within the cells. Phospholipids are turned-off by another type of enzymes classed as phosphatases, thereby switching off a broad range of cell functions. Myotubularin is an enzyme, which neutralizes particular type of phospholipids that are involved in the shuttling of proteins between compartments within the cell. Loss of function of myotubularin, due to inherited genetic changes (mutations), leads to abnormal muscle development manifesting as weakness since birth, and this particular disease is known as 'X-linked myotubular myopathy'. However, there is yet no information on the mechanisms by which failure of protein shuttling (transport) causes myopathy. We have discovered a new protein, 3-phosphatase adapter protein (3-PAP) that links with myotubularin and plays an important role in the function of myotubularin. Our research proposal seeks to clarify the important role of 3-PAP in the development of muscle cells. We propose to study the location of 3-PAP within cells and analyse the influence of 3-PAP on protein shuttling. We have created mice that are deficient in the 3-PAP gene. These special mice will help us understand the importance of 3-PAP in the development and function of nerve and muscle tissue.Read moreRead less
This study combines sophisticated molecular techniques with state-of-the-art biochemical and physiological analyses to determine how gut hormones regulate satiety. By utilising unique conditional and germline KO mice , this research will make highly original and internationally competitive contributions to the understanding of the regulation of satiety and energy expenditure. Knowledge as to the causes of lack of satiety will be of great benefit in the search for novel treatments for obesity.
Control Of Neuropeptide FF Receptors On Appetite And Energy Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$609,281.00
Summary
Despite the alarming obesity epidemic, there currently exists no effective long-term treatment for obesity. Neuropeptide FF and its receptor NPFF2R have an emerging role in regulating food intake and body fat stores. Results from this study will show whether NPFF2R plays an important role in regulating appetite, metabolic rate, body weight and fat stores, thus help to identify whether NPFF2R-targeted therapeutics would confer significant benefit for the long-term treatment of obesity.
The Role Of Neuronal Nicotinic Receptor Subunits In The Self-Administration And Relapse To Alcohol Seeking:Treatments For Alcohol Dependence
Funder
National Health and Medical Research Council
Funding Amount
$531,787.00
Summary
The World Health Organization reports that alcohol causes almost two million deaths every year and results in physical disability or shortened life span for at least 58 million others. Despite the fact that addiction represents more than 40% of brain-related illnesses, there is a dearth of innovative treatments. The overall goal of my research is to develop more effective medications for the treatment of alcohol use disorder by targeting the neuronal nicotinic receptor subtypes that have been sp ....The World Health Organization reports that alcohol causes almost two million deaths every year and results in physical disability or shortened life span for at least 58 million others. Despite the fact that addiction represents more than 40% of brain-related illnesses, there is a dearth of innovative treatments. The overall goal of my research is to develop more effective medications for the treatment of alcohol use disorder by targeting the neuronal nicotinic receptor subtypes that have been specifically altered by heavy alcohol intake.Read moreRead less
Novel Features And Mechanisms Of Congenital Myopathies
Funder
National Health and Medical Research Council
Funding Amount
$464,500.00
Summary
Congenital myopathies are inherited diseases of skeletal muscle that typically present at birth or in early childhood and are characterised by poor muscle tone and muscle weakness. This group of disorders includes nemaline myopathy, central core disease, congenital fiber type disproportion, and myotubular myopathy. All of these disorders are characterised by disorganisation of the sarcomere, the major structure within skeletal muscle cells that is involved in contraction. In addition, the congen ....Congenital myopathies are inherited diseases of skeletal muscle that typically present at birth or in early childhood and are characterised by poor muscle tone and muscle weakness. This group of disorders includes nemaline myopathy, central core disease, congenital fiber type disproportion, and myotubular myopathy. All of these disorders are characterised by disorganisation of the sarcomere, the major structure within skeletal muscle cells that is involved in contraction. In addition, the congenital myopathies have features in common with virtually all muscle diseases such as slow fibre predominance and alterations in contractile force. We are using nemaline myopathy as a representative congenital myopathy to examine features in common amongst the myopathies, characteristic of the congenital myopathies and specific to nemaline myopathy. In nemaline myopathy patients, mutations have been found in five genes that encode proteins of the filamentous systems of the sarcomere. A feature specific to nemaline myopathy is the presence of abnormal structures of the sarcomere called nemaline rods. We have analysed a large number of nemaline myopathy patients that have mutations in the genes that encode the filament proteins alpha-skeletal actin and tropomyosin. In addition, we have generated mouse models for nemaline myopathy and propose to generate an additional one with novel features. Our mouse model has revealed that a feature previously thought exclusive to dystrophies, is also present in nemaline myopathy. The combined analysis of well-characterised patient samples and mouse models will allow us to address longstanding questions about this particular congenital myopathy and myopathies in general. We will determine how rods form and their protein composition. Our mouse models in particular will allow us to address the molecular mechanisms that underpin the increase in slow twitch fibres and the effects that a particular mutation has on muscle function.Read moreRead less