Regulation Of Toxoplasma By The NLRP1 Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$623,070.00
Summary
Toxoplasmosa is an endemic pathogen worldwide, approaching 80% of the population in some areas, with a large burden of disease, particularly of immunocompromised and pregnant individuals. Our preliminary data identifies a receptor protein in immune cells that detects Toxoplasma. This can defeat the parasite, but also causes pathology for the host. The outcome of our project will work out what part of Toxoplasma is recognized by this receptor, with significance for the treatment of Toxoplasmosis.
Sterile inflammation as a determinant of adaptive immunity. When we injure ourselves, the site of injury becomes inflamed, which may help healing or cause trouble. This project aims to understand how the normal response to injury is controlled and why the process may sometimes go wrong.
Innate Immune Factors Regulate Steroid-resistant Airways Hyperreactivity And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$524,456.00
Summary
Infection induced asthma is often difficult to manage because of lack of efficacy of steroid treatment. The innate immune system plays an important role in inflammation associated with infection. I have shown that two innate immune factors, IFN-gamma and lipopolysaccharide (LPS), induce airways hyperreactivity that is resistant to steroid therapy in a mouse model. Identification of how this pathway works may help in the treatment of infection induced steroid-resistant difficult to manage asthma.
Molecular Regulation Of Blood Cell Production And Function
Funder
National Health and Medical Research Council
Funding Amount
$18,333,174.00
Summary
The blood-forming system is an intricately controlled balance of cell proliferation, maturation and functional activity that is essential for oxygen transport throughout the body, blood clotting, and effective immune responses. Defining the genes and molecules that orchestrate blood cell production and function is crucial, not only for understanding the role of blood in health, but for establishing the bases of blood cell disorders such as autoimmunity and leukaemia, and for devising new clinica ....The blood-forming system is an intricately controlled balance of cell proliferation, maturation and functional activity that is essential for oxygen transport throughout the body, blood clotting, and effective immune responses. Defining the genes and molecules that orchestrate blood cell production and function is crucial, not only for understanding the role of blood in health, but for establishing the bases of blood cell disorders such as autoimmunity and leukaemia, and for devising new clinical strategies for fighting these lethal diseases. This program is conducted by a large, established team of investigators that have made world-class contributions to understanding blood cell formation and function for more than 30 years. Their work established the modern era of molecular haematology via discovery and analysis of blood cell hormones (colony-stimulating factors or CSFs), their receptors and intracellular mediators, which resulted in development of treatments for millions of cancer patients. The program is a multidisciplinary, team approach to fundamental biological questions with a focus on potential clinical and commercial outcomes involving collaborations with clinical medicine and the pharmaceutical industry. Research will focus on meshing novel genetic approaches in mice with translation studies in humans to identify new validated targets for therapeutic intervention in blood cell diseases, as well as building on the team s expertise in cytokine action with emphasis on the actions of the suppressor of cytokine signalling (SOCS) molecules, a key family of proteins that controls cytokine actions.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180101075
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Novel immune cell subsets in the centre nervous system and supporting tissues. This project aims to identify and characterise novel resident immune cell subsets within the brain and retina, and their close supporting tissues. The project expects to generate new knowledge in the areas of neuroimmunology and ocular immunology by using molecular and cellular techniques to examine the diversity of immune cells within the brain and retina. It is expected that the project will advance our understandin ....Novel immune cell subsets in the centre nervous system and supporting tissues. This project aims to identify and characterise novel resident immune cell subsets within the brain and retina, and their close supporting tissues. The project expects to generate new knowledge in the areas of neuroimmunology and ocular immunology by using molecular and cellular techniques to examine the diversity of immune cells within the brain and retina. It is expected that the project will advance our understanding of the biological mechanisms that protect the central nervous system from harmful inflammation and thus improve our knowledge of the immunobiology of the brain and eye.Read moreRead less
Molecular Mechanisms of NOD signalling. Alterations in NOD1 and NOD2 (nucleotide-binding oligomerization domain containing 1 and 2) signalling have been implicated in various human inflammatory diseases. Therefore, a clear understanding of the molecular signalling pathways is important to gain further insights into potential drug targets for the treatment of these diseases. Using novel experimental approaches, this project aims to identify new members of the NOD signalling pathway. It will test ....Molecular Mechanisms of NOD signalling. Alterations in NOD1 and NOD2 (nucleotide-binding oligomerization domain containing 1 and 2) signalling have been implicated in various human inflammatory diseases. Therefore, a clear understanding of the molecular signalling pathways is important to gain further insights into potential drug targets for the treatment of these diseases. Using novel experimental approaches, this project aims to identify new members of the NOD signalling pathway. It will test the effect of pharmacological inhibition of established molecules such as RIPK2 or IAPs in NOD dependent models for human diseases. Outcomes of this study will be of the utmost interest for the treatment of NOD driven diseases such as Crohn's disease, Blau syndrome or asthma.Read moreRead less
Analysing the protective role of platelets during malaria infection. Platelets protect the host during malarial infection. This project aims to study how platelets kill the malaria parasite by investigating the role of host molecules and their potential as novel antimalarial agents. The role of platelets in the pathogenesis of cerebral malaria syndrome will also be investigated.
SNARE-mediated perforin and cytokine release in natural killer cells. Cytotoxic cells release toxic granules and cytokine messengers to kill pathogen infected and cancerous cells and to mount immune responses. This project will investigate different SNARE molecules that regulate the secretion of perforin from granules and cytokines from other carriers, assisting in the understanding of complex but essential cellular pathways.
Discovery Early Career Researcher Award - Grant ID: DE120101340
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Subversion of innate immune responses by pathogenic Escherichia coli. This project will determine how bacteria that cause diarrhoeal diseases prevent the immune system from signalling efficiently. It will provide important information not only about how the bacteria establish disease, but also provide insight into the host response in the early stages of infection.
Deciphering novel cross-talk between innate cytokine receptors. Understanding the basic functions of interferons, how they signal to cells, is central to understanding fundamental immunity. Interferons are crucial molecules of the immune system that are important for normal cell development and they protect the body from viral infection and cancer but can be deleterious in different autoimmune diseases and trauma settings. Preliminary Data shows there is a pathway of interferon signalling that h ....Deciphering novel cross-talk between innate cytokine receptors. Understanding the basic functions of interferons, how they signal to cells, is central to understanding fundamental immunity. Interferons are crucial molecules of the immune system that are important for normal cell development and they protect the body from viral infection and cancer but can be deleterious in different autoimmune diseases and trauma settings. Preliminary Data shows there is a pathway of interferon signalling that has previously been overlooked. This project aims to understand how this pathway works and how it contributes to the normal workings of cells. This fundamental science has future consequences for the design of vaccines and for the design of therapeutics to treat diseases that show defective interferon signalling.Read moreRead less