Identification Of Molecular And Cellular Pathways Predicting Susceptibility Or Resistance To Severe Dengue Fever
Funder
National Health and Medical Research Council
Funding Amount
$761,481.00
Summary
This cooperative research project aims to undertake a comprehensive immunological and molecular analysis of individuals with mild versus severe dengue fever recruited at local hospitals in Jakarta, Indonesia. The project will uncover key processes responsible for the development of severe disease. This information will identify specific biomarkers for innovative diagnostic tools for early prediction/detection of cases that will progress to complicated dengue.
Novel Posttranscriptional Pathways The Control Tfh Cell Numbers
Funder
National Health and Medical Research Council
Funding Amount
$647,539.00
Summary
T follicular helper (Tfh) cells are essential for effective antibody responses against infection. Limiting Tfh cells is crucial for selecting the "fittest" B cells and the success of vaccines. Tfh cell accumulation causes autoimmuity and is associated with inadequate B cell responses in HIV infection. We have recently discovered two novel pathways that control Tfh cells. We speculate they regulate different RNAs that influence Tfh homeostasis and aim to elucidate their mechanism of action.
It is feasible to sequence patient genomes but we need to know more about how genetic variants cause complex disease. We have sequenced genomes from patients with immune deficiency and will test the idea that genetic variation causes consistent changes in particular white blood cells, thus providing a bridge between genomic information and clinical diagnosis. Outcomes will include more accurate diagnosis, better understanding of immunity, and a strategy for using whole genome information.
A Novel Role For MHC Class II In Carbohydrate Presentation
Funder
National Health and Medical Research Council
Funding Amount
$703,030.00
Summary
Cells of the immune system swallow up foreign molecules and break them down to smaller fragments. T cells then identify the degraded antigen fragments and coordinate the immune response. In this project we will investigate how the T cells identify carbohydrates.
Understanding Immunity To Influenza B Viruses For A Rationally Designed Universal Vaccine
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
Influenza B viruses (IBV) circulate annually and are particularly prevalent and severe in children. However, IBV remain largely understudied. Our immune system provides protection against IBV via a variety of mechanisms. This study will characterize the immunity to IBV and dissect host-virus interactions which provide protection from IBV infection. This project will inform the rational design of novel vaccines eliciting universal immunity to IBV, with an ultimate goal of controlling IBV.
Development Of CD96 Antibodies For Cancer Treatment
Funder
National Health and Medical Research Council
Funding Amount
$820,821.00
Summary
There is an unmet medical need to develop new immunotherapies that are safer and potentially allow the treatment of a broader range of cancers. Inhibiting the immune checkpoint CD96 function represents an opportunity that may parallel and indeed complement the activity and impact of other lymphocyte checkpoint inhibitors in human cancer (eg. CTLA-4 and PD1/PD-L1). While developing a new human therapeutic antibody we will also learn more about an important checkpoint in the immune response.
Immunodominance And Protective Immunity In The Context Of A Complex Host-pathogen System.
Funder
National Health and Medical Research Council
Funding Amount
$899,832.00
Summary
In experimental infection models with simple organisms, pathogen-specific immune responses recognize only a small fraction of potential epitopes encoded by the genome. This phenomenon is termed immunodominance. We propose the first comprehensive study of immunodominance in humans in response to a complex pathogen, the Plasmodium parasite that causes malaria. This will provide valuable new knowledge of host-pathogen immunity and facilitate rational vaccine design.
Immunological Diseases: Understanding Their Cause And Improving Their Treatment By Human Genome Sequencing
Funder
National Health and Medical Research Council
Funding Amount
$788,486.00
Summary
Prof Goodnow will develop a collaborative consortium of specialist physicians, laboratory researchers and bioinformaticians. This team will apply the new tools of large scale DNA sequencing to reveal the root cause of immune system diseases including: autoimmune diseases, congenital immune deficiency diseases, allergic disorders, and cancer. It aims to accelerate, simplify and unify the diagnosis of these diseases, and guide targeted, earlier and more effective treatment.
Control Of Pathogenic Antibody Responses In Humans
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
Deficient or inappropriate antibody responses are at the core of many autoimmune diseases, allergies, food intolerances, and often explain the failure of vaccination strategies. Specialised follicular T cells control the quality of antibodies produced by B cells. This fellowship will combine basic studies investigating B cell helper or regulatory follicular T cells in humans with genetic studies identifying the causes of autoantibody-driven diseases. The results will uncover targeted therapies.