Regulating The Secretion Of Inflammatory Cytokines
Funder
National Health and Medical Research Council
Funding Amount
$558,441.00
Summary
Cytokines or chemical messengers released by cells are essential for controlling immune responses but, in excess, they cause Crohn's disease and arthritis. Our research aims to block cytokine release as a novel way to ameliorate disease. We have identified specific cellular proteins, called golgins, that can be targeted to reduce cytokines. Here, characterization of golgin mediated cytokine transport in cells and in a mouse disease model is necessary to translate these findings for human benefit
History in their bones: A diachronic, bioarchaeological study of diet, mobility and social organisation from Cambodian skeletal assemblages. Australia will further enhance its role as an innovator in the archaeology of SE Asia through this cross-disciplinary, international collaboration on the mobility, health, age and diet in ancient Cambodia. Local collaborations will be expanded and academic and cultural relations with Cambodia will be reinforced and strengthened. This research will expand ....History in their bones: A diachronic, bioarchaeological study of diet, mobility and social organisation from Cambodian skeletal assemblages. Australia will further enhance its role as an innovator in the archaeology of SE Asia through this cross-disciplinary, international collaboration on the mobility, health, age and diet in ancient Cambodia. Local collaborations will be expanded and academic and cultural relations with Cambodia will be reinforced and strengthened. This research will expand understanding of Cambodian history and underscore its pivotal role in mainland SE Asian archaeology. Australia's advancement of knowledge about Cambodia's rich cultural antiquity will be recognized worldwide by a global community acutely mindful of the losses to culture and heritage endured by Cambodia in the recent past.Read moreRead less
Agriculture and the Late Bronze Age collapse of the Hittite Empire. National benefit will be accrued through the major scholarly contribution the project makes to a key debate in world archaeology, namely the extent to which environmental change affected ancient complex societies, especially climate change. As such it fosters an awareness of world cultures and the interrelation between political stability and environmental change. The project also will encourage international collaboration betwe ....Agriculture and the Late Bronze Age collapse of the Hittite Empire. National benefit will be accrued through the major scholarly contribution the project makes to a key debate in world archaeology, namely the extent to which environmental change affected ancient complex societies, especially climate change. As such it fosters an awareness of world cultures and the interrelation between political stability and environmental change. The project also will encourage international collaboration between Australian, Turkish and Japanese scholars and will provide training for several research scholars in an area of archaeology in which Australia has a recognised major deficit, namely archaeobotany.Read moreRead less
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
Precisely Dating the Evolution of Complex Societies in Polynesia: The Hawaiian Example. It is of enormous national benefit to develop intellectual innovations that set Australia apart from its neighbours and establish its position as a regional leader in science. Because the Australasian region relies heavily on primary resource exploitation, intellectual developments are crucial for sustainable economic growth. Understanding how societies meet the challenges of resource depletion, landscape de ....Precisely Dating the Evolution of Complex Societies in Polynesia: The Hawaiian Example. It is of enormous national benefit to develop intellectual innovations that set Australia apart from its neighbours and establish its position as a regional leader in science. Because the Australasian region relies heavily on primary resource exploitation, intellectual developments are crucial for sustainable economic growth. Understanding how societies meet the challenges of resource depletion, landscape degradation, drought and population increase can be monitored with archaeological data over hundreds of years. Our research seeks to use an innovative technique for precisely dating major changes in Oceanic societies over the past 500 years, which will provide insights into how modern communities can cope with these problems today. Read moreRead less
PrtFII, A Streptococcus Pyogenes Fibronectin Binding Protein, And Invasive Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$296,540.00
Summary
Our recent work revealed that, in the Aboriginal population, young age is a risk factor for severe invasive diseases caused by group A streptococcus. For group A streptococcus infection to occur, bacterial attachment is the first step. The bacterium attaches to host cells through interactions involving host fibronectin and the pathogen's fibronectin-binding proteins. We have found that streptococcal strains from severe disease cases are more likely to have the gene for PrtFII, a fibronectin bind ....Our recent work revealed that, in the Aboriginal population, young age is a risk factor for severe invasive diseases caused by group A streptococcus. For group A streptococcus infection to occur, bacterial attachment is the first step. The bacterium attaches to host cells through interactions involving host fibronectin and the pathogen's fibronectin-binding proteins. We have found that streptococcal strains from severe disease cases are more likely to have the gene for PrtFII, a fibronectin binding protein, than those from uncomplicated skin sores. In this application we propose to extend this observation and compare biochemical properties of PrtFII from strains belonging to the above two sets of collections. We hypothesise that PrtFII from invasive strains bind to fibronectin more tightly than the proteins from strains that cause uncomplicated infection. We also will test whether sera from invasive disease cases have lower titre of antibodies to the conserved region of PrtFII than sera from uncomplicated cases. A streptococcal vaccine by necessity has to be a multi-component vaccine to cover a wide spectrum of diseases and epidemiological differences. The study proposed here may provide a basis to argue whether or not to include PrtFII in such a multi-component vaccine.Read moreRead less
Intelligent pattern recognition of water end uses enabling recommendations. This project aims to develop a hybrid machine learning method for autonomously disaggregating high- and low-resolution water flow data received from smart meters into discrete end-use events, and a customised recommender system for efficient resource demand management. Project novelty and significance relates to this coupling and autonomous disaggregation of datasets from advanced sensors, enabling more efficient utility ....Intelligent pattern recognition of water end uses enabling recommendations. This project aims to develop a hybrid machine learning method for autonomously disaggregating high- and low-resolution water flow data received from smart meters into discrete end-use events, and a customised recommender system for efficient resource demand management. Project novelty and significance relates to this coupling and autonomous disaggregation of datasets from advanced sensors, enabling more efficient utility services delivery and lower customer utility bills. Project benefits include enabling utilities to better manage and plan resources in the information age, while empowering customers with real-time water end-use data and behaviour changing consumption recommendations.Read moreRead less
Rhinovirus impairs physiological and immunological lung development and causes exacerbation of allergic airways disease. Rhinovirus (RV) infections account for around 90 per cent of asthma exacerbations, yet the mechanisms behind this are unknown. This project will use mouse models to study the effects of early life RV infection and allergic sensitisation on respiratory and immunological development, with the expectation that early life RV infection disrupts anitgen presenting cell function.
Functional magnetic resonance imaging: Decoding the palimpsest. This project aims to model the dynamics of functional magnetic resonance imaging (fMRI) to image new physiology and attain higher resolution. This will enable new aspects of brain dynamics to be imaged, achieving higher resolution and improving interpretation. This project is expected to improve the use and power of fMRI, unlock new avenues for probing brain function and save experimental costs. This will have many uses in neuroscie ....Functional magnetic resonance imaging: Decoding the palimpsest. This project aims to model the dynamics of functional magnetic resonance imaging (fMRI) to image new physiology and attain higher resolution. This will enable new aspects of brain dynamics to be imaged, achieving higher resolution and improving interpretation. This project is expected to improve the use and power of fMRI, unlock new avenues for probing brain function and save experimental costs. This will have many uses in neuroscience, brain imaging technology and fMRI analysis software.Read moreRead less