Determining recurrence risk in breast cancer is crucial, as more than half of all recurrences occur after 5 years. However, optimal management of breast cancer is hampered by the challenges in finding rational preventative and predictive targets. Our vision is to find targets responsible for progenitor cell expansion, as candidates for prevention, and to find markers of relapse, to predict early versus late responders to therapy.
A common characteristic of cancer is the failure of cells to die when they normally would. One of the problems with many cancer therapies is that they rely on the integrity of signalling pathways to the normal ‘death machinery’ of the cell to do their job. By understanding how the molecular death machine operates we are fashioning new drugs that can target it directly, thus bypassing the very pathways that are so frequently disrupted in tumour cells.
Peptides (mini proteins) have outstanding potential as new drugs for cancer, pain and many other diseases, but their potential has not been realised so far because peptides tend to be unstable in the body. I have discovered a new class of peptides that are ultra-stable and have very favourable pharmaceutical properties. I will use these peptides to develop a new generation of drugs that are more potent and with fewer side effects than traditional drugs.
Hepatitis C virus (HCV) and Human immunodeficiency virus (HIV) infect 200 million and 50 million people world-wide, respectively, and there are no preventative vaccines. The work outlined in this fellowship seeks to understand the structure and function of the major surface proteins of these viruses, their ability to be recognised by the immune system and to develop a novel vaccine for the prevention of HCV.
Despite dramatic improvements in diagnosis, prevention and treatment of heart disease, cardiovascular disease remains the commonest cause of death in Australia. The continuing decline in mortality from ischaemic heart disease has been offset by an increase in the incidence of sudden cardiac death due to abnormal heart rhythms. By understanding the basic mechanisms underlying cardiac arrhythmias we are seeking to develop more effective therapies to treat and/or prevent sudden cardiac death.
Venoms To Drugs: Translating Venom Peptides Into Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$751,854.00
Summary
Chronic pain is a major global health problem that currently affects over three million Australians. There are few drugs available for treating chronic pain and many have significant side-effects. Several ion channels are critical for conducting pain signals to the brain. Blocking these channels can provide pain relief and, in some cases, protection from brain injury following stroke. We are producing potent and selective blockers of these ion channels for the treatment of chronic pain and strok ....Chronic pain is a major global health problem that currently affects over three million Australians. There are few drugs available for treating chronic pain and many have significant side-effects. Several ion channels are critical for conducting pain signals to the brain. Blocking these channels can provide pain relief and, in some cases, protection from brain injury following stroke. We are producing potent and selective blockers of these ion channels for the treatment of chronic pain and stroke.Read moreRead less
Biomarkers For The Diagnosis And Prognostic Analysis Of Male Infertility
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
Male infertility is a common condition, affecting 1 in 15 men. Although a standard semen analysis is often performed to test whether a man is infertile, it is far from definitive. We have developed a new approach, by looking at proteins that are commonly missing from infertile sperm cells. From this analysis, we can definitively diagnose male infertility and are beginning to understand why men are becoming infertile.
Detailed images of protein molecules underpin our understanding of biological function and our attempts to find new medicines to counter biological malfunction. Proteins belonging to the so-called Bcl-2 family determine whether a cell lives or dies and, because failure to die on cue is a hallmark of many cancers, high resolution images of these molecules will reveal new targets for cancer therapies.
The nuclear hormone receptors (NRs) translate hormonal, metabolic & pathophysiological signals into gene regulation, and several NRs are very important in human health. NRs are important therapeutics targets in the treatment of dyslipidemia, insulin insensitivity and breast cancer. Our data identifies new and novel NR targets that can be therapeutically/pharmacologically exploited in the context of exercise capacity, metabolic disease and breast cancer.
My research is aimed at understanding how the structure and dynamics of proteins dictates their function. I use X-ray crystallography to determine the shapes of proteins. Proteins are not static, however - they move in complicated ways, and often their motion is critical to their function (molecular motors, for example). It is very difficult to 'watch' this movement in the lab, so I use computer simulation to try to understand how proteins move.