Modelling TRPV4 Skeletal Disorders Using Human IPSCs
Funder
National Health and Medical Research Council
Funding Amount
$1,171,187.00
Summary
Inherited skeletal disorders are a significant disease burden. Many gene mutations have been defined but we only have limited understanding about how they cause the disease. We will use patient skin cells and new in vitro re-programing technology to induce them to form cartilage cells to produce “disease in a dish” models of human skeletal disorders. These models will allow us to answer questions about how specific mutations cause disease and identify potential therapies
Improving Muscular Dystrophy By Targeting The ADAMTS5 Metalloproteinase
Funder
National Health and Medical Research Council
Funding Amount
$658,571.00
Summary
Muscular dystrophy is a devastating childhood disorder. There is no cure and no effective therapy to stop the disease progressing to early death. Our pilot data show that muscular dystrophy in a mouse model is dramatically improved when the Adamts5 gene is inactivated. ADAMTS5 is an enzyme that remodels the extracellular matrix around cells. This suggests that inhibiting ADAMTS5 may be a new way to treat muscular dystrophy. We will test this idea in mice with muscular dystrophy
Development of Insulin-like peptide 5 (INSL5) peptide analogues as novel therapeutics. Insulin-like peptide 5 (INSL5) is a naturally-occurring hormone in the body that likely plays a role in the control of appetite. This project aims to develop new molecules based on INSL5 that could be suitable for use as drugs to treat various appetite-related disorders, such as obesity (where patients eat too much) or anorexia (where patients eat too little).
Structural And Functional Characterisation Of The Oncogene P-Rex1
Funder
National Health and Medical Research Council
Funding Amount
$623,447.00
Summary
The spread of cancer to other parts of the body (metastasis) is a major cause of mortality. The characterisation of proteins that regulate metastasis is therefore a priority. P-Rex1 plays a crucial role in promoting metastasis in breast and other cancers. We will determine the structural basis of P-Rex1 activity, and investigate how its dysregulation promotes aberrant cell growth. This study will provide the knowledge to build future drug development programs targeting P-Rex1 in cancer.
A microscopical examination of curdlan production by an Agrobacterium sp. We will investigate the secretion of the insoluble polysaccharide curdlan, a (1,3)-beta-glucan, from the surfaces of Agrobacterium cells and the assembly of the individual polysaccharide chains into microfibrils. Using state-of-the-art techniques in time lapse and electron microscopy we will compare the images of wild type curdlan-producing cells with those of mutants impaired in the production of curdlan. The outputs will ....A microscopical examination of curdlan production by an Agrobacterium sp. We will investigate the secretion of the insoluble polysaccharide curdlan, a (1,3)-beta-glucan, from the surfaces of Agrobacterium cells and the assembly of the individual polysaccharide chains into microfibrils. Using state-of-the-art techniques in time lapse and electron microscopy we will compare the images of wild type curdlan-producing cells with those of mutants impaired in the production of curdlan. The outputs will be information on the mechanics of curdlan production that will complement that emerging from our molecular biological and biochemical studies. These will have implications for understanding bacterial polysaccharide production in general and may have a commercial outcome in enhanced curdlan production.Read moreRead less
Regulation Of Neural Progenitor Cell Self-renewal By The RNA-binding Protein ZFP36L1 During Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$345,401.00
Summary
The timely differentiation of neural stem cells is critical during development, and the unrestrained proliferation of neural stem cells in the adult can lead to deadly brain cancers such as glioma. At present our understanding of the key molecules that regulate neural stem cell behaviour during these processes remains limited. In this proposal we will investigate the molecular determinants underpinning neural stem cell biology, both within the developing brain, and within glioma.
Solid phase synthesis of side-chain cross-linked peptide oligomers. This research will provide a unique opportunity to investigate the biological pathways and causative factors leading to diseases such as Alzheimer’s disease. Such information will guide the design and development of therapeutic strategies and diagnostic reagents.
Understanding HIV Resistance To Entry Inhibitors To Advance The Development Of Novel Antivirals
Funder
National Health and Medical Research Council
Funding Amount
$877,585.00
Summary
We cannot afford to be complacent in the search for improved anti HIV drugs for 2 principal reasons; First, worldwide a staggering 66% of infected individuals who need treatment are still unable to access therapy; and Second, the main reason why most treated patients are now living longer and more healthy lives is because we have never stopped developing newer therapies to provide options for patients. In this study we will develop and test newer drugs that block HIV infection of cells.