The Impact Of The Changes In Levels Of Adhesion Molecules NCAM2 And DsCAM On Synapse Formation And Function: Implications For Down Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$334,053.00
Summary
Down syndrome (DS) results from triplication of chromosome 21 and leads to mental retardation, molecular mechanisms of which are not understood. We found that two proteins, NCAM2 and DSCAM, encoded at chromosome 21 are highly expressed in synapses. Synapses are specialized contacts between neurons which allow neurons to process information in the brain. In this project we will test a hypothesis that changes in NCAM2 and DSCAM expression result in synapse abnormalities observed in DS.
Transplantation of pancreatic islets is the only cure for type 1 diabetes (T1D). Unfortunately, many of the transplanted islet cells die quickly due to an inadequate supply of blood. Herein, we investigate a novel cell surface protein for its role in islet and blood vessel survival and function. Furthermore, we use nanotechnology to provide said protein to the islet cells during transplantation for increased survival and function. Ultimately, this work may cure more patients with diabetes.
Regulation Of ICAM-1 Expression In Human Retinal Endothelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$565,967.00
Summary
Posterior uveitis is an inflammation that occurs within the eye and may result in blindness. Present treatments are not directed specifically at the inflamed tissues, and they may be ineffective and cause toxicity. This research aims to identify molecules controlling the entry into the eye from the bloodstream of the white blood cells that cause the disease. The results should suggest new targets for safer drugs to treat patients with posterior uveitis.
New Candidate Vaccines To Prevent Tuberculosis: Preclinical Assessment Of Efficacy, Safety And Mechanism Of Protection
Funder
National Health and Medical Research Council
Funding Amount
$594,133.00
Summary
Almost two million people die from tuberculosis (TB) each year. The curent vaccine, BCG, is ineffective at controlling TB and and the type of immune response needed to protect against the disease is poorly understood. We have discovered new antigens of the TB bacterium, and we will combine them with our innovative vaccine technology to develop new vaccines to control TB. We will also try and understand why BCG is not effective, and use this information to further improve TB vaccination.
Plasmodium vivax is a parasite that invades the youngest of human red blood cells. Our work will reveal how this malaria parasite enters our blood cells and the molecular mechanisms that allows successful invasion. This proposal will redefine our understanding of P. vivax invasion and explore novel ways to block its entry into red blood cells and therefore prevent malaria infection.
Mechanisms By Which Endothelial Selectins Regulate Normal And Malignant Stem Cell Fate
Funder
National Health and Medical Research Council
Funding Amount
$708,742.00
Summary
Hematopoietic stem and progenitor cells (HSPC) reside in the bone marrow (BM) and make all the cells of the blood system. We have found a molecule in the BM which when increased during inflammation, awakens normal HSPC. We previously showed this molecule also helps leukaemia and other cancer stem cells resist chemotherapy. We have now identified the mechanism why. These proposed studies open new therapeutic avenues to sensitise cancer stem cells to therapy enabling long-term cure.
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.
Group A streptococcus (GAS) is a bacteria that causes a wide range of disease in humans. GAS diseases are more common in Australias Indigenous population, and other health and economically disadvantaged groups than more affluent groups. In this study we will evaluate the effectiveness of novel vaccine candidates designed to prevent infection from all strains of GAS.
Prophylactic Vaccine Development For The Elimination Of Hepatitis C
Funder
National Health and Medical Research Council
Funding Amount
$936,752.00
Summary
A vaccine that prevents Hepatitis C is urgently needed to prevent infection and assist with global HCV elimination targets. This project grant will advance world-leading HCV vaccine candidates that generate both humoral and cellular immunity for clinical development.
Novel HIV-1 Glycoprotein Vaccines With Enhanced Presentation Of Broad Neutralization Epitopes
Funder
National Health and Medical Research Council
Funding Amount
$743,682.00
Summary
A prophylactic vaccine represents the best strategy for blocking HIV-1 transmission but one is not yet available. Current antiviral vaccines rely on neutralizing antibodies (NAbs) that block infection, however, current HIV-1 vaccine formulations do not induce broadly reactive NAbs (bNAbs). We have discovered a novel HIV-1 glycoprotein vaccination candidate with enhanced presentation of bNAb epitopes. We propose to determine if this vaccine induces effective bNAbs in experimental animals.