Host-directed Therapy For Malaria: Host Cell Signalome As A Target
Funder
National Health and Medical Research Council
Funding Amount
$898,043.00
Summary
Malaria parasites kill 450,000 children a year and impact on the economic development of communities. Spreading drug resistant malaria parasites within Australia's South-East Asian neighbours creates an urgent and unmet need for new drug treatments. We will characterise host signals required for parasite survival in immature erythrocytes and identify host-directed, ready to develop, resistance-proofed drugs to kill malaria parasites.
Identifying The Correlates Of Protective Immunity Against Invasive Staphylococcus Aureus Infection
Funder
National Health and Medical Research Council
Funding Amount
$954,131.00
Summary
The bacteria Staphylococcus aureus (S. aureus) remains a major cause of human infections, and the rise of highly pathogenic, antibiotic-resistant strains is making treatment increasingly difficult. In this project we will examine the immune response to S.aureus to determine which parts of the immune system are involved in responding to the bacteria. This knowledge will lay the foundation for which new innovative S. aureus vaccines will ultimately emerge.
Plasmodium falciparum is the most lethal malaria parasite that infect humans. Our work will reveal how this malaria parasite governs host tropism, fertilization and immune evasion by using the 6-cysteine family of proteins which are abundantly expressed on its surface. This proposal will explore novel ways using the smallest types of antibodies, called nanobodies, to block the function of these proteins and therefore prevent malaria infection.
Structure And Biophysical Analysis Aided Design Of Novel Toxoid Vaccines For A Major Class Of Bacterial Toxins.
Funder
National Health and Medical Research Council
Funding Amount
$608,425.00
Summary
Inactivated bacterial toxins (toxoids), such as the tetanus vaccine, are safe and effective vaccines. Cholesterol dependent cytolysins (CDCs) are bacterial toxins produced by many important human pathogens including Group A Streptococcus (GAS) and Pneumococcus. GAS has no available vaccine and Pneumococcus does not have a universal vaccine. We have developed a new way of inactivating CDCs based on new knowledge of how they target human cells and will use this knowledge to make new vaccines.
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.
Targeting Pathogenic TAR DNA-binding Protein 43 To Treat Frontotemporal Dementia And Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$687,444.00
Summary
Frontotemporal dementia and motor neuron Disease are rapidly progressive and fatal neurodegenerative diseases that affect people in their prime. Poor understanding of the processes that lead to these diseases have slowed drug development. Through innovative experimental design, we aim to decipher a novel disease mechanism that involves specific molecular interactions and translate these findings into new therapies for the diseases.
Flaviviruses Must Come Of Age: Design Of Stable, Mature Particles By Structural Vaccinology
Funder
National Health and Medical Research Council
Funding Amount
$1,149,487.00
Summary
We have established a powerful toolset combining advanced structural biology and rapid virus engineering that allows us investigate the assembly of flaviviruses in novel ways. This project will integrate these approaches to investigate the role of new ligands that we have identified in the structure of medically-relevant flaviviruses including dengue virus and delineate a novel maturation path for flaviviruses, which will be used to design safer and more effective flavivirus vaccines.
Targeting MiRNA Biogenesis To Treat Herpes Simplex Virus Latency
Funder
National Health and Medical Research Council
Funding Amount
$800,085.00
Summary
Herpes simplex virus (HSV) causes cold sores in most infected people, but can also cause blindness and fatal brain infections. The biggest problem with HSV is that it never completely goes away - the virus hides in a part of the nervous system and can come out to cause disease over and over again. We have recently discovered a gene in people that the virus needs to maintain itself in this hidden state. In this project we will use this exciting discovery to work towards a cure for HSV.
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.
Development Of An Intracellular Tau-specific Antibody Therapeutic For The Treatment Of Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$410,378.00
Summary
The protein, tau, is a promising therapeutic target for the treatment of Alzheimer's disease and related dementia's. Targeting tau is a challenge, however, as it is mostly localised within brain cells and a therapeutic must therefore be able to cross multiple barriers to engage and neutralise tau. This project overcomes this hurdle by using virus' to deliver a tau-specific antibody gene across the multiple barriers where it can be produced by brain cells and target intracellular tau.