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.
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
The Chief Investigators have worked as a team for 20 years as part of a successful NHMRC Program Grant that was renewed on three successive occasions and subsequently under a NHMRC Block Grant to QIMR. Their combined expertise covers the whole spectrum from the bedside to the bench with respect to clinical studies and fundamental molecular studies of iron homeostasis. The common theme of iron homeostasis and iron overload pervades virtually all the research of the team. The team�s research has l ....The Chief Investigators have worked as a team for 20 years as part of a successful NHMRC Program Grant that was renewed on three successive occasions and subsequently under a NHMRC Block Grant to QIMR. Their combined expertise covers the whole spectrum from the bedside to the bench with respect to clinical studies and fundamental molecular studies of iron homeostasis. The common theme of iron homeostasis and iron overload pervades virtually all the research of the team. The team�s research has led to fundamental observations of iron regulation and homeostasis and the development of guidelines for the management of, and screening for, haemochromatosis, recognized as the most common inherited disorder of Caucasian populations. The proposed research encompasses molecular studies aimed at deciphering the mechanisms of iron absorption and transport; how these processes are regulated; and clinical studies on patients diagnosed with haemochromatosis. The findings are particularly pertinent to the diagnosis, management and prevention of clinical haemochromatosis.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE160100218
Funder
Australian Research Council
Funding Amount
$840,000.00
Summary
A Nuclear Magnetic Resonance Facility for Modern Molecular Analysis. A nuclear magnetic resonance facility for modern molecular analysis:
This project aims to network a new 500 MHz nuclear magnetic resonance (NMR) spectrometer and new consoles for existing instruments with an automated sample changer for a 600 MHz NMR spectrometer. This designed to increase the capacity of Queensland-based researchers to undertake state-of-the-art studies in chemistry, drug design, and materials science. The ne ....A Nuclear Magnetic Resonance Facility for Modern Molecular Analysis. A nuclear magnetic resonance facility for modern molecular analysis:
This project aims to network a new 500 MHz nuclear magnetic resonance (NMR) spectrometer and new consoles for existing instruments with an automated sample changer for a 600 MHz NMR spectrometer. This designed to increase the capacity of Queensland-based researchers to undertake state-of-the-art studies in chemistry, drug design, and materials science. The new knowledge from these studies may lead to the development of new drugs, new crop protection agents and new photovoltaic materials. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120103152
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Development of next generation drugs against Helicobacter pylori. Gastric cancer is the second leading cause of cancer-related death in the world and infection by Helicobacter pylori bacteria is the main cause of this disease. The aim of this project is to develop new approaches to treat Helicobacter pylori infection that will give superior results and lower side effects than available therapies.
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.
Sulfoxide Polymers - A New Paradigm in Polymer Design. Low fouling polymers are important for moderating interactions of molecules and particles with cells. In pharmaceutical sciences they are essential tools for extending the pharmacokinetics of dissolved drugs. However, the widely-used low-fouling polymer, poly(ethylene glycol) (PEG) has been recently reported to induce formation of anti-PEG antibodies. Polymeric alternatives to PEG are thus desperately needed. We introduce in this project sup ....Sulfoxide Polymers - A New Paradigm in Polymer Design. Low fouling polymers are important for moderating interactions of molecules and particles with cells. In pharmaceutical sciences they are essential tools for extending the pharmacokinetics of dissolved drugs. However, the widely-used low-fouling polymer, poly(ethylene glycol) (PEG) has been recently reported to induce formation of anti-PEG antibodies. Polymeric alternatives to PEG are thus desperately needed. We introduce in this project super-hydrophilic polymers incorporating sulfoxide groups, mimics of the polar solvent DMSO. The project aims to explore how polymer architecture can enhance biocompatibility and reduce biofouling. The outcome will be a new class of low-fouling polymeric materials with broad application in the biosciences.Read moreRead less