The Role Of Host Proteases In Modulating Enteric Infectious Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,267,155.00
Summary
Bacterial pathogens that cause gut diseases result in 2.5 million deaths per year. The gut is a complex environment consisting of numerous factors that must be balanced to maintain enteric health. When these factors are unbalanced, disease can occur, and infections can cause imbalances. This project will increase our understanding of the role that host proteins play in gut infections, providing knowledge critical for developing improved strategies for disease treatment and prevention.
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.
Virulence Associated Small RNAs In Acinetobacter Baumannii
Funder
National Health and Medical Research Council
Funding Amount
$964,148.00
Summary
This proposal aims to understand how a superbug that causes severe infections in hospitalised patients worldwide and is known to be resistant to almost all available antibiotics, causes disease. We then plan on using this information to guide the development of a new type of therapy to treat this severe infection.
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.
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.
Antibiotic Conjugates: Joining Together To Fight Antimicrobial Resistance
Funder
National Health and Medical Research Council
Funding Amount
$697,675.00
Summary
New strategies are urgently needed to treat the rise of infections from multidrug-resistant bacteria, with standard antibiotic therapies becoming obsolete. This project will develop multiple innovative approaches to overcome antibiotic resistance, based on a core concept of appending additional functionality to existing antibiotic scaffolds. New conjugates will be synthesized, tested for antimicrobial activity, then optimized via a validated antimicrobial development pipeline.
How A Multidrug Resistant Bacterial Pathogen Has Become Pandemic
Funder
National Health and Medical Research Council
Funding Amount
$1,116,544.00
Summary
The pandemic spread of antibiotic resistant E. coli ST131 is a major human health problem. ST131 is the globally dominant cause of urinary tract and bloodstream infections. This project will use advanced genetics and animal infection models to understand the features of ST131 that have fueled its global dominance. The outcomes will unravel the molecular mechanisms that enable ST131 to persist and cause repeat infection, and guide the development of new precision medicine therapeutics.
Developing New Immunotherapeutics Through Studying Immune Effectors In Situ
Funder
National Health and Medical Research Council
Funding Amount
$1,369,054.00
Summary
The immune system deploys pore forming proteins to clear viral and bacterial infections and to eliminate cancerous cells. The unwanted activities of these molecules, however, results in chronic disease and in transplant rejection. We aim to understand how pore forming immune weapons interact with our own cells, with the goal of using this information to develop new approaches to treat immune driven disease and to improve the success of transplantation therapy.
Should You Be Eating That? Food-derived Bacteria And Their Role In Treating Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,405,182.00
Summary
The clinical application of medicines based on the microbes that exist as part of microbiomes is now a reality. Despite these rapid advances understanding how the bacteria are transmitted and recolonise after disruption is essential. Our preliminary data suggests that the average Australian adult consumes over 10 million bacteria per day in their diet. This project seeks to understand these relationships and how they can be exploited to develop the next generations of microbiome based medicine.
Novel Antibiotics That Harness Innate Immunity To Overcome Multi-drug Resistant S. Aureus
Funder
National Health and Medical Research Council
Funding Amount
$872,355.00
Summary
Controlling infection with antibiotics is essential in medicine. However, bacterial resistance to antibiotics is growing rapidly. Here, we propose new strategies to treat multi-drug resistant Staphylococcus aureus by combining existing clinical antibiotics with either a targetted immune response or by removing the ability of bacteria to hide from our immune system. These novel approaches will allow us to overcome infections caused by resistant bacteria, which are a serious and growing problem.