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.
Cryo-EM Inspired Drug Discovery To Treat Human Fungal Pathogenic Infections
Funder
National Health and Medical Research Council
Funding Amount
$987,505.00
Summary
Invasive fungal infections are a major threat to global human health. These are highly prevalent in patients whose immune system is compromised (e.g. HIV, cancer or organ transplant patients). Of growing concern is the rise of new strains of fungal infections that are resistant to at least one of the four drug families being used to treat these infections. Here, we will create new therapeutics that block the activity of an enzyme whose activity is essential for the survival of these pathogens.
Structure And Mechanism Of Activation Of The Mechanosensitive Ion Channel TACAN
Funder
National Health and Medical Research Council
Funding Amount
$997,537.00
Summary
We propose to determine the structure and mechanism of activation of TACAN, a recently identified ion channel that defines a novel and uncharacterised class of channels. TACAN is specifically involved in sensing mechanical pain and contributes to mechanosensitive currents in the pain-receptor type of neurons. Our studies will increase knowledge of this novel class of proteins that will allow for the future development of treatments for several chronic pain conditions including arthritis.
Using Immunological Principles To Inform Malaria Vaccine Design
Funder
National Health and Medical Research Council
Funding Amount
$577,763.00
Summary
Malaria kills ~420,000 people each year worldwide. While a vaccine does exist, efficacy is poor and protection wanes rapidly. We have made breakthroughs in understanding the immune response to malaria that allow us to design a new generation of malaria vaccines. Based on this we aim to generate a vaccine that induces sustained levels of high-quality antibodies targeting multiple targets on the parasite and so can provide sustained long-term protection.
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.
Integrating Biology And Medicine To Develop 3D-structure Guided Drug Design For Treatment Of Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$978,832.00
Summary
Calcium channel inhibitors are commonly prescribed for the treatment of heart disorders such as angina, hypertension, arrhythmias and hypertrophic heart disease. This class of drugs is one of the leading causes of drug-related fatalities. The impediment to designing better drugs is a lack of understanding of the 3 dimensional (3D) structure of the calcium channel. We will enable for the first time a 3D structure blueprint for the design of safe and highly selective calcium channel therapeutics.
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.