Pre-clinical Assessment Of The Therapeutic Potential Of Targeting The Hippo Pathway In Muscle Wasting & Muscle-derived Cancer
Funder
National Health and Medical Research Council
Funding Amount
$621,979.00
Summary
Recent findings have identified the Hippo signalling pathway as an important regulator of processes in muscle fibres and muscle progenitor cells. This project will look at the significance of the Hippo pathway in the development of muscle wasting caused by statin administration, and in the genesis of muscle derived tumors (rhabdomyosarcoma). The studies will determine if interventions that regulate the Hippo pathway could provide new therapies for these important muscle-related diseases.
Fzd receptors are often upregulated in gastric cancer, and recent studies have shown that targeting these receptors has be effective at reducing cancer cell growth in other cancers including prostate and breast. This project will use cutting edge technology to firstly determine the specific requirement for Fzd receptors during gastric cancer and then determine the therapeutic benefit of using an antibody to target these receptors in mouse models and human gastric cancer cells.
Suppressor Of Cytokine Signalling (SOCS4) Is A Critical Regulator Of The Anti-viral Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$616,912.00
Summary
The SOCS proteins are negative regulators of cytokine signalling and immune cell development and function. SOCS4 is the last remaining SOCS protein for which there is no described function or intracellular target. We intend to use well-defined acute and chronic viral disease models, and investigate the role of SOCS4 in infection in order to unravel its function. We will also search for its binding partners and intracellular targets, and determine the signalling pathways regulated by SOCS4.
Glioblastomas are the most common and lethal brain tumours and 5 years after diagnosis only 20% of patients diagnosed with a glioblastoma will be alive. The poor survival rate is due to the ability of these tumours to extensively penetrate into the surrounding healthy brain tissue making complete surgical removal very difficult. Our research aims to discover how the glioblastoma cells can penetrate neighbouring brain tissue.
Alpha-actinin-4 As An Oncogenic Driver And Therapeutic Target In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$401,786.00
Summary
Despite the recent advances in targeted therapy and immunotherapy, curative treatment of metastatic melanoma remains an unmet health problem. In this project, we will potentially demonstrate that a protein called ACTN4 is abnormally expressed at high levels in melanoma cells and plays an important role for melanoma cell survival and resistance to treatment, and thus identify inhibition of ACTN4, either alone or in combination with other drugs, as a novel approach in the treatment of melanoma.
The Role Of Store-operated Calcium Entry In Neuronal Development
Funder
National Health and Medical Research Council
Funding Amount
$353,140.00
Summary
Defects in brain development can manifest in a range of disorders including autism and mental retardation. The highly complex, precise network that is our nervous system forms during development. Our work will determine the role of key proteins in guiding developing neurons. Understanding the function of such proteins will improve our ability to predict the outcome caused by mutations in these proteins, in the developing foetus.
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.
Investigating The Roles Of The Wnt And Notch Signalling Systems In Colon Cancer Crypt Biology
Funder
National Health and Medical Research Council
Funding Amount
$604,439.00
Summary
Colon cancer occurs because of mutations to a tumour suppressor gene. These mutations alter the growth and positional signals for the cancer cells. This project aims to produce a computer model of the regulatory processes in normal colonic cells, to discover why the mutations lead to cancer and to discover rational drug targets for interfering with the growth of colon cancer cells.
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.
Investigating The Cellular Response To Iron-Depletion: The Trilogy Of ASK1, Thioredoxin And Ribonucleotide Reductase
Funder
National Health and Medical Research Council
Funding Amount
$552,572.00
Summary
Iron is crucial for many essential biological processes. Recently, we demonstrated that iron-depletion can affects important signalling pathways (e.g., JNK and p38) that play important roles in growth arrest and apoptosis. This study is designed to investigate the cellular and molecular effects of iron depletion which currently remains unclear. The research is crucial for understanding: (1) the effects of iron deficiency and (2) for understanding the effects of iron chelators that are used for t ....Iron is crucial for many essential biological processes. Recently, we demonstrated that iron-depletion can affects important signalling pathways (e.g., JNK and p38) that play important roles in growth arrest and apoptosis. This study is designed to investigate the cellular and molecular effects of iron depletion which currently remains unclear. The research is crucial for understanding: (1) the effects of iron deficiency and (2) for understanding the effects of iron chelators that are used for treating various diseases.Read moreRead less