The Interferon System In Innate Immune Responses To Disease
Funder
National Health and Medical Research Council
Funding Amount
$836,818.00
Summary
My research investigates special proteins called cytokines in the body’s first-line defence against infection, inflammation and cancer. I will characterise how cells respond, the signals that mediate effects, using sophisticated genetic and new computational techniques to manage and analyse data. One focus is a new cytokine we discovered that protects against infections of the reproductive tract –a global health and socio-economic problem affecting 1 billion people.
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.
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.
A Novel Class Of Negative Regulators Of Interleukin-6 Signalling
Funder
National Health and Medical Research Council
Funding Amount
$626,950.00
Summary
Cytokines are protein messengers that activate the immune system to fight infections. When they are too active they cause inflammation and autoimmune diseases so their activity needs to be tightly controlled. We have discovered a new family of regulators (the MARCH proteins) that inhibit cytokine activity by routing cytokine receptors for destruction. We aim to understand how this process works in detail and the role of MARCH proteins in vivo in ameliorating autoimmune diseases.
Altered Gp130-mediated Signalling In The Regulation Of Pulmonary Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$373,956.00
Summary
Pulmonary fibrosis is a chronic diffuse interstitial lung disease often of unknown cause, characterised pathologically by inflammation and fibrosis of the lung tissue. The prognosis is poor with a 50% mortality at five years after diagnosis and considerable morbidity during those years. Previous investigations have documented the role for inflammation in the development of pulmonary fibrosis and current therapeutic strategies are aimed at suppressing the inflammation using anti- inflammatory dru ....Pulmonary fibrosis is a chronic diffuse interstitial lung disease often of unknown cause, characterised pathologically by inflammation and fibrosis of the lung tissue. The prognosis is poor with a 50% mortality at five years after diagnosis and considerable morbidity during those years. Previous investigations have documented the role for inflammation in the development of pulmonary fibrosis and current therapeutic strategies are aimed at suppressing the inflammation using anti- inflammatory drugs, almost exclusively steroids. The effectiveness of steroids is variable although generally poor and can be associated with significant side effects suggesting that other approaches need to be considered. Data generated over the past decade also have established the concept that the molecular processes underlying the development of fibrosis may represent a new opportunity for therapeutic intervention. This project will build on previous studies examining the effects of a family of molecules called cytokines that signal through gp130 as critical determinants of disease susceptibility and progression. gp 130 is a shared component in the receptor complexes for IL-6 family cytokines and can signal down two major pathways. We have shown that the development of lung fibrosis depends on which specific signalling pathway is used. This study will determine how fibrosis is controlled by these pathways. Our data raises the possibility of developing pharmacological manipulators of gp130 signalling pathways that would suppress fibrosis but leave normal cellular defense mechanisms necessary for host defense in the lung intact.Read moreRead less
Microbial Evasion Of A Novel Inflammasome By Salmonella
Funder
National Health and Medical Research Council
Funding Amount
$486,174.00
Summary
Microbes quickly evolve to evade detection by the innate immune system, the body’s first line of defence against infection. This project investigates the mechanisms by which the immune system recognises bacterial infection, and pathways used by bacteria to avoid these defences. This research will lead to a better understanding of mechanisms underlying resistance and susceptibility to bacterial infection.
Dissecting FLT3 Signalling In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$498,328.00
Summary
Each year approximately 6000 Australian adults and children are diagnosed with leukaemia, lymphoma or a related blood disorder, accounting for about 15% of all cancers. Acute Myeloid Leukaemia (AML) is the most common form of leukaemia in adults resulting from an accumulation of immature myeloid cells in the bone marrow and peripheral blood as a result of sustained, abnormal cell growth and survival together with a block in normal blood cell formation. There is still a major research effort aime ....Each year approximately 6000 Australian adults and children are diagnosed with leukaemia, lymphoma or a related blood disorder, accounting for about 15% of all cancers. Acute Myeloid Leukaemia (AML) is the most common form of leukaemia in adults resulting from an accumulation of immature myeloid cells in the bone marrow and peripheral blood as a result of sustained, abnormal cell growth and survival together with a block in normal blood cell formation. There is still a major research effort aimed at understanding the mechanisms that lead to AML formation and it is clear that multiple AML oncogenes and tumour suppressors remain to be identified. Identification of further events involved in AML is important as it will provide avenues for more specific and less toxic treatments. These are needed because current success rates for AML remain relatively poor. It is critical that research into the understanding of the pathways and events involved in AML keeps pace with the rapid development of new approaches for therapeutic agents. Together this will greatly increase the scope for therapeutic intervention over the next decade. In this application we investigate the role of a new molecular pathway in AML. Our studies have identified a gene of particular interest that we propose normally prevents AML formation and therefore is frequently turned off by the cellular changes that lead to AML. We propose that silencing of this gene is particularly important in those AML cases which have mutations in the cell surface receptor FLT3 (about 30% of AML cases). We will use a number of molecular and cell biology approaches to manipulate this gene in mouse cell lines, normal mouse cells and human AML cells. A better understanding of the role of this gene and the associated pathway involving FLT3 may generate new leads for therapeutic approaches.Read moreRead less
Does CD123 Provide A Biological Advantage To Leukaemia Stem Cells?
Funder
National Health and Medical Research Council
Funding Amount
$647,637.00
Summary
Leukaemia is a devastating form of blood cancer affecting both young and old. We need to understand the diseased stem cell to eradicate this disease. Current therapy is poorly tolerated and the majority of patients ultimately die at relapse. We intend to investigate how we can make the cells more susceptible to therapy by understanding their biology.