Intrinsic Host Antiviral Activity Against Pathogenic Filoviruses
Funder
National Health and Medical Research Council
Funding Amount
$488,754.00
Summary
Bats are a major reservoir for deadly human viruses including Ebola and Marburg virus. In contrast to humans, bats can be infected with these viruses without showing clinical signs of disease. The reason why bats can co-exist with these viruses is unknown. This study will determine if a bat antiviral molecule contributes to limiting virus release compared to the human version that could reveal strategies to prevent and control these deadly viruses in humans.
Many infants and children suffer from bowel motility disorders, for example, chronic constipation affects up to 1 in 10 children. However, the cause of many of these paediatric motility disorders remains unknown. In this project, we will examine the development of wiring of the nervous system that controls bowel motility. This is the first study to investigate the development of cell-cell communication during early stages of nervous system development.
The Role Of Co-signalling Receptors In Cytotoxic Lymphocyte Activity During Infection And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$739,657.00
Summary
Cytotoxic lymphocytes (CLs) are immune cells that detect and kill cancer cells. CLs recognise ‘stress’ proteins on cancer cells through specialised receptors, and this provides the signal for them to kill. However, some cancer cells, such as leukemic cells, can interfere with this recognition to avoid killing by immune cells. This project will investigate the mechanism of recognition and killing of cancer cells by CLs, using both mouse models and cells from patients with acute myeloid leukemia.
Harnessing Tyrosine Metabolism To Combat Respiratory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$866,467.00
Summary
Cross-talk between our immune system and the microbiome is central to health and disease. In particular, the gut microbiome has wide-ranging effects throughout the body, in part through the production of metabolites with immunomodulatory activity. We have discovered a novel subset of microbial metabolites which can protect mice against allergic airway inflammation, a model of asthma. We now aim to discovery how these metabolites work with a view towards developing them as therapeutics.
THE IMMUNOLOGICAL LEGACY OF OBESITY ON VIRAL PATHOGENESIS
Funder
National Health and Medical Research Council
Funding Amount
$652,275.00
Summary
Obesity is a key risk factor for severe viral infections. Our preliminary data suggest that in mice this susceptibility is not reduced by weight loss. In this grant we will investigate a) the mechanisms driving the legacy effect of obesity on antiviral immunity b) whether or not we can reverse this legacy effect by treatment with the drug MCC950 and c) the antiviral response of overweight children and adults who have and haven't recently lost weight.
Understanding Influenza-specific T Cell Immunity In The Indigenous Population
Funder
National Health and Medical Research Council
Funding Amount
$870,112.00
Summary
Hospitalisation and death rates from influenza are high in the Indigenous population. There is an urgent need for one-shot universal vaccine that protects against seasonal and pandemic strains. T cells recognising conserved viral regions can elicit such protection. As T cells are restricted by proteins called HLAs, variable between different ethnicities, we will define T cell regions and their HLA restrictions in the Indigenous population to propose strategies for universal T cell-based protecti ....Hospitalisation and death rates from influenza are high in the Indigenous population. There is an urgent need for one-shot universal vaccine that protects against seasonal and pandemic strains. T cells recognising conserved viral regions can elicit such protection. As T cells are restricted by proteins called HLAs, variable between different ethnicities, we will define T cell regions and their HLA restrictions in the Indigenous population to propose strategies for universal T cell-based protective immunity and vaccine design against influenza.Read moreRead less
Dissecting The Central Organisation Of Cough Neural Networks
Funder
National Health and Medical Research Council
Funding Amount
$880,928.00
Summary
Cough is the most prevalent symptom of lung disease and the most common reason for people to seek medical advice. However, cough neural processes are poorly defined and as a result current cough therapies are largely ineffective making cough a significant unmet clinical problem. This project will novel viral strategies to dissect and manipulate cough neural pathways in the brain, providing insights into the neural processing of airway sensations and coughing.
Viral Infection And TGFbeta Impair Glucocorticoid Activity In Epithelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$617,699.00
Summary
Chronic inflammatory lung diseases like asthma and smokers lung are treated with combinations of anti-inflammatory drugs. Powerful anti-inflammatory types of steroid drugs are used in more severe disease. Even these powerful drugs are sometimes not effective enough. Our work is developing an understanding of how inflammation limits the anti-inflammatory effects of steroids and we are devising ways to overcome this with new drugs. We aim to improve treatment of chronic inflammatory diseases, espe ....Chronic inflammatory lung diseases like asthma and smokers lung are treated with combinations of anti-inflammatory drugs. Powerful anti-inflammatory types of steroid drugs are used in more severe disease. Even these powerful drugs are sometimes not effective enough. Our work is developing an understanding of how inflammation limits the anti-inflammatory effects of steroids and we are devising ways to overcome this with new drugs. We aim to improve treatment of chronic inflammatory diseases, especially those affecting the lung.Read moreRead less
How Do Cross-reactive Memory B Cells Affect Influenza Vaccine Titers?
Funder
National Health and Medical Research Council
Funding Amount
$798,049.00
Summary
Influenza vaccines are updated frequently to protect against the highly variable influenza virus. Despite careful selection of vaccine viruses, most influenza vaccines provide only modest protection and protection is poor some years. In turn, the response to vaccination varies between individuals. This probably reflects complex and variable histories of influenza infection and vaccination. The project investigates how past influenza exposure influences vaccine responses and effectiveness.
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.