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Deciphering The Function Of Caspase-2 In DNA Damage Response And Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$808,007.00
Summary
Aberrant cell death and DNA damage response (DDR) are hallmarks of tumourigenesis. Recently we have discovered that an enzyme, caspase-2, previously implicated in cell death execution, also works in DDR and acts as a tumour suppressor. We now wish to validate these finding in preclinical models of cancer and understand precisely how caspase-2 safeguards against cancer development. These studies will help better understand tumourigenesis and may lead to the discovery of new drug targets.
Autophagy And Growth Signalling In Developmentally Programmed Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$594,133.00
Summary
Cell death is essential for normal development and deregulated cell death results in many diseases. We have recently discovered a potentially novel mechanism of developmental cell death that involves autophagy (a type of self-degradation). Our studies will now examine the mechanism of autophagic cell death and study how cell growth regulation is integrated in this pathway. This will provide us important knowledge into the complex role of autophagy in cancer.
Controlling The Pro-survival Protein Mcl-1: Discovering Novel Opportunities And Developing Innovative Approaches To Target Mcl-1 For Treating Cancers
Funder
National Health and Medical Research Council
Funding Amount
$749,415.00
Summary
Cancer cells are often sustained by evading cell death. Thus, a promising approach to develop new cancer treatments aims to restore their ability to commit cell suicide. Proteins related to Bcl-2 are, in this regard, attractive targets because they are prominent barriers to cell death. This project seeks to uncover how a Bcl-2 relative, Mcl-1, is regulated, and to explore how the mechanisms that underpin these processes can be targeted in cancers (melanomas, leukemias) that it sustains.
Investigating The Role Of SERPINB6 In Cochlear Function And Deafness
Funder
National Health and Medical Research Council
Funding Amount
$570,803.00
Summary
In 2010 a novel genetic mutation was identified that causes progressive hearing loss in humans, however, it was not established why this mutation leads to the disease. We propose that the mutation renders cells of the inner ear more susceptible to death caused by noise trauma. We will investigate this in a mouse model of the human condition. This could lead to the development of therapies that prevent hearing loss.
Understanding The Regulation Of Kidney Morphogenesis In Order To Improve Renal Development
Funder
National Health and Medical Research Council
Funding Amount
$683,040.00
Summary
Chronic kidney disease is a growing burden to the health system. The long term health of your kidneys is influenced by the number of functional units, nephrons, present in each kidney, a feature that is determined before birth. If we could influence this number, we may be able to reduce the risk of kidney disease in later life for at risk populations, including the Aboriginal community. This study will investigate the stem cells that form the nephrons, how the process occurs and how it can be in ....Chronic kidney disease is a growing burden to the health system. The long term health of your kidneys is influenced by the number of functional units, nephrons, present in each kidney, a feature that is determined before birth. If we could influence this number, we may be able to reduce the risk of kidney disease in later life for at risk populations, including the Aboriginal community. This study will investigate the stem cells that form the nephrons, how the process occurs and how it can be influenced.Read moreRead less
Characterisation Of Two New Kinases In The Hippo Tumour Suppressor Pathway
Funder
National Health and Medical Research Council
Funding Amount
$550,602.00
Summary
The Hippo pathway is a key regulator of tissue growth. It was first discovered in vinegar flies and plays a similar role in mammals. We aim to define the mechanism by which the Gish and Fray kinases control tissue growth by regulating the Hippo pathway. These studies will be performed in flies and mammalian cell culture. Our studies will shed light on how tissue growth is controlled, and have the potential to inform the way that we treat human cancers and tissue growth disorders.
Defining The Molecular Regulators Of Apoptotic Cell Disassembly And Their Role In Cell Clearance And Lupus-like Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$773,848.00
Summary
In humans, billions of cells will die daily as part of normal turnover in various organs. It is vital that dying cells are rapidly removed as their accumulation has been linked to autoimmunity and inflammation. To aid efficient removal of dead cells, dying cells can disassemble into smaller fragments for neighbouring cells to engulf. We aim to understand the machinery that controls how dying cells can disassemble into smaller pieces and their function in cell clearance and autoimmunity.
The Hippo pathway is a key regulator of tissue growth. It was first discovered in vinegar flies and plays a similar role in mammals. We aim to define the mechanism by which the different transcription factors in the Hippo pathway operate to control tissue growth. These studies will be performed in flies and mammalian cell culture. Our studies will shed light on how tissue growth is controlled, and have the potential to inform the way that we treat human cancers and tissue growth disorders.
ARC, A Newly Identified Regulator Of Chondrocyte Differentiation And Death, Is A Novel Therapeutic Target For OA
Funder
National Health and Medical Research Council
Funding Amount
$763,983.00
Summary
We have identified a critical regulator of the survival and normal metabolism of the cells in articular cartilage. Loss of this molecule is an early event in joint injury that leads to osteoarthritis (OA). The current proposal will determine the mechanisms whereby this protein functions to protect cartilage breakdown in OA, how its levels in chondrocytes are regulated in both healthy and diseased conditions, and at what stages of disease increasing its expression protects against OA progression.
Killing Infected Cells As A Mechanism To Eradicate Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$1,085,770.00
Summary
Mycobacterium tuberculosis (Mtb), the causative agent of TB, is rapidly becoming resistant to all antibiotics and this disease kills more than one million people each year. This underscores the urgent need to develop new treatments for this disease. We are developing a therapy that kills Mtb infected cells and may help to eradicate infection. This highly novel approach to the treatment of TB would have profound implications for the 2 billion people infected with this pathogen.