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Cells are building blocks of living things and require signalling pathways to communicate their functions. We discovered a new signalling pathway in flies that remarkably exists in yeast and plants to more complex organisms like mice and man. We will study this new signalling pathway in flies to find out how and why it communicates in cells. As flies and humans share similar genes, our studies will inform how this previously unknown signalling pathway functions from simple to complex organisms
Understanding How RUVBL1 And RUVBL2 Organise Chromosomes And Their Links To Disease
Funder
National Health and Medical Research Council
Funding Amount
$605,005.00
Summary
Our proposal will provide a deep mechanistic framework to inform both clinicians in diagnosis and management of RUVBL related diseases and also therapeutically, as industry looks to use these proteins as drug targets. The great excitement of RUVBL in translation has outpaced the gathering of vital knowledge underpinning the function; knowledge this proposal will provide for the first time.
Nedd4-2: A New Player In Polycystic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$671,995.00
Summary
Polycystic kidney disease (PKD) is a life threatening disorder affecting over 12 million people worldwide. This project is based on our discovery of a new gene that controls PKD. Using kidney specific gene knockout, biochemical and cellular approaches we will now address how this gene controls PKD. The results from this study will lead to better understanding of the underlying mechanisms that cause PKD, thus providing possible new targets for therapeutic interventions.
Cytotoxic lymphocytes are immune cells responsible for the killing infected or cancerous cells. How cytotoxic lymphocytes mature from a naive inactive to a fully activated state as they encounter infected or malignant cells is poorly understood, and will be investigated in the current proposal. Our results will aid in the development of novel therapies for cancer and other immunological diseases.
Pathogenic And Adaptive Molecular Interactions With Mutant Huntingtin Exon 1
Funder
National Health and Medical Research Council
Funding Amount
$727,117.00
Summary
This project aims to determine how the gene mutation that causes Huntington’s disease (HD) damages cells in the brain. The diseased gene creates a protein that is abnormally sticky, which causes it to form clumps. Our goal is to determine the components of the cell that are disrupted and damaged as clumping happens. Understanding this link will enable therapeutics to be logically designed in efforts to prevent harm to the brain, potentially before symptoms are evident.
The Hippo/Yap Pathway Reprograms Glucose Metabolism To Fuel Tissue Growth.
Funder
National Health and Medical Research Council
Funding Amount
$659,105.00
Summary
Liver disease is a common cause of sickness and death in Australia. While factors critical to liver function are known, the cellular networks responsible for causing liver cancer are largely undefined. Our studies will use zebrafish as a model to study how the circuit known as the Hippo pathway reprograms metabolism to promote liver cancer. These studies will enhance our understanding how metabolism regulates liver growth and identify therapeutic targets to combat liver cancer.
Role Of LncRNA IDH1-AS1 In Regulating C-Myc Driven-glycolysis And Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$685,043.00
Summary
It is thought that understanding cancer metabolism will reveal vulnerabilities that can be exploited in the clinic. Indeed, compared to most normal cells, cancer cells utilise different fuels to sustain proliferation and to adapt to their environment. Herein we have discovered a molecular switch that regulates the key metabolic enzyme IDH1 and show this controls tumour growth. Given this switch may be active in 50% of cancers we anticipate our work will have significance to many cancer types.
Tapping The Power Of Pluripotency: The Role Of HMGA1 In Stem Cell Self-renewal And Cell Fate Transitions
Funder
National Health and Medical Research Council
Funding Amount
$520,314.00
Summary
Stem-cell-based therapies have great potential as new treatments for degenerative and genetic diseases. However, to ensure we move in the right direction, we need a detailed understanding of stem cell properties. We have recently identified a novel mechanism for controlling stem-cell-like properties in both normal and cancer stem cells. In this project, we will further investigate this new means of controlling stem cells, which could revolutionise future therapeutic strategies for many diseases.
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.
Epigenetic Therapies To Differentiate And Eradicate Leukaemia Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$674,315.00
Summary
Leukemia stem cells (LSC) are often resistant to conventional and targeted therapies and therefore serve as the seed for leukaemia relapse. The overall aim of this project is to use small molecule therapies to block the activity of a particular protein (LSD1) in LSC in order to differentiate them and expose a vulnerability to another epigenetic therapy called a BET inhibitor. Together, these epigenetic therapies will differentiate and eradicate LSC, leading to improved outcome in AML.