Is The Tumour Suppressor Activity Of P53 Independent Of Its Transcriptional Role?
Funder
National Health and Medical Research Council
Funding Amount
$162,920.00
Summary
To become cancerous, a cell must avoid death. As such, cancer cells often contain defects in cell death pathways which render them resistant to pro-death stimuli, including many chemotherapeutic drugs. To design new and better cancer therapies, it is essential that we understand the critical molecular processes that control cell death. This will allow the development of more effective ways to either reset, or bypass, defects in cell death pathways which have contributed to cancer formation.
Investigating Mitochondrial Outer Membrane Permeabilization During Programmed Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$88,065.00
Summary
Cancer cells often contain defects which prevent their death. To kill cancer cells we must either reset or bypass these defects. Release of cytochrome c from mitochondria is a critical event in cell death and proteins that block this event render cells resistant to many cancer therapies. My research will determine how cytochrome c release occurs, how this event is regulated and how to kill cancer cells in which cytochrome c release is blocked.
Conditional Gene Targeting Of An X-linked Activator Of Cytochrome C: Modelling Of An Infantile Cardiomyopathy.
Funder
National Health and Medical Research Council
Funding Amount
$183,266.00
Summary
Irregularities in heart rhythms are a significant cause of sudden and unexpected death in infants. The past few years has seen a dramatic increase in the identification of genetic abnormalities underlying such irregularities. In particular, a significant proportion of these abnormalities (known as mitochondriopathies) have been shown to be due to deficiencies or defects in the mitochondrial DNA, which encodes some of the components necessary for the generation of cellular energy stores. In contr ....Irregularities in heart rhythms are a significant cause of sudden and unexpected death in infants. The past few years has seen a dramatic increase in the identification of genetic abnormalities underlying such irregularities. In particular, a significant proportion of these abnormalities (known as mitochondriopathies) have been shown to be due to deficiencies or defects in the mitochondrial DNA, which encodes some of the components necessary for the generation of cellular energy stores. In contrast, surprisingly few examples exist where this type of disorder has been shown to be due to a defect in the DNA from the nucleus, despite the numerous components it encodes. We have strong genetic and biochemical evidence to suggest that a new gene (encoded by the nuclear DNA) underlies the sex-linked disorder, oncocytic cardiomyopathy, the major clinical features of which are sudden and irregular heart rhythms usually causing death in female infants before the age of two years. We will utilise a new and powerful genetic technique to reproduce the disorder in laboratory mice to enable a thorough investigation into how the disease manifests itself. It is hoped that this disease model will provide valuable clues towards our understanding of other disorders with sudden heart rhythm abnormalities. It may also give additional support to the likelihood that similar nuclear-encoded defects contribute to the prevalence of, and-or susceptibility to, sudden infant mortality. The novel approach taken will also, for the first time, directly investigate the mechanisms that govern the severity of presentation of the disease in females. These studies will also complement other biochemical studies that are ongoing in our laboratory and will likely have implications for the clinical presentation of numerous other X-linked genetic disorders.Read moreRead less
Engineering CYP17A1 Inhibitors For Castrate-resistant Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$519,428.00
Summary
As prostate cancer progresses it becomes resistant to first line treatments and the current second line treatments have untoward side effects. This proposal will provide proof of principal for new selective drugs to be developed. We propose an innovative strategy to develop new selective drugs for the treatment of prostate cancer. This new therapeutic approach will identify new compounds for patients specifically with castrate sensitive and resistant prostate cancer.