Protecting Against Malaria Through Liver-resident Memory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,196,853.00
Summary
We have shown that formation of liver-resident memory T cells (Trm), a newly discovered type of immune cells, can be induced by an innovative vaccination strategy called prime and trap for highly efficient protection against malaria in mice. Here, we will enhance prime and trap vaccination efficacy by defining the conditions that maximize liver Trm-mediated protection and will characterize simian and human liver Trm cells, paving the way to create the most efficient human malaria vaccine to date
Deciphering How TCR Affinity Regulates CD4 T Cell Help In Immunity And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$850,885.00
Summary
Immune responses require the coordinated interaction and cross-talk between two types of white blood cells known as CD4 and CD8 T cells. A dysregulated interaction between these cells could be the cause of autoimmune and persistent infections by pathogens leading to chronic diseases. The aim of this proposal is to provide a deeper understanding of CD4/CD8 T cell interactions to improve immune outcomes in many chronic diseases in which interaction between these two immune cells is critical.
Initial Interactions Of Herpes Simplex Virus With Innate Immune Cells In Human Skin
Funder
National Health and Medical Research Council
Funding Amount
$522,589.00
Summary
Herpes simplex viruses 1 and 2 cause widespread and occasionally serious diseases including genital herpes, neonatal death and encephalitis. Current vaccine candidates are at best partially effective. This grant will examine the way that the virus enters, initially spreads within the skin and interacts with immune cells to help determine which cells should be stimulated by vaccines.
The Unique Nature Of Gamma Delta T Cell Recognition Resolved Through Interaction With H2-Q10
Funder
National Health and Medical Research Council
Funding Amount
$699,031.00
Summary
The liver is important for both digestion and immunity. Given these opposing functions, the liver must exert control points that prevent the immune system from recognising food products. We have now identified a new molecular target that controls the development of immune cells in the liver.
Deciphering Mechanisms Of Liver Allograft Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$520,964.00
Summary
The liver has paradoxical properties: it is the site of effective immune responses to pathogens, but under some circumstances, it is known to induce harmless immune responses. Liver transplants are more readily accepted than other organ grafts in the absence of immunosuppressive drugs but little is known about the mechanisms that prevent an effective response. This proposal aims to unravel these mechanisms. This project will have important implications for transplantation studies.
Elucidation Of Immune Mechanisms Underlying HSV Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$573,993.00
Summary
HSV-1 and -2 causes genital herpes, cold sores, encephalitis, potential fatal neonatal herpes, keratitis and blindness as well as severe disease in transplant patients. HSV infection also enhances the acquisition of HIV by 2-3 fold. Investigating the mechanism of immune response to HSV infection or components of HSV will assist in understanding immune control of HSV, HSV vaccine development, and assist in reducing in HIV spread.
The Role Of Chemokines In Establishing HIV Latency
Funder
National Health and Medical Research Council
Funding Amount
$372,049.00
Summary
Although antiviral therapy is effective in controlling HIV, therapy must be continued life-long because the virus cannot be cleared from long lived infected CD4+ T cells that are silently or latently infected. In this proposal we will explore the mechanism of how HIV can enter these resting CD4+ T-cells and establish long lived latent infection. Understanding this process may potentially lead to new strategies to cure HIV infection.
The Extinction Of Conditioned Fear And Its Implications For Cue Exposure Therapy
Funder
National Health and Medical Research Council
Funding Amount
$322,430.00
Summary
This project studies extinction of Pavlovian conditioned fear reactions in rats. Extinction of these reactions is an animal model for exposure therapy used in the treatment of anxiety disorders in people. In exposure therapy, the patient, aided by the clinician, confronts trauma-related cues in the absence of any overt danger. The intention of this therapy is to reduce the ability of the trauma-related cues to provoke the fear reactions that are undermining the patient's quality of life. In Pavl ....This project studies extinction of Pavlovian conditioned fear reactions in rats. Extinction of these reactions is an animal model for exposure therapy used in the treatment of anxiety disorders in people. In exposure therapy, the patient, aided by the clinician, confronts trauma-related cues in the absence of any overt danger. The intention of this therapy is to reduce the ability of the trauma-related cues to provoke the fear reactions that are undermining the patient's quality of life. In Pavlovian conditioning, subjects (typically rats) are exposed to a signaling relation between an initially neutral stimulus (e.g., a noise) and a feared outcome (e.g., foot shock). When later repeatedly exposed to the initially neutral but now feared stimulus (the noise) in the absence of the feared outcome, the fear reactions it acquired progressively decline until eventually it fails to elicit any such reactions. The fear reactions are said to have been extinguished. There has been significant progress in understanding the psychological processes and neural mechanisms underlying the acquisition of fear reactions, but much less is known about the processes and mechanisms underlying the extinction of these reactions. The project has two general objectives. The first is to determine the conditions of extinction training that promote long-term loss of fear reactions. The second objective is to determine how the brain controls this extinction of learned fear. Achieving these aims will be significant for two reasons. First, it will contribute to understanding the mechanisms by which animals (including people) learn to adjust their behaviour to bring it into line with the current relations that exist between events in the world. Second, it will provide important information about how such adjustment is facilitated or impaired across extinction training and, thereby, contribute towards understanding both the successes and failures of cue exposure therapy for fear-related disorders.Read moreRead less
The Biology Of Events Following Reactivation Of Herpes Simplex Virus.
Funder
National Health and Medical Research Council
Funding Amount
$388,522.00
Summary
Herpes simplex virus causes genital herpes, severe disease in neonates, cold sores and occasionally fatal encephalitis. It lies doemant within nerve cells near the spine and reactivates intermittently, travelling down nerves to cause the characteristic ulcers in the skin, including the genitals. This grant has two major components. In the first we aim to continue studies which are defining the way in which Herpes simplex viruses assemble within nerve cells. These processes have always been the s ....Herpes simplex virus causes genital herpes, severe disease in neonates, cold sores and occasionally fatal encephalitis. It lies doemant within nerve cells near the spine and reactivates intermittently, travelling down nerves to cause the characteristic ulcers in the skin, including the genitals. This grant has two major components. In the first we aim to continue studies which are defining the way in which Herpes simplex viruses assemble within nerve cells. These processes have always been the subject of much debate and have never been properly studied in the nerve cells in which the virus lives. Furthermore the way in which herpes simplex virus enters the processes of nerve cells and moves to the cell body will be studied by similar techniques. Such studies may contribute to the development of herpes simplex virus as a vector for gene therapy for treatment of diseases of the nervous system. The second part of the grant will examine the immune processes that occur in the skin during the early stages of a recurrent herpes simplex lesion. In particular there is a linkage between nerves and the major cells in the skin which present viral antigen to defensive T-cells. This link may provide a route for direct access of herpes simplex virus to these cells. In previous work the viral protein targets in infected skin cells for killer T-cells which infiltrate the skin have been defined. In this grant we also aim to find the stretches of amino acids which are specifically targetted by these cells.Read moreRead less
Unravelling A New Fatty Acid Pathway Involved In Neuroexocytosis And Memory
Funder
National Health and Medical Research Council
Funding Amount
$539,631.00
Summary
This proposal build on the establishment by our laboratory of the assay capable of detecting free fatty acids, with great accuracy and sensitivity. Using this assay we have uncovered a completely new pathway highlighting the production of saturated free fatty acids linked to learning and memory. We will fully define how this pathway is regulated in the brain.