Targeting The Oncoprotein MDMX As A Novel Treatment For Triple Negative Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$561,672.00
Summary
Breast cancer (BrCa) is a leading cause of cancer death in women worldwide. BrCas unable to respond to current therapies have the worst outcomes. We propose a novel strategy to treat these cancers, based on our new findings. Our two protein targets are: (1) MDMX, that we found drives BrCa with its partner, (2) mutant p53, which causes cancer spread. We plan to directly target these drivers of aggressive BrCas, using new drugs that individually show great promise in trials in a number of cance
Splice Correction As A Treatment For Rare Diseases
Funder
National Health and Medical Research Council
Funding Amount
$824,316.00
Summary
We propose that a strategy of bringing effective and personalised treatments to amenable patients with rare genetic diseases, though ambitious, is readily achievable and opportune. Importantly, a consensus approach will facilitate expediting potentially curative treatments for many patients with rare diseases that would be unlikely to be commercially viable if considered individually.
Targeted Alternative Splicing: A Common Therapeutic Platform To Treat Inherited Diseases
Funder
National Health and Medical Research Council
Funding Amount
$797,165.00
Summary
Genes consist of exons (protein coding domains) separated by introns (non-coding intervening sequences). It is now evident that not every exon need be included in the gene message to direct synthesis of a functional gene product. This application seeks to identify which exons are essential for gene function and those exons that are "dispensable". Such information will allow personalized therapies to be developed based on splice switching, as we have done for Duchenne muscular dystrophy.
Blood-Brain Barrier Penetrating Antisense Therapy For Spinal Muscular Atrophy
Funder
National Health and Medical Research Council
Funding Amount
$635,005.00
Summary
Spinal muscular atrophy (SMA) is a genetic disease caused by the deficiency of a protein known as survival motor neuron.This results in the degeneration of motor neurons (nerve cells controlling muscles) leading to progressive muscle weakness, paralysis, and eventual death. Currently, there is no known cure for SMA. The aim of proposed research is to develop gene-modifying molecules that prevent degeneration of motor neuron and extend the life-span of mice as a potential therapy for SMA.
Optimization Of Splice Switching Therapies To Treat Duchenne Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$448,827.00
Summary
Duchenne muscular dystrophy, the most common and serious form of childhood muscle wasting, is caused by mutations in the dystrophin gene that block synthesis of the normal product. Antisense oligomers have been used in clinical trials to remove the disease-causing part of the message and rescue expression. Clinical trials have demonstrated proof-of-concept, although individual responses varied. This application seeks to improve the therapeutic potential of these compounds.
Molecular Characterization Of V-ATPase V0 Domain Subunits E1 And E2 In Osteoclast
Funder
National Health and Medical Research Council
Funding Amount
$558,909.00
Summary
Osteoporotic fractures in the elderly are often linked to increased mortality rates. Excess bone resorption is a major contributor to the onset of the disease. The proposed project focuses on the investigation of the molecular mechanisms of acid secretion that is required for the bone degradation in body. The project will examine the role of the proton pump in bone resorption and seek potential targets for the treatment of osteoporosis.
Epigenetic Regulation Of L1 Retrotransposition In Mouse Models Of Abnormal Human Neurobiology
Funder
National Health and Medical Research Council
Funding Amount
$417,812.00
Summary
Retrotransposons are mobile genes that copy-and-paste themselves to spread in DNA. Until very recently, they were thought to only be active in sperm and egg. In our recent work, we demonstrated that they also move in the brain. In the current study, we will use cutting-edge technologies to determine how retrotransposons change the genetic makeup of neurons in neurodevelopmentally impaired mice to predict whether these mutations would also be present in human brain disorders.
Deciphering The Overlapping Roles Of SSB1 And SSB2 In The Regulation Of Haematopoiesis And Intestinal Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$996,631.00
Summary
Our work centres on elucidating the role of two newly identified and related single-stranded DNA binding protein (Ssb1 and Ssb2) in development of blood and gut system. When both genes are deleted mice die with 8 days of knockdown due to bone marrow failure and intestinal atrophy. Our double knockout model parallels the consequences of radiation damage on blood and gut system. Toxicity to these systems is a significant hindrance in delivering anti-tumor therapy.
Problems in learning, memory and other complex mental processes are common to many brain disorders. This project will study the impact of mutations on a family of genes reported in autism and schizophrenia, on complex cognitive behaviours using novel behavioural technologies. This will not only shed fundamental insights into the specific mental processes regulated by these genes and their role in disease, but importantly provide novel targets for the development of therapies.
Vitamin D Synthesis Within Osteoblasts Increases Bone Mineral By Regulating Remodelling: Is This The Link Between Vitamin D Status And Fractures?
Funder
National Health and Medical Research Council
Funding Amount
$627,082.00
Summary
This project will contribute to understanding mechanism of vitamin D action within bone to modulate bone resorption and offers the exciting prospect of identifying the mechanism by which an adequate vitamin D status can reduce the risk of osteoporotic hip fractures. Thus, this project has great potential to improve community health by being able to recommend vitamin D supplementation made on the basis of maintaining normal bone cell function with psarticular reference to modulating bone resorpti ....This project will contribute to understanding mechanism of vitamin D action within bone to modulate bone resorption and offers the exciting prospect of identifying the mechanism by which an adequate vitamin D status can reduce the risk of osteoporotic hip fractures. Thus, this project has great potential to improve community health by being able to recommend vitamin D supplementation made on the basis of maintaining normal bone cell function with psarticular reference to modulating bone resorption.Read moreRead less