I am an Immunologist interested in the role of B-lymphocytes, their survival and expression of a novel chemoreceptor in Autoimmunity. I also study the important role of Neuropeptide Y in modulating key immune functions.
The establishment of an immune system that is able to distinguish between self and non-self is of fundamental importance for good health and survival. How this specificity is achieved has been an area of intense investigation for many years because a breakdown of this process leads to the development of autoimmune diseases, such as diabetes, or an inability to fight pathogenic organisms. It has been known for many years that the development T cells, a subset of cells involved in mounting immune ....The establishment of an immune system that is able to distinguish between self and non-self is of fundamental importance for good health and survival. How this specificity is achieved has been an area of intense investigation for many years because a breakdown of this process leads to the development of autoimmune diseases, such as diabetes, or an inability to fight pathogenic organisms. It has been known for many years that the development T cells, a subset of cells involved in mounting immune responses, occurs in the thymus. The thymus produces large numbers of immature T cells (called thymocytes) from which a small number receive the appropriate signals to survive and develop into mature T cells. These tailor-made T cells can then enter the blood and peripheral lymphoid organs where they fight infectious organisms without reacting against host (i.e. self) tissues. The work for this project is aimed at determining how proteins inside thymocytes transmit signals that determine whether thymocytes either survive, and develop into T cells, or are eliminated because they react too strongly with self proteins. We have established that a protein called c-Cbl is central to this process as it regulates the initial strength of the signal that determines the fate of thymocytes. Our aim is to identify the putative key protein regulated by c-Cbl that can sense when a signal is too strong following the binding of a thymocyte to a self protein and directs a cell death signalling response. From this critical point of signal splitting we also aim to identify proteins that relay the death signal to the nucleus where they trigger the production of well-characterised proteins required to mediate cell death. By identifying the proteins in this signalling pathway we will have a greater capacity to control the magnitude of immune responses and therefore be able to lessen tissue damage caused by autoimmune reactions.Read moreRead less
The Function Of Histidine-rich Glycoprotein In Inflammation And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$455,670.00
Summary
This research proposal investiagtes the role of a molecule known as histidine-rich glycoprotein (HRG) in the important diseases of cancer and inflammation. Inflammatory diseases can occur when the the normal checks on the immune system breakdown resulting in attacks on the body leading to tissue damage (e.g rheumatoid arthritis) and are significant contributors to morbidity and health costs in Australia. Cancer is the leading cause of death in Australia (28.4% of deaths in 2003). HRG has been im ....This research proposal investiagtes the role of a molecule known as histidine-rich glycoprotein (HRG) in the important diseases of cancer and inflammation. Inflammatory diseases can occur when the the normal checks on the immune system breakdown resulting in attacks on the body leading to tissue damage (e.g rheumatoid arthritis) and are significant contributors to morbidity and health costs in Australia. Cancer is the leading cause of death in Australia (28.4% of deaths in 2003). HRG has been implicated in controlling important aspects of inflammatory and cancer disease progression. Namely, HRG appears to regulate the formation and clearance of substances known as immune complexes - the primary cause of tissue damage in this disease. Furthermore, HRG may also control the process of cell invasion which is crucial for the migration of white blood cells of the immune system (leukocytes) to sites of inflammation to combat infections, and is also an important mechanism by which malignant tumour cells escape from primary tumour sites and spread throughout the circulation to other sites in the body. It is this process that makes cancer such a deadly disease. This study aims to define how HRG contributes to these important processes. This information may allow the development of new therapeutic approaches for the treatment of inflammatory diseases and cancer.Read moreRead less
Identification of novel markers of inflammation. This project will benefit Australia as it will increase basic understanding of inflammatory processes, result in a new generation of diagnostics for inflammatory diseases that could lead to earlier diagnosis and to monitor treatment, resulting in large economic and health benefit. It may lead to development of novel new therapies using monoclonal antibodies to regulate processes in immune, cardiovascular and infectious diseases. The work will gene ....Identification of novel markers of inflammation. This project will benefit Australia as it will increase basic understanding of inflammatory processes, result in a new generation of diagnostics for inflammatory diseases that could lead to earlier diagnosis and to monitor treatment, resulting in large economic and health benefit. It may lead to development of novel new therapies using monoclonal antibodies to regulate processes in immune, cardiovascular and infectious diseases. The work will generate significant economic spin-offs to the Australian biotechnology industry and will further relationships and training between research and development.Read moreRead less
Development of an effective vaccine for chlamydial infection: optimisation of a non-toxic cholera toxin-based adjuvant to generate a protective mucosal response. Chlamydial genital infections are the most common sexually transmitted infection in Australia and the world and impose a major health burden on the community. Chlamydial infections are also associated with cardiovascular disease, Australia's biggest killer and asthma, another condition that has increased significantly in prevalence in t ....Development of an effective vaccine for chlamydial infection: optimisation of a non-toxic cholera toxin-based adjuvant to generate a protective mucosal response. Chlamydial genital infections are the most common sexually transmitted infection in Australia and the world and impose a major health burden on the community. Chlamydial infections are also associated with cardiovascular disease, Australia's biggest killer and asthma, another condition that has increased significantly in prevalence in the past 10 years. This project will evaluate the effectiveness of a new adjuvant as a first step towards the development of a vaccine to target these important infections.Read moreRead less
Novel lipid-based adjuvants for induction of mucosal immunity. The project will determine if needle-free oral and transcutaneous immunisation using LipoVax, a novel lipid-based antigen delivery system developed by the industry partner, can protect mice against the mucosal pathogens Chlamydia and Helicobacter. We expect to show that this immunisation method can induce protective mucosal immunity against two of the most common infectious organisms affecting mankind. If successful this will allow u ....Novel lipid-based adjuvants for induction of mucosal immunity. The project will determine if needle-free oral and transcutaneous immunisation using LipoVax, a novel lipid-based antigen delivery system developed by the industry partner, can protect mice against the mucosal pathogens Chlamydia and Helicobacter. We expect to show that this immunisation method can induce protective mucosal immunity against two of the most common infectious organisms affecting mankind. If successful this will allow us to develop LipoVax as a new platform technology that can be applied to the development of human vaccines, veterinary vaccines, vaccines for companion animals and vaccines to target infections in feral animals and native wildlife population populations.Read moreRead less
Enhancing immunogenicity of DNA vaccines by targeted delivery to antigen presenting cells. Vaccines have proven to be one of the most effective means of preventing infection and also provide promise as a treatment for cancer. However, the range of effective technologies that make possible the delivery of vaccines that can protect against a broad range of infections is limited. DNA based vaccines are attractive because they are relatively easy to produce against a wide range of infections. Howeve ....Enhancing immunogenicity of DNA vaccines by targeted delivery to antigen presenting cells. Vaccines have proven to be one of the most effective means of preventing infection and also provide promise as a treatment for cancer. However, the range of effective technologies that make possible the delivery of vaccines that can protect against a broad range of infections is limited. DNA based vaccines are attractive because they are relatively easy to produce against a wide range of infections. However, DNA vaccines often provide poor protection against infections. This project will explore a unique technology developed in Australia and that will greatly improve the effectiveness of DNA vaccines against a broad range of diseases. 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
Toll-like receptors in infectious and inflammatory diseases: the double-edged sword of innate immunity. The innate immune system is the first line of defence against invading microorganisms. This project will explore the role of specific innate immune genes in the control of infections and the development of inflammatory diseases.
Inflammasomes: molecular drivers of anti-microbial defence. The innate immune system is the body’s first line of defence against infection, but also drives unhealthy inflammation. Families of innate immune receptors, such as nucleotide-binding oligomerisation domain (NOD-like Receptors), were recently discovered to control both anti-microbial defence and unhealthy inflammation. This project will characterise the basic biology of NOD-like Receptors at the molecular, cellular and organismal levels ....Inflammasomes: molecular drivers of anti-microbial defence. The innate immune system is the body’s first line of defence against infection, but also drives unhealthy inflammation. Families of innate immune receptors, such as nucleotide-binding oligomerisation domain (NOD-like Receptors), were recently discovered to control both anti-microbial defence and unhealthy inflammation. This project will characterise the basic biology of NOD-like Receptors at the molecular, cellular and organismal levels, and will thereby lead to a greater understanding of the fundamental biological pathways controlling inflammation and defence against infection. This may ultimately lead to commercial opportunities for treating infection and chronic inflammation.Read moreRead less