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.
Functional Nano-cement Scaffolds For The Treatment Of Osteoporotic Bone Defects
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
Osteoporosis affects 1.2 million Australians and will cost $33.6 billion by 2022. This study aims to develop a novel nano-cement platform for custom-designed bone repair in osteoporosis, by using purpose-designed nanomaterials and advanced 3D printing technique. The research findings will lead to the development of a new bone repair strategy, expand knowledge on both biomaterials engineering and osteoporosis treatment, and improve the quality of life of Australians.
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.
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.
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
Creating a non-invasive window into the mind. This project aims to create better tools to study the human mind. This project expects to generate new knowledge that can be used to non-invasively image neuronal activity. Expected outcomes include the development of unique new Magnetic Resonance Imaging (MRI) instruments to study neuronal activity in both highly controlled laboratory conditions and in humans, with the spatial and temporal resolution needed to study the neuronal circuitry that drive ....Creating a non-invasive window into the mind. This project aims to create better tools to study the human mind. This project expects to generate new knowledge that can be used to non-invasively image neuronal activity. Expected outcomes include the development of unique new Magnetic Resonance Imaging (MRI) instruments to study neuronal activity in both highly controlled laboratory conditions and in humans, with the spatial and temporal resolution needed to study the neuronal circuitry that drives low and high-level brain functions, i.e., creating a window into the mind. In the future, outcomes from this study could improve our understanding of mental disorders, advance computer brain interface technology, and inspire the next paradigm shift in artificial intelligence.Read moreRead less
Functional Contribution Of Fetal Microchimeric Cells In Transgenic Models Of Maternal Tissue Repair In And After Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$542,462.00
Summary
Fetal stem cells cross into the mother during pregnancy and persist lifelong in her tissues. To determine whether helpful or harmful, we will study how these cells contribute to healing both after acute injury and in chronic genetic models like brittle-bone disease and muscular dystrophy. This research will inform long-term consequences of pregnancy, important for women's health and longevity, and help develop a promising form of stem cell therapy.
A Biologically Responsive and Anatomically Authentic Human Nasal Model. As respiratory conditions caused by pollutants and viruses become more prevalent, human nasal models to study infection/protection mechanisms and nasal drug/vaccine delivery are increasingly important. This project aims to develop a world-first human nasal model to mimic both anatomical and biological aspects of the nasal cavity and predict the distribution and deposition of fine particles and the resultant biological respon ....A Biologically Responsive and Anatomically Authentic Human Nasal Model. As respiratory conditions caused by pollutants and viruses become more prevalent, human nasal models to study infection/protection mechanisms and nasal drug/vaccine delivery are increasingly important. This project aims to develop a world-first human nasal model to mimic both anatomical and biological aspects of the nasal cavity and predict the distribution and deposition of fine particles and the resultant biological response from the nasal mucosa. The aim is to overcome a key fabrication challenge - to 3D print an anatomically accurate nasal construct with a porous wall on which to grow and mature functional nasal tissue that lines a nasal cavity wall. The benefit would be enabling faster development of more targeted drugs and vaccines.Read moreRead less
A Micro-Physiological System to Mimic Human Microbiome-Organ Interactions. This project aims to mimic gut microbiome-organ interactions by developing a microbial-gut coculture chip, which can reversibly interface with other organs-on-chips. This is achieved through the systematic integration of highly customisable biofabrication and microfluidic technologies. This project fills a critical technological gap in the availability of an animal-alternative system to investigate microbiome-host interac ....A Micro-Physiological System to Mimic Human Microbiome-Organ Interactions. This project aims to mimic gut microbiome-organ interactions by developing a microbial-gut coculture chip, which can reversibly interface with other organs-on-chips. This is achieved through the systematic integration of highly customisable biofabrication and microfluidic technologies. This project fills a critical technological gap in the availability of an animal-alternative system to investigate microbiome-host interactions, which will greatly complement existing meta-omics approaches. The deliverables include a proof-of-concept system validated for gut-liver axis as well as the creation of new knowledge and framework to assimilate design thinking and advanced manufacturing to elevate tissue engineering into physiology engineering. Read moreRead less