Regulation Of Breast Cancer Metastasis By MiR-193b And MiR-342-3p
Funder
National Health and Medical Research Council
Funding Amount
$581,537.00
Summary
When breast cancer spreads to other organs, it results in high morbidity and mortality. MicroRNAs are a class of genes that control the expression of other genes, some of which are involved in the spread of cancer. In this project we will examine the function of two microRNA species that we have found to be associated with breast cancer spread. The anticipated outcome is a better knowledge of the genes that control cancer spread and the identification of new molecular targets for therapy.
TAF8 is a small protein that is associated with the general transcriptional apparatus. TAF8 is not an essential part of the general transcriptional machinery, but rather a regulatory molecule that appears to dictate how the machinery is used to express different genes. The absence of TAF8 leads to expression of genes controlling cell death. Since the avoidence of cell death is essential to the development of cancer these results will lead to a better understanding of how cancer develops.
Novel Role Of Innate Immune DNA Sensors In Promoting Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$774,025.00
Summary
Stomach cancer is the third most lethal cancer worldwide, and is strongly associated with inflammation (gastritis) caused by Helicobacter pylori bacterial infection. However it remains unknown how Helicobacter triggers gastritis and stomach cancer in people. Using a mouse model for gastritis-associated stomach cancer, our aim is to demonstrate the role of immune system proteins in the stomach which detect bacterial and host DNA to drive chronic inflammatory responses that lead to stomach cancer.
Individuals with stomach cancer, the second most lethal cancer world-wide, have a poor survival rate which is largely due to our poor understanding of the mechanisms which drive this deadly malignancy. Our aims are to identify how over-activation of a specific molecule of the immune system, called STAT3, in the mitochondria of cells promotes the growth of stomach tumours, and also examine whether blocking the actions of mitochondrial STAT3 can suppress the growth of gastric cancer cells.
Targeting PI3K-regulated Small Non-coding RNAs To Restore Cardiac Function
Funder
National Health and Medical Research Council
Funding Amount
$610,204.00
Summary
Heart failure affects approximately 2.4% of the adult population and over 11% of people over 80 years old. The majority of existing therapies slow, rather than reverse heart failure progression. The primary goal of this study is to determine whether regulating novel regulatory genes can enhance cardiac function in a setting of heart failure. Ultimately, technologies that target these genes may lead to innovative pharmacotherapies in the clinical management of heart failure.
Validating A Potential Therapeutic For Amyotrophic Lateral Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$614,254.00
Summary
ALS is a form of motor neuron disease that quickly renders people paralysed by killing off the nerves needed for muscle control. It affects people when they are 40-60 years old, and very few survive more than 5 years after diagnosis. Our team is testing a new therapeutic compound that we have already shown to delay paralysis in mice with ALS. The work we are currently undertaking will provide all the necessary information required before we are able to test our compound in people with ALS.
The Role Of Sirtuin (SIRT) Proteins In The Mechanisms That Regulate Infection Induced Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$516,430.00
Summary
Being born too early is the major cause of perinatal morbidity and mortality and accounts for the majority of neonatal deaths. The aim of this project is to gain a better understanding of the mechanisms involved in premature birth with a view to future development of clinically useful interventions to reduce the high rates of mortality and long-term disability.
6% of Australian men are infertile. Of these cases 50% are thought to be genetic in origin. Within this project we will replicate high-confidence genetic variants associated with human male infertility in the mouse. Doing so will allow the assignment of definitive genotype-phenotype correlations and the formulation of high confidence advice for clinicians and patients. It will also provide a means to define the mechanism of action and the tools for future pro-fertility treatments.
Determining The Role Of Parkin And PACRG In Protein Turnover
Funder
National Health and Medical Research Council
Funding Amount
$555,780.00
Summary
Alterations in the parkin gene are associated with neurodegenerative disorders such as Parkinson's disease (PD). The aim of this proposal is to characterise the function of parkin and the role it plays in disease development. We will determine the role of parkin in the brain and how loss of this function causes specific nerve cells to die. These studies will provide the means to develop novel therapeutic approaches to alleviate or prevent these disorders.
Deciphering Mechanisms Of Disease Evolution In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$845,093.00
Summary
In many patients, cancers are ever-changing, even after they have formed. This explains why many cancers can spread beyond the point of cure by surgery and why they can become resistant to treatments. This project will use patient melanomas and laboratory modelling to understand how melanomas change as they grow and spread. The results will be used to identify the nature of evolutionary changes in cancer in order to predict and even exploit them in treatment.