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
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.
Fall Prevention And Physical Activity Promotion For Older Adults: Cluster Trial Of Effectiveness And Cost-effectiveness
Funder
National Health and Medical Research Council
Funding Amount
$1,291,950.00
Summary
This cluster randomised controlled trial will establish the impact on physical activity and falls of an intervention program that targets both physical activity and falls using assessment, advice and health coaching. The trial will involve 60 established groups of older people, recruited from local chapters of community organisations including Probus, the Older Women’s Network, registered clubs and church groups (estimated average group size of 10; total n = 600).
The Get Healthy Coaching Service To Reduce The Burden Of Low Back Pain: Effectiveness, Cost Effectiveness, And Scalability
Funder
National Health and Medical Research Council
Funding Amount
$1,108,389.00
Summary
Many improve after discharge from treatment for low back pain (LBP), however some experience worsening symptoms and seek costly additional health care. Get Healthy Service® is a free phone-based health coaching service that supports people to remain physically active, however there is no co-ordinated referral pathway to the service. We will test the effectiveness, cost-effectiveness and scalability of a discharge support system linking chronic LBP patients to the Get Healthy Service®.
Scalability Of The Transform-Us! Program To Promote Children's Physical Activity And Reduce Prolonged Sitting In Victorian Primary Schools
Funder
National Health and Medical Research Council
Funding Amount
$549,823.00
Summary
Transform-Us! is an innovative primary school program that has been found to substantially increase children’s physical activity levels, reduce sitting time and benefit health. With simple changes to the school and classroom environments and teaching practices (eg, standing lessons) we will work with partners in the education and health systems to translate this program across Victorian primary schools to determine the real-world implementation and impact of this program over 5 years.
A Scalable Intervention For Increasing Vigorous Physical Activity Among Older Adolescents: The ‘ Burn To Learn ’ Cluster RCT
Funder
National Health and Medical Research Council
Funding Amount
$636,912.00
Summary
Physical inactivity has been described as a global pandemic and only 15% of Australian adolescents are sufficiently active. The pressure to perform in major school assessments drives many older adolescents to sacrifice physical activity to maximise academic performance. Our team has designed a time-efficient solution to increase physical activity in senior high school students using high intensity interval training which will be evaluated using a cluster randomised controlled trial.
Discovery And Mechanisms Of Host Cell Factors In HIV Uncoating
Funder
National Health and Medical Research Council
Funding Amount
$635,098.00
Summary
HIV entry into the host cell involves release of its capsid, a protein shell protecting the viral genome. The capsid hijacks host proteins to cloak itself from cellular defenses while the cell has evolved sensors that can block viral infection. This proposal aims to discover proteins involved in this arms race between host and virus and decipher how they control capsid disassembly. This insight will help design new drugs against HIV infection and new ways to deliver genes for gene therapies.
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
Improving Weight Loss By Intermittent Use Of Very Low Energy Diet: The TANGO Diet Trial (Temporary Phases Of Accelerated Weight Loss For Noticeably Greater Outcomes)
Funder
National Health and Medical Research Council
Funding Amount
$660,736.00
Summary
Very low energy diet (VLED) is being increasingly used for the treatment of obesity, but the resultant weight loss is usually transient, partly because it induces powerful adaptive responses that inhibit weight loss and promote regain. We have shown that 'taking a break from dieting' for 2 weeks reduces these adaptive responses. In this project we will thus test whether weight loss outcomes with VLED can be improved via intermittent use, where periods on the VLED are alternated with 'breaks'.