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.
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.
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.
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.
Signaling Pathways To Enhance Potency Of AMPK-targeting Drugs
Funder
National Health and Medical Research Council
Funding Amount
$661,966.00
Summary
Sedentary lifestyles and consumption of high energy foods has led to epidemics of obesity-related metabolic diseases that place enormous financial and medical burden on the Australian economy. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK) which functions as both a cellular fuel gauge and co-ordinator of whole-body metabolism. Our goal is to improve AMPK drug potency by identifying novel processes that sensitize AMPK to drugs.
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
Novel vitamin E analogues disrupt autocrine signalling and angiogenesis: Mechanistic studies and relevance to cancer management. Breast and mesothelioma cancers present a severe problem in Australia and many patients succumb due to lack of appropriate treatment. We believe that vitamin E analogues, selective drugs efficient against cancer cells, hold a promise as future drugs against these two pathologies. Vitamin E analogues act by several mechanisms, including toxic effect on the cancer cells ....Novel vitamin E analogues disrupt autocrine signalling and angiogenesis: Mechanistic studies and relevance to cancer management. Breast and mesothelioma cancers present a severe problem in Australia and many patients succumb due to lack of appropriate treatment. We believe that vitamin E analogues, selective drugs efficient against cancer cells, hold a promise as future drugs against these two pathologies. Vitamin E analogues act by several mechanisms, including toxic effect on the cancer cells and also on cells that are necessary for efficient progression of tumours, such as cells of the malignant blood vessels. Results of this project will be used to prepare clinical testing of these highly promising drugs.Read moreRead less
Developing efficient cancer therapies by targeting of vitamin E analogues to mitochondria. We propose a new strategy of developing efficient anti-cancer agents. Results of this project will lead to establishing highly proising anti-cancer drugs and will open new approaches for the design of novel agents that efficiently kill cancer cells.
Predicting the movement speeds of animals. The project seeks to reveal how marsupials modify their movement patterns and speeds as they navigate risky environments, and show how movement contributes to vulnerability and resilience. Movement is central to animal behaviour and the survival of species, because it underlies feeding, mating and the ability to escape from predators. However, we lack a framework for predicting how fast animals should move through their habitats given their needs to con ....Predicting the movement speeds of animals. The project seeks to reveal how marsupials modify their movement patterns and speeds as they navigate risky environments, and show how movement contributes to vulnerability and resilience. Movement is central to animal behaviour and the survival of species, because it underlies feeding, mating and the ability to escape from predators. However, we lack a framework for predicting how fast animals should move through their habitats given their needs to conserve energy, avoid detection by predators and minimise risks of injury or death. This project aims to develop mathematical models to predict how fast animals should move and then test these predictions using native species of conservation concern. This is expected to extend the field of performance ecology as well as inform management strategies for vulnerable marsupials.Read moreRead less