Novel Insights Into The Pathobiology Of Alphavirus Infections
Funder
National Health and Medical Research Council
Funding Amount
$583,477.00
Summary
Ross River virus and chikungunya virus cause muscle and joint pain that can persist for a long time. This project looks at factors in the human host that affect the disease severity, with the aim of finding new treatments.
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.
Discovery Early Career Researcher Award - Grant ID: DE160101574
Funder
Australian Research Council
Funding Amount
$374,360.00
Summary
Understanding the Long-Term Decline in Internal Migration. The project seeks to provide insights into the changing nature of internal migration. Internal migration rates have declined continuously since the 1970s in most advanced economies. This decline in human mobility may affect the functioning of the economy and individuals’ aspirations, but remains poorly recognised and understood. This project aims to establish the onset and pace of the migration decline for a sample of countries. It also ....Understanding the Long-Term Decline in Internal Migration. The project seeks to provide insights into the changing nature of internal migration. Internal migration rates have declined continuously since the 1970s in most advanced economies. This decline in human mobility may affect the functioning of the economy and individuals’ aspirations, but remains poorly recognised and understood. This project aims to establish the onset and pace of the migration decline for a sample of countries. It also aims to identify the causes of this change by identifying linkages between the drop in migration rates and the broader socio-demographic transitions of the past 30 years in Australia, Canada and the United Kingdom. Understanding this issue may support the development of appropriate economic and social policy responses.Read moreRead less
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.
A Place to Call Home: expediting repatriation and ending the practice of warehousing refugees and internally displaced persons (IDPs). Half of the world's 12 million refugees and 25 million IDPs have been living in camps for five to ten years (and longer). The proposed model for refugee and IDP repatriation and reintegration will: significantly increase their human security; alleviate the economic burden on host countries; contribute to the development goals of the countries of origin; facilitat ....A Place to Call Home: expediting repatriation and ending the practice of warehousing refugees and internally displaced persons (IDPs). Half of the world's 12 million refugees and 25 million IDPs have been living in camps for five to ten years (and longer). The proposed model for refugee and IDP repatriation and reintegration will: significantly increase their human security; alleviate the economic burden on host countries; contribute to the development goals of the countries of origin; facilitate the targeting of humanitarian assistance for resolving protracted refugee and IDP situations; and reduce the threats to regional stability. The research will also enhance both Australia's reputation in this humanitarian sector and its institutional capacity to successfully repatriate and reintegrate refugees and IDPs.Read moreRead less
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.
Circular Mobility in Australia: Types, Measures, Patterns and Impacts. The rapid growth of circular mobility (temporary overnight absences from home) for work and leisure reflects newly emerging spatial relationships that trigger massive flux in local populations. This project will: develop new measures that capture the unique dimensions of this movement (frequency, duration and seasonality); show how circulation in Australia varies over time and space; develop model profiles; quantify local imp ....Circular Mobility in Australia: Types, Measures, Patterns and Impacts. The rapid growth of circular mobility (temporary overnight absences from home) for work and leisure reflects newly emerging spatial relationships that trigger massive flux in local populations. This project will: develop new measures that capture the unique dimensions of this movement (frequency, duration and seasonality); show how circulation in Australia varies over time and space; develop model profiles; quantify local impacts; and propose means to accurately estimate service populations. The results will have direct practical application to local authority planning, place the study of circulation on a rigorous analytical footing and enhance international understanding in a field largely neglected hitherto.Read moreRead less
Recycling Endosomes Governing Cell Polarity And Cytokine Secretion.
Funder
National Health and Medical Research Council
Funding Amount
$958,412.00
Summary
Cytokines are chemical messengers released by cells to mount inflammatory responses to fight infections. The timing and direction of cytokine release must be tightly regulated. We investigate the cellular compartments and molecules that control cytokine secretion using sophisticated live cell imaging. Uncontrolled cytokine release is the main cause of ongoing inflammation in arthritis and inflammatory bowel disease and our studies aim to identify cellular targets for new drug development.