T-follicular Helper Cell Subsets That Induce Protective Anti-Plasmodium Falciparum Antibodies
Funder
National Health and Medical Research Council
Funding Amount
$456,262.00
Summary
Malaria claims at least half a million lives each year, the majority of them in children under the age of 5 years. In order to development effective vaccines malaria it is critically important that we increase our understanding of the key mechanisms governing the induction of protective immune responses in naturally exposed populations. This project will examine the role of one important cell subset - T-follicular helper cells - in the development of immunity against malaria.
Determining The Role Of DOCK8 In CD4+ T And B Cell Differentiation And Its Implications On Autosomal Recessive Hyper IgE Syndrome (AR-HIES)
Funder
National Health and Medical Research Council
Funding Amount
$512,600.00
Summary
Autosomal recessive hyper IgE (AR-HIES) syndrome due to mutations in DOCK8 is a rare primary immunodeficiency whereby patients present with susceptibility to severe and recurrent viral infections as well as an increased risk of developing cancer, severe food and environmental allergies, and atopic disease characterised by hyper IgE and extreme eosinophilia. This grant will investigate how abnormal DOCK8 function in CD4+ T cells and B cells contributes to disease pathogenesis in AR-HIES patients.
Understanding The Role Of CD4 T Cells In Viral Infection: A Means Of Improving Anti-viral Immunotherapy.
Funder
National Health and Medical Research Council
Funding Amount
$672,009.00
Summary
Development of therapies to prevent and treat chronic infections is of the highest priority as they cause considerable clinical challenges and on-going health care costs. Efforts to improve treatment of chronic viral infections, such as those caused by HIV, hepatitis C virus and human cytomegalovirus, require a better understanding of the immune responses needed to control these viruses long-term. This proposal will investigate the role of CD4+ T cells in controlling chronic viral infection.
Envelope Glycoprotein Determinants Of HIV-1 Subtype C Tropism And Pathogenicity
Funder
National Health and Medical Research Council
Funding Amount
$657,745.00
Summary
HIV-1 subtype C is the most common subtype of HIV-w worldwide, yet we know comparatively little about how it causes disease in humans. This study will elucidate how HIV-1 subtype C evolves in patients to become more pathogenic over time.
Using Single-cell Genomics To Resolve Functional Diversification By CD4+ T Cells In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$1,048,096.00
Summary
During immune responses, individual CD4+ T cells multiply and produce hundreds of descendants, with close relatives within a family often developing very different skills. How such differences emerge from one ancestor remains unclear. We use new methods to look at individual CD4+ T cells in unprecedented detail, allowing us to see how close relatives begin to grow apart. Using this, we hope to find novel ways of educating CD4+ T cells to prevent infectious and immune-mediated diseases.
HIV-1 Transcriptional Gene Silencing By Promoter Targeted Si/shRNAs: Uncovering Mechanisms, Optimising Delivery Systems, Assessing In Vivo Efficacy.
Funder
National Health and Medical Research Council
Funding Amount
$641,789.00
Summary
Current therapy for HIV is effective but must be taken for life. If therapy is stopped the virus comes back immediately from reservoirs not affected by current drugs. These fluctuating levels of virus are associated with increased illness and death. We are exploring a method of inducing prolonged viral latency using short double stranded RNA molecules. We propose to understand the mechanism of action of these possible therapeutics and to develop these constructs towards use in clinical trials.
The Molecular Basis Of Human CD4+ T-cell Responses In Autoimmune Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$656,498.00
Summary
Over 120,000 Australians currently suffer from type 1 diabetes. This incurable disease typically strikes in childhood or adolescence and is caused by the immune system destroying the cells which make insulin. This project aims to determine how and why the insulin producing cells are recognized by the immune system. Eventually this work will lead to new vacccines to prevent the immune system from destroying the insulin producing cells.
Reduced HIV Infection And Increased Survival Among HIV-exposed Infants Using Two Newly Developed Point-of-care Tests In Papua New Guinea And China.
Funder
National Health and Medical Research Council
Funding Amount
$952,841.00
Summary
HIV contributes significantly to maternal and infant deaths, largely due to limited access to effective antiretroviral drugs among HIV-infected expectant mothers and their HIV-infected infants. Decisions on what and when to start treatment currently depends on sophisticated laboratory tests, unavailable to many. This research is a world-first intervention study to assess the effectiveness and impact of two newly developed and unique low-cost rapid point-of-care tests.
Clinical Implications Of IL7R Genotype: From Disease Risk To Disease Management
Funder
National Health and Medical Research Council
Funding Amount
$627,765.00
Summary
We’ve identified a genetic test (IL7R?) that may predict and prevent the risk of patients (i) failing to respond adequately to treatment for HIV (ii) who are at high risk of death after bone marrow transplantation and (iii) who fail to respond to interferon treatment for MS. This project aims to confirm these in very large patient groups and uncover the cellular basis for the genetic effect. Our goal is to provide a novel test that will improve patient outcomes in 3 serious disease states.
Characterisation Of Eurl, A Novel Gene Implicated In The Etiology Of Abnormal Brain Development And Intellectual Disability
Funder
National Health and Medical Research Council
Funding Amount
$597,541.00
Summary
Intellectual disability affects around one per cent of Australians, and can arise from genetic abnormalities during fetal life, such as through abnormal regulation of gene expression. We have identified a novel gene, known as eurl, which controls brain assembly as well as the ability of neurons to form functional connections within the brain. We will investigate how this novel gene controls brain development, and characterise eurl as a potential therapeutic target for learning and memory.