Macrophages are important cells at the front-line of immunity where one of their main roles is to release anti-bacterial proteins. We will study the macrophage molecules, subcellular organelles and pathways that help to release these proteins to kill bacteria and fight infection. Our studies will identify new cellular targets for boosting immunity and treating inherited diseases with defective macrophage function.
Macrophages are white blood cells that provide front line defence against infection by initiating inflammatory responses by ingesting or phagocytosing microbes and by releasing soluble messengers (cytokines) to recruit other immune cells. These defensive functions require extensive trafficking of proteins within the macrophages. Protein trafficking is orchestrated in part by a family of membrane fusion proteins called SNAREs. By defining the relevant SNAREs, we have recently discovered a much ac ....Macrophages are white blood cells that provide front line defence against infection by initiating inflammatory responses by ingesting or phagocytosing microbes and by releasing soluble messengers (cytokines) to recruit other immune cells. These defensive functions require extensive trafficking of proteins within the macrophages. Protein trafficking is orchestrated in part by a family of membrane fusion proteins called SNAREs. By defining the relevant SNAREs, we have recently discovered a much acclaimed and novel pathway that allows efficient, combined cytokine secretion and phagocytosis in macrophages. Our studies proposed here will now expand on this discovery by comparing the phagocytic process, in terms of SNARE-mediated membrane and cytokine trafficking, for a wide range of microbes, highlighting differences that could provide new avenues for drug development. Moreover, since our strategy of using SNAREs to investigate and map trafficking pathways has proven so successful, we will now launch a major large-scale initiative to study ALL SNARE-mediated trafficking pathways in macrophages using a discovery pipeline of assays, including live cell imaging, we have developed. This will provide valuable information on many SNAREs including those associated with disease, and will elucidate trafficking pathways governing all macrophage actions in immunity, including cytokine secretion and antigen presentation. All of these pathways are highly relevant to current drug targets being used clinically or studied in inflammatory disease and for the development of vaccines.Read moreRead less
Macrophage Polarisation And Control Of Pulmonary Inflammation.
Funder
National Health and Medical Research Council
Funding Amount
$895,494.00
Summary
As key immune cells, macrophages are polarised to phenotypes that turn inflammation on or off. In cystic fibrosis, defective macrophage polarisation enhances inflammation and prevents lung repair. We are defining the molecules and cellular pathways that control this process and identifying targets for existing drugs that can be used to reprogram macrophages and restore lung repair to improve patient outcomes.
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
Predictors And Correlates Of Health-related Quality Of Life And Morbidity In Overweight/obese Adolescents: Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$512,525.00
Summary
There is now no doubting the size and long-term risks to health of the childhood obesity epidemic. However, very little research has examined at population level its immediate consequences for mental health and physical functioning, what pathways confer risk and protection for these consequences, and their likely healthcare consequences. This study will utilise an existing cohort of approximately 1500 Victorian adolescents followed since childhood to examine neglected aspects of the genesis and ....There is now no doubting the size and long-term risks to health of the childhood obesity epidemic. However, very little research has examined at population level its immediate consequences for mental health and physical functioning, what pathways confer risk and protection for these consequences, and their likely healthcare consequences. This study will utilise an existing cohort of approximately 1500 Victorian adolescents followed since childhood to examine neglected aspects of the genesis and impacts of overweight and obesity. The Health of Young Victorians Study was originally assembled in 1997 when the children were in Grades Prep-3. In addition to information on putative risk and protective factors for overweight-obesity and direct measures of height and weight, it is unique in having collected data on health-related quality of life (HRQoL) since children were first recruited during the early primary school years. Eight years after the first wave, the children will be adolescents in Grades 8-11. This third wave will retain a focus on HRQoL. Innovations include study of potential emotional, behavioural and physical consequences of childhood obesity that may in turn affect the natural history of obesity. This large, population-based longitudinal study will redress neglected aspects of child and adolescent overweight-obesity specifically identified in 2003 by the NH and MRC. As well as establishing whether a range of common problems are related to overweight-obesity, it will be able to shed light on mechanisms of adverse outcomes associated with adolescent overweight-obesity, and study protective factors predicting remitting overweight from childhood to adolescence that may inform preventive activities. The study will make an international contribution to knowledge about pathways, prevalence and preventive opportunities for child and adolescent overweight-obesity.Read moreRead less
DsbA Foldases From Multidrug Resistant Pathogens As Targets For New Antimicrobials
Funder
National Health and Medical Research Council
Funding Amount
$743,401.00
Summary
Bacteria that cause common human infections, such as cystitis and diarrhoea, are now resistant to many antibiotics. If no action is taken, by 2050 antibiotic resistant infections will kill more people each year than cancer. This project aims to address this global public health crisis by characterising promising new bacterial targets and inhibitors designed to disarm multidrug resistant pathogens. Longer term this work could provide new infection therapies that are urgently needed.
A New Master Adaptor Protein For Toll-like Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$869,288.00
Summary
Certain proteins on the surface of cells are able to sense danger and infection. These receptors use adaptor proteins to enable cells to respond appropriately. We have discovered a new adaptor that controls receptor signalling in inflammation. This new master adaptor likely has widespread roles in infection and inflammation. We aim to understand how this adaptor works, and to identify ways of blocking its actions. These studies may help us to control inflammation underpinning many diseases.
Building Capacity For Physical Activity Research In Population Health
Funder
National Health and Medical Research Council
Funding Amount
$2,118,560.00
Summary
The program will focus on the 'diseases of inactivity' and will look at factors like obtaining accurate statistics on rates of inactivity and better statistics on which social groups are least active. It will look at: • the types of activity that are best for different people; • what the best types of exercise programs are; • the types of information campaigns that will be most effective; and • how community amenities and local environments might be used to help people to be active in ways that ....The program will focus on the 'diseases of inactivity' and will look at factors like obtaining accurate statistics on rates of inactivity and better statistics on which social groups are least active. It will look at: • the types of activity that are best for different people; • what the best types of exercise programs are; • the types of information campaigns that will be most effective; and • how community amenities and local environments might be used to help people to be active in ways that are more convenient and enjoyable.Read moreRead less
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).
Innate Immune Signalling In Mycobacterium Tuberculosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$562,857.00
Summary
Tuberculosis (TB) is a major global health threat that causes 1.5 million deaths every year. This study will characterise a new molecular control mechanism that optimises the immune response to the bacteria that cause TB and determine how it contributes to controlling the infection. Such knowledge is essential to help improve patient management and develop better treatments for this devastating disease.