A Nanomedicine Strategy For Detecting And Modulating Protease Activity In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$455,534.00
Summary
Protease enzymes are vitally important for normal bodily function but can play a deleterious role in many diseases such as cancer, aging diseases and eye diseases. The proposed research will provide a nanomedicine solution to the detection and therapeutic control of protease activity in vivo using nanoporous optical devices that are benign to the body. This general strategy for will be demonstrated in eyes with a view to detection and treating the eye disease uveitis.
Molecular Basis For The Efficient Processing Of Antigens Taken Up By Clec9A, A DAMP Receptor On Dendritic Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,302,392.00
Summary
Dendritic cells (DC) of the immune system utilise specific receptors to sense danger signals from their environment. We identified a DC danger receptor, Clec9A, which recognizes and induces immunity to “dangerous” dead cells eg. infected cells or killed tumour cells. We will investigate how DC use Clec9A to process “dangerous” dead cells, and the factors that control the potency of this immune response. This will enable us to develop novel immunotherapies for infectious diseases and cancer.
Enhancing Vaccine Efficacy By Harnessing Dendritic Cell Receptors And Their Unique Properties
Funder
National Health and Medical Research Council
Funding Amount
$687,519.00
Summary
Potent vaccination might be achieved by using monoclonal antibodies as magic bullets to target vaccines to special cells in the body. We show that targeting these special cells by using monoclonal antibodies that recognise Clec9A is effective, perhaps because it brings several different immune cells together so that they orchestrate very efficient immune responses. This application investigates how targeting Clec9A allows strong vaccination so that we can apply this to new generation vaccines.
The Regulatory Role Of Clec12A In Antigen Presentation And Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,381,077.00
Summary
The immune system maintains a balance between initiating immune responses to infections and suppressing immune responses in health. We have identified, on the surface of specialised immune cells, a protein that is critical for regulating immune responses and dampening down inflammation. This proposal aims to determine how this protein functions in health and under inflammatory conditions, and to develop approaches based on its molecular interactions to reduce inflammatory disease.
Improving Synthetic Methodology To Prepare Pre-clinical Analogues Of Human Insulin
Funder
National Health and Medical Research Council
Funding Amount
$457,708.00
Summary
The glucose regulatory hormone, insulin, remains the only treatment for type I diabetes and up to 30% of type II diabetes, both of which are among the world’s fastest growing chronic diseases today. Because insulin, if taken orally, would be broken down quickly, it has usually been given by injection. This project will develop novel chemical methods for the efficient preparation of novel insulin therapeutics with improved stability and oral bioavailability for prolonged treatment of patients.
Var Gene Diversity And Naturally Acquired Immunity To Malaria
Funder
National Health and Medical Research Council
Funding Amount
$410,664.00
Summary
In areas where malaria is common, people develop natural immunity to the disease albeit very slowly due to the many parasite strains that circulate. The project will use protein microarrays to investigate the patterns by which antibodies are acquired to the majority of strains. This will reveal how antibodies are acquired with age and which are associated with protection against malaria symptoms. The research aims to identify biomarkers of malaria immunity and may lead to new vaccine candidates.
Improving the function of GABA-A receptors is a key property of several classes of clinically important drugs including benzodiazepines and many anticonvulsants. However, the binding sites and molecular mechanisms of these drugs remain poorly understood. Using compounds similar to those in green tea, we will determine the molecular mechanism of these drugs. This understanding will lead to the development of better drugs for treatment of anxiety, depression, epilepsy, insomnia & schizophrenia.
Molecular Characterisation Of The Dendritic Cell Receptor Clec9a And Its Ligand Interactions
Funder
National Health and Medical Research Council
Funding Amount
$651,784.00
Summary
The immune system senses danger from infectious diseases, damaged and dead cells. We identified a danger receptor, Clec9A, on a specialised cell type of the immune system in mice and humans. Clec9A recognizes and induces immunity to dangerous dead cells. Delivering vaccines to Clec9A improves vaccine responses. We will investigate how Clec9A recognises and reacts to danger, and how we can mimic this recognition to improve vaccine design.
Development Of Selective Melanocortin Receptor Agonists And Antagonists
Funder
National Health and Medical Research Council
Funding Amount
$684,607.00
Summary
Human melanocortin receptors play a key role in a variety of physiological processes ranging from energy regulation, skin pigmentation and regulation of food intake. This project aims to generate novel peptide based molecules that will selectively interact with different melanocortin receptors to better understand their pharmacology thereby opening the potential for future drug development for obesity, stroke or inflammatory skin disorders.
The WHO estimates there were ~189 million clinical cases & 584,000 malaria-related deaths in 2013. This translates to ~1,600 child deaths daily. There is no licensed malaria vaccine & all available drugs are associated with resistant parasites. This enormous health issue is driving the search for new therapies. We address this issue by identifying new drug candidates for malaria prevention, with unique modes of action to treatment drugs in order to overcome issues of parasite drug resistance.