Probing Changes In G Protein-coupled Receptor Signalling Networks During Breast Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$892,733.00
Summary
The b2-adrenoceptor is a protein receptor that enables cells to respond to hormones. In breast cancer, this receptor causes more aggressive tumour cells to metastasise faster in response to stress. This proposal aims to understand why this response occurs in only very aggressive cells, and to identify how we can better target blocking drugs to this receptor. This could allow us to design better drugs with fewer side effects.
ASIC1a, A New Therapeutic Drug Target For Cardiac Ischemia
Funder
National Health and Medical Research Council
Funding Amount
$1,382,224.00
Summary
Cardiovascular disease is the biggest killer in the world, in large part due to the lack of drugs to protect the heart from the damage caused by injuries such as heart attack. Our team of world-leading scientists and clinicians has identified a novel therapeutic target (ASIC1a) against which drugs could be targeted to protect the heart against these injuries. The aim of this project is to develop novel cardioprotective drugs that target ASIC1a so we can test them in human clinical trials.
Understanding The Role Of Lipid In Membrane Permeabilization By The Bcl-2 Family Executioner Proteins
Funder
National Health and Medical Research Council
Funding Amount
$626,524.00
Summary
Apoptosis is a form of programmed cell death that protects our bodies from dangerous cells, e.g cells infected with viruses or that might become cancerous. A network of protein families control this process and this work will understand how certain members regulate a crucial step in this cell death pathway. Our studies will reveal key insights into apoptosis at the molecular level and inform the development of therapeutics for diseases characterised by dysregulated cell death such as cancer.
Sudden cardiac death (SCD) is a devastating consequence of a number of heart diseases. Underlying causes include inherited heart muscle problems (cardiomyopathies), with no cause found in 40%. Our study will investigate the role of 'concealed cardiomyopathy' cases, i.e. those with a SCD event with no evidence of heart disease, but carry errors in heart genes. Our findings will translate rapidly into more targeted clinical and genetic evaluation of families with the ultimate goal to prevent SCD.
Understanding The Molecular Mechanisms Of Cell Death In Radiotherapy
Funder
National Health and Medical Research Council
Funding Amount
$643,856.00
Summary
Radiotherapy (RT) is responsible for 40% of cancer cures. New technology enables RT delivery in fewer treatments using higher radiation dosages through a technique called 'ART'. While ART is effective in the clinic, the underlying mechanisms of cancer cell death are unclear. Here we show that ART induces two distinct waves of cancer cell death. We will characterize these waves of cell death and determine how to enhance tumour cell killing with pharmacological intervention.
Neuronal Regulation Of Systemic Mitochondrial Stress
Funder
National Health and Medical Research Council
Funding Amount
$865,605.00
Summary
Mitochondria are the powerhouses of cells. They generate energy from the food we eat and air we breathe. However, excess nutrients can cause mitochondrial stress and damage that lead to disease. The objective of this research is to understand how the brain regulates mitochondrial stress responses throughout the body. Therefore, this project will identify stress-response processes that are directly relevant to health and disease.
Investigating The Consequences Of Dysregulated Lipogenesis In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$600,647.00
Summary
Reprogramming of cellular metabolism is a hallmark of cancer. As such, there has been growing interest in developing strategies to exploit metabolism for therapeutic gain. Our ability to do this is dependent on a thorough understanding of the mechanisms by which dysregulation of cellular metabolism contributes to tumour progression. In this project, we seek to the investigate the fundamental mechanisms by which aberrant activation of lipid metabolism contributes to the tumourigenic process.
Betacellulin: Defining A Novel Sub-type In Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$907,515.00
Summary
Schizophrenia is a severe lifelong mental disorder affecting 0.7% of the world population with only partially effective symptomatic treatments. Its cause is unknown and thus cures cannot be developed currently. A promising candidate is betacellulin a growth factor which is very reduced in the brain and blood of people with schizophrenia. Little is known about its role in the brain and this project seeks to identify its relevance to schizophrenia as a step to develop new treatments.
Finely Tuned Glutamate Receptor Inhibitors As Novel Therapeutics For Neurodegenerative Disorders
Funder
National Health and Medical Research Council
Funding Amount
$1,168,829.00
Summary
Neurodegenerative disorders are among the leading causes of death and disease burden. New drugs are needed to treat both symptoms and disease progression. This project aims to understand the properties of different drug-like compounds to inhibit proteins on the surface of brain cells (glutamate receptors) to impact disease progression and symptoms in a preclinical disease models. The project will yield a better understanding of how best to target glutamate receptors for therapeutic effect.
A Novel, Actionable Pathway Promoting Metastasis Of Triple Negative Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$708,272.00
Summary
Triple negative breast cancer (TNBC) is particularly aggressive and lacks targeted therapies, limiting treatment to chemotherapy. A protein termed PEAK1 drives TNBC but has remained 'undruggable'. Recently, we identified an enzyme, termed CAMK2D, that acts downstream of PEAK1 and mediates its effects. In this grant we will characterize the mechanism of CAMK2D and determine the effect of a drug that blocks its action. This may lead to a new targeted and personalized treatment for TNBC.