I am an immunologist focusing on understanding how can we combat chronic infections while preventing autoimmunity. This proposal aims to investigate how a poorly understood subset of lymphocytes called Tfh cells are regulated to promote the formation of protective antibodies, and prevent development of harmful antibodies that go on to cause or exacerbate diseases such as lupus, rheumatoid arthritis and type 1 diabetes. Our discoveries will illuminate novel drug targets for these diseases and hel ....I am an immunologist focusing on understanding how can we combat chronic infections while preventing autoimmunity. This proposal aims to investigate how a poorly understood subset of lymphocytes called Tfh cells are regulated to promote the formation of protective antibodies, and prevent development of harmful antibodies that go on to cause or exacerbate diseases such as lupus, rheumatoid arthritis and type 1 diabetes. Our discoveries will illuminate novel drug targets for these diseases and help generate more potent vaccines.Read moreRead less
The Role Of Rip3 And Caspase 8 In Necroptosis And Apoptosis During Viral Infection
Funder
National Health and Medical Research Council
Funding Amount
$459,499.00
Summary
Programmed cell death can be beneficial or detrimental depending on circumstances. This delicate balance is most obvious during an infection. The host tries to limit the spread of a pathogen by initiating programmed death in infected cells but excessive death particularly in uninfected cells is catastrophic. It is essential to have a thorough understanding of the interplay between cell death mechanisms so we can overt pathological outcomes and this is the focus of our research.
Cell Pedigree Tracking To Elucidate How Polarity Proteins Alter Fate In B-cell Development And Leukaemia.
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
During the onset of cancer, the orientation of cells is lost. My research project aims to determine the cellular and molecular basis by which proteins responsible for the orientation of cells are involved in leukaemia. Additionally, my work will investigate whether or not all proteins are equally distributed during cell division in B cell development, and will provide a platform for further investigation into how protein distribution might orchestrate fate decisions during development and leukae ....During the onset of cancer, the orientation of cells is lost. My research project aims to determine the cellular and molecular basis by which proteins responsible for the orientation of cells are involved in leukaemia. Additionally, my work will investigate whether or not all proteins are equally distributed during cell division in B cell development, and will provide a platform for further investigation into how protein distribution might orchestrate fate decisions during development and leukaemia.Read moreRead less
Regulating The Production Of High Affinity Antibody Forming Cells During The Germinal Centre Reaction.
Funder
National Health and Medical Research Council
Funding Amount
$376,980.00
Summary
In response to infection the body makes antibodies. These antibodies are important in helping clear the infection and keeping us healthy. What's more, the immune system 'remembers' these past infections. This means that when we are re-exposed to an infectious agent like measles virus, no disease develops. This is because the antibodies which cleared the infection initially, are still being made and prevent or neutralize the new infection or toxin. The continued production of these antibodies is ....In response to infection the body makes antibodies. These antibodies are important in helping clear the infection and keeping us healthy. What's more, the immune system 'remembers' these past infections. This means that when we are re-exposed to an infectious agent like measles virus, no disease develops. This is because the antibodies which cleared the infection initially, are still being made and prevent or neutralize the new infection or toxin. The continued production of these antibodies is therefore an important part of staying healthy. When we are vaccinated, we produce antibodies specific for the components of the vaccine. Some of these components are part of the real infectious agent. This means that when we encounter the real virus, we already have antibodies that prevent the virus from doing any damage. Booster immunizations are necessary to make sure we have high enough levels of these neutralizing antibodies. Being able to understand how these important antibodies are made is a central goal of this research project. We hope that by understanding how cells are durected in an immune response to become the kind of cells that secretes neutralizing antibodies, we will be able to make vaccines that work more efficiently, that require fewer booster injections and that give longer lasting protection. We also hope that we can better design vaccines so that those that currently don't work, can be made to do so.Read moreRead less
Towards A Functional Cure For HBV: Exploiting Lessons From HBV-HIV Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$913,551.00
Summary
Hepatitis B virus (HBV) infection can be treated, but therapy is usually lifelong and has side effects, so a cure for HBV is very important. We work closely with colleagues in Asia where both HBV and HIV are common so this provides a unique opportunity to study HBV. We will investigate how an effective immune response against the 2 main HBV proteins is developed. If we can understand how the immune response works against HBV, this could be used to develop new therapies to develop a cure for HBV
Analysis Of Antigen Receptor Sharing By T And B Lymphocytes
Funder
National Health and Medical Research Council
Funding Amount
$540,356.00
Summary
To survive an infection the immune system must rapidly expand the number of immune cells that have pathogen-specific receptors that recognise, and therefore specifically combat, the infection. This normally occurs through proliferation of the immune cells. We have found that in addition to proliferation, the number of cells with these receptors can be increased by a process of receptor transfer between cells. This grant aims to further advance our understanding of this novel phenomenon.
Hepatitis B Virus Immunity In Indigenous And At Risk Children Who Received Hepatitis B Vaccination In Infancy
Funder
National Health and Medical Research Council
Funding Amount
$213,762.00
Summary
Hepatitis B virus (HBV) is transmitted by blood exposure or sexual contact and infection can result in chronic liver disease and liver cancer. Since 2000 Hepatitis B virus immunisation has been recommended for all infants in Australia with the first dose given at birth. However, prior to routine universal immunisation, a selective immunisation strategy was used in Australia from 1986. This targeted infants considered at high risk of HBV infection because of high prevalence in their population of ....Hepatitis B virus (HBV) is transmitted by blood exposure or sexual contact and infection can result in chronic liver disease and liver cancer. Since 2000 Hepatitis B virus immunisation has been recommended for all infants in Australia with the first dose given at birth. However, prior to routine universal immunisation, a selective immunisation strategy was used in Australia from 1986. This targeted infants considered at high risk of HBV infection because of high prevalence in their population of origin, (including Aboriginal- Torres Strait Islanders) and infants whose mother was a HBV carrier. These children, among the first to be vaccinated, are now adolescents. There have been no long-term follow-up studies in Australia, and limited studies elsewhere, to assess the extent of breakthrough infection and persistence of immunity to Hepatitis B after vaccine at birth. As onset of sexual activity is associated with an increased exposure to hepatitis B infection, booster doses may be needed, especially in high-risk individuals. This study includes 2 high risk groups - young indigenous adults in the Northern Territory and young adults born to HBV carrier mothers in central Sydney. It will measure the number of children who have been infected with HBV or are chronic carriers, compared to pre immunisation data, and also the persisting level of immunity in children who were vaccinated against HBV as an infant. Children whose blood test indicates that they have low immunity will be given a booster dose of HBV vaccine and their immune response measured. A rise in hepatitis B antibody following booster vaccination indicates that you have immunological memory and is currently considered to show protection from natural hepatitis B infection. If clinically significant HBV infections are found to be rare and immunologic memory can be demonstrated, this would provide good evidence to support the argument that booster vaccine doses are not required in the Australian context.Read moreRead less
The Role Of Mal In Toll-like Receptor Signal Transduction Of The Pro-inflammatory Response.
Funder
National Health and Medical Research Council
Funding Amount
$472,500.00
Summary
Sepsis kills more people per year than the cancers of the breast, colon, prostate and pancreas combined. Sepsis occurs in 1 of 50 hospital admissions and is the leading cause of death n intensive care units. The instance of sepsis has doubled in the last decade and is expected to increase. One of the major causes of sepsis si lipopolysaccharide (LPS), the main constituent of gram-negative bacteria's cell wall, and the prototypic inducer of the pro-inflammatory response of the innate immune syste ....Sepsis kills more people per year than the cancers of the breast, colon, prostate and pancreas combined. Sepsis occurs in 1 of 50 hospital admissions and is the leading cause of death n intensive care units. The instance of sepsis has doubled in the last decade and is expected to increase. One of the major causes of sepsis si lipopolysaccharide (LPS), the main constituent of gram-negative bacteria's cell wall, and the prototypic inducer of the pro-inflammatory response of the innate immune system. Dysregulation of the pro-inflammatory response can lead to sepsis. Recently, the mammalian receptor for LPS was found to be Toll-like receptor (TLR)-4, the activation of which activates a signal transduction pathway that initiates the pro-inflammatory response. We have previously shown a key role for an adapter protein called Mal in mediating signal transduction pathways upon activation of TLR-4. Interaction of Mal with a key signal transduction mediator called TRAF6 has been shown to induce the activation of the pro-inflammatory response. Furthermore, Mal has been found to undergo degradation which may indicate a means of regulating the continued activation of the pro-inflammatory pathway. This research program will investigate the role of Mal in mediating signal transduction in TLR activated macrophages, key responsive cells of the innate immune system to microbial infection. A greater understanding of these processes will assist in the development of therapeutics to alleviate the consequences of microbial-induced inflammation, including chronic inflammatory diseases and sepsis.Read moreRead less