I am a viral immunologist studying the requirements for an effective host response to viral infection. I am also investigating the potential for the development of efficacious vaccines to protect against infection and ways of intervening in the disease pr
Intraepithelial lymphocyte development and function in the intestine. This study aims to better understand the homeostatic maintenance and essential repair processes in the intestine. This project will generate new knowledge of how immune cells of the intestine, known as intraepithelial lymphocytes (IELs), engage with intestinal epithelial cells, neurons and commensal microbes to promote homeostasis and repair. Expected outcomes of this project will be identification of new molecules for future ....Intraepithelial lymphocyte development and function in the intestine. This study aims to better understand the homeostatic maintenance and essential repair processes in the intestine. This project will generate new knowledge of how immune cells of the intestine, known as intraepithelial lymphocytes (IELs), engage with intestinal epithelial cells, neurons and commensal microbes to promote homeostasis and repair. Expected outcomes of this project will be identification of new molecules for future drug and vaccine development to improve gut health and vaccination in mammals. This should provide significant benefits to the Australian population and livestock industry through improved protection against cancer, intestinal infections and increased productivity. Read moreRead less
HIV currently infects ~40 million people world-wide, causing ~3 million deaths in 2003, mainly in the world's poorest countries. A cheap, effective vaccine seems the best means of preventing the spread of the epidemic. The two main approaches to vaccination are either to make antibodies (which bind to and inactivate the virus), or killer T cells (which kill infected cells). Many of these vaccines are now being tested in monkeys. The results of killer T cell vaccination trials have been both enco ....HIV currently infects ~40 million people world-wide, causing ~3 million deaths in 2003, mainly in the world's poorest countries. A cheap, effective vaccine seems the best means of preventing the spread of the epidemic. The two main approaches to vaccination are either to make antibodies (which bind to and inactivate the virus), or killer T cells (which kill infected cells). Many of these vaccines are now being tested in monkeys. The results of killer T cell vaccination trials have been both encouraging and disappointing. The vaccines do not appear able to prevent the monkeys from getting infected with the virus. However, in many cases even though the monkeys become infected with HIV, they do not get the usual disease associated with AIDS, and hence live with rather than die from this infection. The aims of this project are to use statistical analysis, and more complex mathematical and computer models to try to analyse the data generated by these vaccine trials and to understand how these partially effective vaccines help control virus. For example, even if a vaccine does not prevent infection, we can investigate whether it slowed viral growth, or increased killing of infected cells, and if so, whether an increase in this response could be effective. In preliminary work we have analysed data from a vaccination trial performed in Boston. The results of this study suggest that the reason vaccinated monkeys still become infected is that the killer T cells produced by the vaccine do not appear to activate for the first 10 days of infection. In these first 10 days the virus grows normally and is able to establish a foothold for continuing infection. By contrast, we find that antibodies act extremely early after infection. The methods we propose have not been used before to study vaccines, and by studying the kinetics of the virus and immune response from a large number of vaccine trials we hope to help identify the optimal vaccine design.Read moreRead less
Histone deacetylase functions in immune cells. This project aims to define how an enzyme (a histone deacetylase) enables innate immune cells (macrophages) to respond to specific danger signals, such as those activating Toll-like Receptors. To identify processes that provide specificity to signal transduction pathways, this project will characterise protein targets and biological functions of a specific class IIa histone deacetylase in macrophages. This project expects to result in an understandi ....Histone deacetylase functions in immune cells. This project aims to define how an enzyme (a histone deacetylase) enables innate immune cells (macrophages) to respond to specific danger signals, such as those activating Toll-like Receptors. To identify processes that provide specificity to signal transduction pathways, this project will characterise protein targets and biological functions of a specific class IIa histone deacetylase in macrophages. This project expects to result in an understanding of histone deacetylases and protein deacetylation in immune cell responses which can be harnessed to manipulate cell functions for basic science and biotechnology uses.Read moreRead less
Regulation of lung immune-epithelial networks sensing environmental change. This study aims to uncover how lung epithelial cells engage with immune cells and determine their cellular and molecular wiring to ensure homeostatic maintenance and essential repair processes of lung tissues. Maintenance of lung epithelial-immune networks is essential to maintain normal lung tissue structure and function, and to induce immune responses to protect against microbial challenges or inhaled potentially toxic ....Regulation of lung immune-epithelial networks sensing environmental change. This study aims to uncover how lung epithelial cells engage with immune cells and determine their cellular and molecular wiring to ensure homeostatic maintenance and essential repair processes of lung tissues. Maintenance of lung epithelial-immune networks is essential to maintain normal lung tissue structure and function, and to induce immune responses to protect against microbial challenges or inhaled potentially toxic substances. Understanding this molecular program of epithelial-immune cell-mediated sensing/repair will be essential to understand how tissue-repair processes can be driven in the lung, an organ critical for respiration and thus life.Read moreRead less
Immune Regulation, Effector Function And Human Therapy
Funder
National Health and Medical Research Council
Funding Amount
$11,474,346.00
Summary
The immune system plays an important role in protecting the host from viral and bacterial infections, and inhibits cancer onset and progression. Immune processes proceed through specialised cells in conjunction with soluble factors such as inteferons and interleukins. These soluble factors can regulate the activities of immune cells, and inhibit the growth and survival of aberrant (virus infected, cancer) cells. Unfortunately, the immune system can sometimes lose specificity and attack the host, ....The immune system plays an important role in protecting the host from viral and bacterial infections, and inhibits cancer onset and progression. Immune processes proceed through specialised cells in conjunction with soluble factors such as inteferons and interleukins. These soluble factors can regulate the activities of immune cells, and inhibit the growth and survival of aberrant (virus infected, cancer) cells. Unfortunately, the immune system can sometimes lose specificity and attack the host, resulting in autoimmune diseases such as diabetes. This research team has played a vital role in characterising the specific activities of immune cells and the associated factors. Importantly, they are deciphering the intricate communication networks of these immune components and dissecting their modes of action. By understanding these complex processes, the team aims to harness the unique therapeutic properties of our own immune system and translate their findings into the clinic. The team is developing new immune-based therapies for use, either alone or in combination with existing chemotherapies to fight debilitating human diseases such as cancer and autoimmune disease.Read moreRead less
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE140100070
Funder
Australian Research Council
Funding Amount
$650,000.00
Summary
An advanced in vivo imaging facility. An advanced in vivo imaging facility: This project will establish an advanced In Vivo Imaging Facility (IVIF) for examining host-microbe interactions and associated immunological processes within the context of the numerous infectious disease models within the University of Melbourne and associated collaborators. The Zeiss LSM 7MP 2-photon imaging system will provide enhanced capacity to directly visualise cellular and molecular events in real time, with gre ....An advanced in vivo imaging facility. An advanced in vivo imaging facility: This project will establish an advanced In Vivo Imaging Facility (IVIF) for examining host-microbe interactions and associated immunological processes within the context of the numerous infectious disease models within the University of Melbourne and associated collaborators. The Zeiss LSM 7MP 2-photon imaging system will provide enhanced capacity to directly visualise cellular and molecular events in real time, with greater sensitivity and in a broader range of tissues and organs. This will provide the opportunity for novel insights into numerous immunological and host-microbe interactions.Read moreRead less
The world has suddenly been alerted to the threat of pandemic influenza with the recent deaths in Asia of patients and their close contacts from which the avian influenza H5N1 virus has been isolated. Experts believe that it is only a matter of time before this virus mutates and acquires the ability to rapidly spread within the human population. The currently available vaccines have virtually no capacity to prevent infection by a new pandemic virus. Once the virus strikes appropriate vaccines ca ....The world has suddenly been alerted to the threat of pandemic influenza with the recent deaths in Asia of patients and their close contacts from which the avian influenza H5N1 virus has been isolated. Experts believe that it is only a matter of time before this virus mutates and acquires the ability to rapidly spread within the human population. The currently available vaccines have virtually no capacity to prevent infection by a new pandemic virus. Once the virus strikes appropriate vaccines can be made against it but this procedure takes at least 6 months, the time predicted for the virus to have already spread throughout the globe. We are proposing that a vaccine designed to induce killer T cells (called CTLs) that target the conserved regions shared by all influenza viruses, could be used as a preventative measure without prior knowledge of the exact type of virus that will emerge. This sort of vaccine will not prevent against infection but will greatly lessen the severity of the disease. We have already designed a vaccine that that will induce high levels of CTLs that can greatly speed up the clearance of viruses of the type that are currently in the human population, when tested in animal models. However, we predict that a new pandemic virus will be much more vigorous in its growth and so our vaccines will have to be improved to cope with this. This project looks at ways of increasing the number and effectiveness of the CTLs that are induced by our vaccines. This will require an understanding of how we can modulate the function of other specialised cells, dendritic cells and helper T cells, that play a role in starting and maintaining the CTL response, as well as modulating the CTLs themselves.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.