Crosstalk Between The Repressive Histone Methyltransferases PRC2 And G9A: Structure-function Investigation To Open New Therapeutic Opportunities
Funder
National Health and Medical Research Council
Funding Amount
$595,205.00
Summary
The gene expression programs need to be precisely regulated and the misregulation of these programs can cause a broad range of human diseases. My research will focus on two protein complexes, which heavily contribute to the regulation of gene expression. My study will open a new path for developing new therapeutic strategies.
Spatial And Temporal Dimensions Of Mu-opioid Receptor Signalling: Implications For The Development Of Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$799,316.00
Summary
The use of morphine as an analgesic is still limited by undesirable side effects such as tolerance. Despite decades of research, the mechanisms behind the development of tolerance are poorly understood. The ? opioid receptor is a protein expressed at the surface of the cells that is the target of morphine. This project will investigate the signalling events triggered by opioids with unprecedented resolution and will aim to elucidate why morphine elicits more tolerance than other opioid drugs.
Trafficking Mechanisms Governing Receptor Availability For Signalling
Funder
National Health and Medical Research Council
Funding Amount
$526,978.00
Summary
Receptors on the cell surface allow cells to respond to their environment. We have recently discovered a new pathway for controlling the amount of receptors displayed on the cell surface, errors within which will lead to defects in development and diseases like cancer. We are studying how this new pathway controls the balance between how much receptors are destroyed after being activated and how much are recycled back for re-use.
Molecular Mechanisms Of Receptor Activation And Signalling
Funder
National Health and Medical Research Council
Funding Amount
$571,980.00
Summary
Fundamental to our ability to respond to both immediate and long-term environmental changes and stresses is the coordinated regulation of cellular functions by hormonal and neurotransmitter stimuli. The great majority of such stimuli are sensed by G-protein coupled receptors (GPCR), complex glycoprotein molecules on the surface of most cells that selectively bind and are activated by various hormones and neurotransmitters. Although GPCRs are a superfamily of proteins that now compromise several ....Fundamental to our ability to respond to both immediate and long-term environmental changes and stresses is the coordinated regulation of cellular functions by hormonal and neurotransmitter stimuli. The great majority of such stimuli are sensed by G-protein coupled receptors (GPCR), complex glycoprotein molecules on the surface of most cells that selectively bind and are activated by various hormones and neurotransmitters. Although GPCRs are a superfamily of proteins that now compromise several hundred distinct but structurally-related members, the molecular mechanisms involved in their activation and, thus, their regulation of vital cellular functions, remains unclear. Based on insights that we have gained from the development and characterisation of several alpha1-adrenergic receptor mutants, we have developed a model of receptor activation. In this application we are proposing to further test and to extend the hypotheses underlying this model. Importantly, the functions regulated by GPCR include vital responses, such as the maintenance of circulatory homeostasis by augmenting heart pump function and by constricting vascular smooth muscle to maintain blood pressure. In addition, disordered cellular regulation by GPCR has been implicated in a wide variety of diseases, including hypertension, congestive heart failure and cardiac hypertrophy. Thus, the studies detailed here to further understand the molecular mechanisms of receptor activation have broad implications for our knowledge of critical physiological control systems, and may lead to novel therapeutic approaches to treat a variety of diseases.Read moreRead less
Molecular Pharmacology Of Chemokine Receptor Signalling In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$371,770.00
Summary
Molecular pharmacology is the study of how hormones, neurotransmitters and pharmaceuticals interact with our cells through receptors, which transfer a signal across the cell membrane to change the function of that cell. Chemokine receptors are recognised to play a role in the development of many cancers. Understanding how these receptors work has enormous implications for improving our ability to develop better anti-cancer treatments with fewer side effects.
A Multicentre Randomised Clinical Trial Of Physical Activity For The Treatment Of Patients With Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$773,752.00
Summary
The number of older adults living with Alzheimer's disease (AD) will increase from 26.6 million to 106.2 million by 2050. In the absence of curative treatment options it is important to focus on non-pharmacological interventions such as physical activity. We propose to investigate whether a home-based physical activity program of 24 weeks for patients with AD can successfully decrease the rate of cognitive and functional declince and improve quality of life and psychological well-being.
Understanding And Influencing Physical Activity To Improve Population Health
Funder
National Health and Medical Research Council
Funding Amount
$4,668,376.00
Summary
Three of Australia's leading researchers on physical activity and population health will use new NHMRC program grant funding to consolidate and extend their already internationally-recognised studies. Doing regular physical activity is very important for maintaining good health. It helps to prevent weight gain, type 2 diabetes, heart disease and breast and colon cancer. Unfortunately, most Australian adults are not active enough for health benefits. Rates of overweight and obesity are increasing ....Three of Australia's leading researchers on physical activity and population health will use new NHMRC program grant funding to consolidate and extend their already internationally-recognised studies. Doing regular physical activity is very important for maintaining good health. It helps to prevent weight gain, type 2 diabetes, heart disease and breast and colon cancer. Unfortunately, most Australian adults are not active enough for health benefits. Rates of overweight and obesity are increasing rapidly; more than 50% of Australian adults are above the healthy weight range. Rates of type 2 diabetes have doubled in the past 20 years. New ideas and practical tools are therefore needed to tackle these serious ‘diseases of inactivity’. To this end, Professors Neville Owen, Adrian Bauman and Wendy Brown will bring together innovative and practically useful scientific approaches drawn from psychology, epidemiology and exercise physiology. The approach is interdisciplinary – it combines theories and methods from their individual disciplines in an innovative manner, within a public health framework. Their research to date has developed better methods for measuring people’s exercise habits and has provided new insights into how personal, social and environmental circumstances can make people less active. They have also shown how to design and deliver wide-reaching programs for different social groups and evaluated their effectiveness. Their new research program will build on and significantly extend these ideas and approaches into new areas.For example, they will develop new measures of incidental physical activity and sedentary behaviour and will develop and test new, complex community interventions.Their new program will involve in-depth study of some of the most challenging researchproblems in an important and under-researched area of public health. They will further combine their disciplines and the skills of their research team in new, creative and practical ways, to answer important research questions about physical activity and population health. These ideas and approaches will be used to identify practical ways to help more people to be more physically active.Read moreRead less
Improving Pain And Movement Outcomes In Symptomatic Knee Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
People fear getting painful knee osteoarthritis (OA) more than any other disease – it is seen as progressive and incurable. It often stops people from moving and staying healthy, resulting in an enormous burden on sufferers and the health care system. This program of research aims to understand what brain & nervous system processes might underlie these pain and movement problems and whether new brain-targeting treatment helps. This will allow us to better match treatment to what patients need.
A New Paradigm For Class I Cytokine Receptor Activation
Funder
National Health and Medical Research Council
Funding Amount
$954,946.00
Summary
Class I cytokine receptors include around 30 receptors with diverse functions such as controlling metabolism and inflammation. Cytokine receptors are molecular switches on cells that receive signals from other cells and transmit this signal into the cell’s nucleus to control the regulation of genes. This project will determine the molecular mechanisms involved in class I cytokine receptors and use this knowledge to develop novel ways to modulate these receptors for clinical applications.
Interactions Between RAGE And The Type 1 Angiotensin Receptor Determine The Pro-atherosclerotic Actions Of Angiotensin II
Funder
National Health and Medical Research Council
Funding Amount
$521,956.00
Summary
Heart attacks and strokes are a major cause of death and disability in Australians. Activation of the renin angiotensin system plays a key role in the development and progression of atherosclerosis, the process that leads to narrowing and obstruction of arteries. In preliminary data we have found a way to block these pathways without affecting the control of blood pressure. We believe that interventions based on these data will be important for the prevention and treatment of heart disease.