There are two arms to the immune system, one that learns and adapts, which can cause autoimmune disease, and another that is immediate and innate, and can cause autoinflammatory disease. This proposal continues our work in the characterization of rare genetic autoinflammatory disesaes and extrapolates these studies to more common chronic inflammatory diseases. This stands to improve current diagnosis and treatment, and elucidate future drug targets that could be targeted clinically.
The Role Of Perivascular Macrophages In The Regulation Of Skin Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$616,518.00
Summary
Neutrophils are key defenders against bacterial infections. In this application we will test the hypothesis that perivascular macrophages play a critical role in the recruitment of neutrophils to site of cutaneous infection, and that these cells are targeted and destroyed by bacterial virulence factors. Our studies will gain novel insight into the leukocyte homing paradigm and shed new light on the mechanisms of microbial immuno-evasion.
Elucidating the roles of steroid receptors in mitochondria. This project aims to elucidate the roles of newly discovered steroid receptors in the functions of mitochondria. The project will characterise their impact on cellular respiration, oxidative stress, and the induction of inflammation. By defining these processes in the healthy state and in response to common environmental challenges of infection and smoke exposure, the project will characterise the fundamental biology of entirely new pro ....Elucidating the roles of steroid receptors in mitochondria. This project aims to elucidate the roles of newly discovered steroid receptors in the functions of mitochondria. The project will characterise their impact on cellular respiration, oxidative stress, and the induction of inflammation. By defining these processes in the healthy state and in response to common environmental challenges of infection and smoke exposure, the project will characterise the fundamental biology of entirely new processes of how normal body hormones and administered steroids may function. This may eventually lead to new and more effective ways to control inflammation that will have significant benefits to mammalian health and improve health care and agriculture outcomes.Read moreRead less
Manipulating The Fine-turning Of The Innate Immune Response In Disease
Funder
National Health and Medical Research Council
Funding Amount
$938,910.00
Summary
I am an international expert on the body’s first-line defense system, the innate immune response. My Fellowship focuses on studying and manipulating innate immune molecules called interferons. My research will lead to improved management of female reproductive disease, autoimmune disorders, infections and cancer through new diagnostics and therapies targeting the interferon system. The basic knowledge I generate on regulating the immune response will be applicable to a range of medical fields.
An investigation into CD1a, a versatile antigen-presenting molecule. This project aims to investigate how T lymphocytes are activated by lipids presented by the skin-associated antigen-presenting molecule, CD1a. Using X-ray crystallography and cellular immunology, we will provide fundamental insight into this poorly understood immunological axis. We will determine the molecular basis for how CD1a presents diverse self and foreign lipids, and how such CD1a-lipid complexes are recognised by the r ....An investigation into CD1a, a versatile antigen-presenting molecule. This project aims to investigate how T lymphocytes are activated by lipids presented by the skin-associated antigen-presenting molecule, CD1a. Using X-ray crystallography and cellular immunology, we will provide fundamental insight into this poorly understood immunological axis. We will determine the molecular basis for how CD1a presents diverse self and foreign lipids, and how such CD1a-lipid complexes are recognised by the responding T cells. This basic science discovery project will provide substantial new knowledge in the burgeoning field of lipid-mediated immunity, which should ultimately lead to new therapies targeting the CD1a lipid display molecule to either prevent immune mediated damage or promote protective immunity as required.Read moreRead less
Immune-imprinting nanoparticles (iNPs). This research promises new classes of immune-imprinting, biodegradable nanoparticles (iNPs) with anti-inflammatory properties. The engineering of such particles requires fundamental understanding of their properties that enable specific cellular interactions to regulate immunity with new anti-inflammatory pathways. For pulmonary delivery, spray-dried amino acid microspheres with tailored surfaces as carriers can be generated using the innovative microfluid ....Immune-imprinting nanoparticles (iNPs). This research promises new classes of immune-imprinting, biodegradable nanoparticles (iNPs) with anti-inflammatory properties. The engineering of such particles requires fundamental understanding of their properties that enable specific cellular interactions to regulate immunity with new anti-inflammatory pathways. For pulmonary delivery, spray-dried amino acid microspheres with tailored surfaces as carriers can be generated using the innovative microfluidic drying approach. The potential applications of iNPs are wide-ranging and are not restricted to pulmonary targeting. The potential commercial implications for Australia's emerging biopharmaceutical industry are substantial.Read moreRead less
Investigating the actions of anti-inflammatory pathways in chronic lung disease. There is an urgent need to develop better drugs for Chronic Obstructive Pulmonary Disease (COPD) as patients become resistant to currently used anti-inflammatory drugs with disease progression. This research will uncover fundamental biology into an important class of anti-inflammatory receptor termed ALX/FPR2. This receptor normally coordinates the clearance of infection and injured tissue and subsequently switches ....Investigating the actions of anti-inflammatory pathways in chronic lung disease. There is an urgent need to develop better drugs for Chronic Obstructive Pulmonary Disease (COPD) as patients become resistant to currently used anti-inflammatory drugs with disease progression. This research will uncover fundamental biology into an important class of anti-inflammatory receptor termed ALX/FPR2. This receptor normally coordinates the clearance of infection and injured tissue and subsequently switches off inflammation. Essential knowledge into why this receptor pathway fails to switch off inflammation will be determined. Furthermore, the development of targeting strategies to this receptor represents an innovative approach to blocking damaging and chronic airway inflammation.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220100823
Funder
Australian Research Council
Funding Amount
$442,482.00
Summary
Elucidating ATPase function during NLRP3 inflammasome assembly. Humans and animals are constantly exposed to microbes, which inhabit their external environment as well as body surfaces such as the skin and gut. We are, however, able to co-exist with these microbes, because our immune system protects us from these everyday encounters. This proposal will reveal how an important immune protein called NLRP3 senses microbes and other physiological processes. When NLRP3 senses such factors and is acti ....Elucidating ATPase function during NLRP3 inflammasome assembly. Humans and animals are constantly exposed to microbes, which inhabit their external environment as well as body surfaces such as the skin and gut. We are, however, able to co-exist with these microbes, because our immune system protects us from these everyday encounters. This proposal will reveal how an important immune protein called NLRP3 senses microbes and other physiological processes. When NLRP3 senses such factors and is activated, it induces the release of messenger substances to alert other immune cells. This research will deliver fundamental knowledge of how animals normally co-exist with microbes.Read moreRead less
During injury or infection, our body’s immune system protects us by launching inflammation. But uncontrolled inflammation drives common diseases such as cancer, diabetes and Alzheimer’s. This project will reveal how the body produces interleukin-1? – a protein at the heart of inflammation and disease – so we can design better strategies for treating patients with inflammation-driven disease.
All cells in the body need to get their energy from somewhere, and the chemical basis of their energy supply varies depends on many factors, including their location and rate of cell division. We have found that an important population of white blood cells that control the character and magnitude of most immune responses appear to use an unusual source of their energy. If true this would provide a range of new opportunities to control the numbers and activities of these cells, a thereby control ....All cells in the body need to get their energy from somewhere, and the chemical basis of their energy supply varies depends on many factors, including their location and rate of cell division. We have found that an important population of white blood cells that control the character and magnitude of most immune responses appear to use an unusual source of their energy. If true this would provide a range of new opportunities to control the numbers and activities of these cells, a thereby control the character and magnitude of immune responses.Read moreRead less