Nanoparticle And Virus Assisted Targeting Of MicroRNA And DNA For The Treatment Of Atherosclerosis, Myocardial Infarction And Other Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$663,583.00
Summary
Inflammation is an underling cause or aggravating factor of many diseases, such as heart attack and atherosclerosis, but there is a lack of effective anti-inflammatory drugs that do not cause side effects. Using advanced biotechnology, we will use viruses and nanoparticles to selectively target gene therapeutics to areas of inflammation, resulting in high efficacy with low side effects. We will test these broadly usable therapeutics in mouse models of heart attack and atherosclerosis.
BRCA-P: An International Randomised Phase III Study Evaluating The RANK Ligand Inhibitor Denosumab For The Prevention Of Breast Cancer In BRCA1 Mutation Carriers
Funder
National Health and Medical Research Council
Funding Amount
$2,589,049.00
Summary
Women with a faulty BRCA1 gene are at high lifetime risk for breast cancer. Identifying a safe and effective prevention therapy is therefore a ‘holy grail’. We have discovered that denosumab, used to treat osteoporosis or breast cancer spread to bone, could be ‘repurposed’ as a prevention drug. BRCA-P is an international randomised controlled study that will determine if denosumab prevents breast cancer. Associated translational research will facilitate swift transfer to the clinic.
Dystrophin Gene Repair In Mdx Mouse Myoblasts And Bone Marrow Cells As A Basis For Autologous Transplant In Human DMD
Funder
National Health and Medical Research Council
Funding Amount
$422,036.00
Summary
The muscular dystrophies are inherited diseases that lead to muscle wastage and severe disabilities. The most severe forms result in the early death of newborns, but a large number are diagnosed in children showing early mild symptoms and progress steadily to severe disabling forms in the juvenile and young adult. Perhaps the most devastating of these dystrophies is Duchenne Muscular Dystrophy (DMD). This condition affects 1 in 3,300 boys, who show symptoms at around 5 years of age until wheelch ....The muscular dystrophies are inherited diseases that lead to muscle wastage and severe disabilities. The most severe forms result in the early death of newborns, but a large number are diagnosed in children showing early mild symptoms and progress steadily to severe disabling forms in the juvenile and young adult. Perhaps the most devastating of these dystrophies is Duchenne Muscular Dystrophy (DMD). This condition affects 1 in 3,300 boys, who show symptoms at around 5 years of age until wheelchair confinement by early teens. DMD boys undergo major clinical and surgical treatments which at present only provide small but significant improvements to their lives. The median age at death for Duchenne boys is 22 years. The cause of DMD has been known for almost 2 decades and is a defect in just a single component of muscle, Dystrophin which is produced by muscle cells. In general, boys with DMD possess Dystrophin which is missing an important part that prevents the breakdown of muscles during activity. As a consequence, all the muscles in DMD boys slowly break down over their lifetime until they die because the muscle which helps in drawing breath (Diaphragm) is no longer capable of helping them to breathe. The muscle component Dystrophin is produced by a gene (the dys gene) and the defect of Dystrophin is caused by a defect in the dys gene. If the dys gene defect was able to be corrected in boys with DMD, their Dystrophin may also be corrected and the breakdown of their muscle prevented. We have been able to correct the dys gene in muscle cells from a mouse with DMD. We wish to improve this technology and allow muscle to be repopulated with genetically corrected cells to form a basis for treatment of human DMD. In this way we hope to significantly improve and lengthen these boys' lives and even lead to a cure for DMD and other genetic muscle diseases.Read moreRead less
A Systems Biology Approach To Defining Therapeutic Targets In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$633,112.00
Summary
Breast cancer is a very complex disease affecting large numbers of women. Current treatment strategies are effective at controlling the disease for patients, however many continue to be burdened by their disease as their tumour either does not respond or develops resistance to the treatment. We will use mathematical approaches to analyse large and complex data sets generated from breast cancers to identify new therapeutic targets and improve patient outcomes.
Malaria is a very important disease worldwide, causing hundreds of millions of cases and about two million deaths per year. Severe malaria including cerebral malaria is a major cause of death. It is caused by red blood cells which contain malaria parasites sticking to the lining of microscopic veins and clogging them; what happens after this is complex. The process of sticking is called cytoadherence. We have discovered a gene which is important in this process of sticking. We have called it by ....Malaria is a very important disease worldwide, causing hundreds of millions of cases and about two million deaths per year. Severe malaria including cerebral malaria is a major cause of death. It is caused by red blood cells which contain malaria parasites sticking to the lining of microscopic veins and clogging them; what happens after this is complex. The process of sticking is called cytoadherence. We have discovered a gene which is important in this process of sticking. We have called it by the acronym clag, for cytoadherence-linked asexual gene; most Australians know of Clag as a glue. Our evidence for this has been accepted for publication by the prestigious USA journal Proceedings of the National Academy of Sciences of the USA. Recent work overseas aimed at determining the entire DNA sequence of the malaria parasite has shown that clag is not alone; there are at least 9 slightly different clag genes in the malaria parasite. What do the others do? We propose two possibilities. The first is that all of them act in cytoadherence but that different clags enable the parasitised cells to stick to different things on the lining of veins. The second is that they enable the parasitised cells, or perhaps the parasites alone, to stick to other things at different stages of the complex life cycle of the parasite. The experiments that we propose should show whether either of these proposals is true.Read moreRead less
Identification Of Cancer Initiating Cells In Small-cell Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$364,420.00
Summary
Lung cancer is the leading cause of cancer deaths worldwide. Recently a unique mouse model of small-cell lung cancer (SCLC) has been generated that closely mimics the human disease. We will use this model to identify the cells that give rise to SCLC upon genetic alteration. Results obtained will assist in designing more effective intervention strategies aimed at overcoming initial and acquired resistance of these tumours against cytotoxic and targeted drugs.
Understanding Sensitivity And Resistance To Trastuzumab And Lapatinib In HER2 Overexpressing Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$414,056.00
Summary
Previously, women diagnosed with a breast cancer that overexpressed the HER2 protein had a very high risk of dying. Trastuzumab, a treatment targeted at this protein, has been an extremely effective treatment. Currently there are new anti-HER2 drugs available, which will likely to be used in combination with trastuzumab. We will be investigating biological markers of resistance and sensitivity to these drugs and combinations in order to try and understand who needs which drug and/ or combination ....Previously, women diagnosed with a breast cancer that overexpressed the HER2 protein had a very high risk of dying. Trastuzumab, a treatment targeted at this protein, has been an extremely effective treatment. Currently there are new anti-HER2 drugs available, which will likely to be used in combination with trastuzumab. We will be investigating biological markers of resistance and sensitivity to these drugs and combinations in order to try and understand who needs which drug and/ or combinations.Read moreRead less
Antibody Targeted Virus Particles For A Gene Therapy Approach To Inhibiting Atheroschlerosis Development
Funder
National Health and Medical Research Council
Funding Amount
$95,313.00
Summary
I am a Biotechnologist and my research looks into ways of preventing Atherosclerosis. Atherosclerosis is the build up of plaques in artery walls, and is the major precursor condition to stroke and myocardial infarction (heart attack). My project focuses on a preventative gene therapy which will be delivered specifically to early stage plaques. The gene will inhibit one of the earliest developmental stages of atherosclerosis: recruitment of immune cells to these sites, and so prevent their growth ....I am a Biotechnologist and my research looks into ways of preventing Atherosclerosis. Atherosclerosis is the build up of plaques in artery walls, and is the major precursor condition to stroke and myocardial infarction (heart attack). My project focuses on a preventative gene therapy which will be delivered specifically to early stage plaques. The gene will inhibit one of the earliest developmental stages of atherosclerosis: recruitment of immune cells to these sites, and so prevent their growth.Read moreRead less
Targeting Critical Nodes On The IGF1-PI3K Pathway To Improve Function Of The Failing Heart
Funder
National Health and Medical Research Council
Funding Amount
$512,947.00
Summary
Heart failure is a major clinical problem which is becoming worse as our population grows older and comorbidities such as obesity and diabetes become more prevalent. Current heart failure therapeutics largely delay disease progression. This research proposal focuses on strategies designed to improve function of the failing heart, as opposed to simply delaying disease progression. This approach will lead to the development of new therapeutics.