I am a cellular immunologist interested in the study of cytokines and other regulatory molecules in inflammatory and immune responses. One key area relates to the effect on sunlight on cell-mediated immunity.
Maintenance Of Regulatory T Cells During Inflammation And Tumor Development By IL-33
Funder
National Health and Medical Research Council
Funding Amount
$676,979.00
Summary
Regulatory T cells (Tregs) are required for preventing inflammation in tissues such as lung, fat and skin. We found recently, that the signalling molecule IL-33 is required for tissue Tregs and up-regulated during inflammation and tumor development. We therefore aim to determine the role of IL-33 in maintenance and function of Tregs and to identify molecular targets of IL-33 that may allow therapeutic targeting of Tregs in patients with inflammatory conditions or cancer.
Our research has identified unprecedented communications between the microbes that colonize our body’s surfaces and killer T cell immunity. Our findings indicate that microflora is key to a healthy balance between two immune mediator systems that have opposing effect on T cell immunity. The project will extend our understanding of how this regulated and seeks to harness these novel insights to explain the well known, but poorly understood role of microbes in autoimmune diseases.
The Role Of IL21 In Integrating Proliferation, Migration And Differentiation Following B Cell Activation.
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Immunity is essential to health and requires the production of antibodies. The best antibodies are made by B-cells coming from specialised structures, called germinal centres (GC). To understand why sometimes immunity is excellent - childhood vaccines - and other times not - HIV infection, aged people - we need to understand what happens inside GC. Our prediction is that by understanding GC B cell behaviour, we will resolve good from poor immune responses and thereby develop improvements.
NK Cell Subsets And Their Role In Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$173,522.00
Summary
Natural killer (NK) cells are 5-10% of white blood cells of the immune system that represent one of our first lines of defense against microbes and cancer development. Recent evidence strongly suggests that NK cells are major cells of importance in the immune system, not only in acting as killers of cancer cells or virus-infected cells, but also in regulating the adaptive memory components of the immune response. Despite our greater knowledge of NK cell biology, we still know very little about t ....Natural killer (NK) cells are 5-10% of white blood cells of the immune system that represent one of our first lines of defense against microbes and cancer development. Recent evidence strongly suggests that NK cells are major cells of importance in the immune system, not only in acting as killers of cancer cells or virus-infected cells, but also in regulating the adaptive memory components of the immune response. Despite our greater knowledge of NK cell biology, we still know very little about the diversity that exists within the NK cell population. The development and maturation of NK cells requires far greater study and this proposal aims to examine this question in the best experimental model, the mouse. We have recently made an important breakthrough concerning the distinct functional behavior of newly discovered NK cell subsets. We now aim to develop a more integrated model of NK cell development, such that vaccines and adjuvants designed to prevent and ameliorate lethal and chronic infectious diseases and cancer can be more rationally designed.Read moreRead less
Immunotherapy is emerging as one of the largest breakthroughs in cancer therapy in the last 30 years, due to the recent approval of the antibody therapeutics Ipilimumab (anti-CTLA4) and Pembrolizumab (anti-PD-1). This has greatly increased interest in other immune activating modalities, either for monotherapy, or in combination with antibody therapy. Here we propose to decipher molecular mechanisms that underpin the biological function of a new class of immune activating drugs (IL-2 superkines).
Follicular Cytotoxic T Cell Differentiation And Function In Infection And B-cell Lymphoma
Funder
National Health and Medical Research Council
Funding Amount
$963,892.00
Summary
Cytotoxic T cells eliminate infected or cancerous cells, constituting a major arm of the immune defence. In this study, we will investigate a subset of cytotoxic T cells that particularly migrate into B cell follicles to control infection and malignancy. Understanding of the differentiation and function of this subset, termed as follicular cytotoxic T (TFC) cells, will help us to develop new strategies to treat EBV and HIV infections as well as B cell lymphomas.
Investigating B Cell Development, Maintenance And High-affinity Antibody Production By ENU Mutagenesis
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
B cells are essential for the protection against infections. This application aims to identify new genes that are crucial for the development or function of B cells and will investigate how mutations in newly discovered genes contribute to defects in the development and function of B cells and the pathogenesis of B cell leukaemia.
Determining The Role Of Rel/NF-kB Transcription Factors In CD8 T Cell Homeostasis.
Funder
National Health and Medical Research Council
Funding Amount
$426,500.00
Summary
NF-kB proteins comprise a family of transcription factors that regulate key genes involved in immune responses, inflammation, cell death and proliferation. This family of proteins are potential drug targets for treatment of various diseases. How and when such inhibitors are used in clinical situations depends on understanding how and which cells of the immune system are specifically affected by the absence of NF-kB proteins. In a number of treatment settings intercurrent viral infections occur f ....NF-kB proteins comprise a family of transcription factors that regulate key genes involved in immune responses, inflammation, cell death and proliferation. This family of proteins are potential drug targets for treatment of various diseases. How and when such inhibitors are used in clinical situations depends on understanding how and which cells of the immune system are specifically affected by the absence of NF-kB proteins. In a number of treatment settings intercurrent viral infections occur frequently and therefore there is an even greater need to understand how the immune system may be affected or compromised in response to the primary treatment. This work will provide insights into the cellular and molecular mechanisms affected by the absnece of a particular NF-kB family member (NF-kB1) in CD8 T cells during normal T cell homeostasis and when challenged with viruses. What we learn from our experiments could have important implications for the development of vaccines.Read moreRead less