The Role Of ERK MAPKs In Compensated Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$241,650.00
Summary
According to recent statistics, heart failure accounts for almost 300 deaths each year in Australia. In fact, heart failure is now a major health problem that is on the rise, despite the reduced incidence of other forms of heart and blood vessel disease. We are now in the situation where the cost of treatment of heart failure exceeds that of treating all cancer patients, and there are more patient days in hospital with heart failure than with any other heart or blood vessel disease. Most often, ....According to recent statistics, heart failure accounts for almost 300 deaths each year in Australia. In fact, heart failure is now a major health problem that is on the rise, despite the reduced incidence of other forms of heart and blood vessel disease. We are now in the situation where the cost of treatment of heart failure exceeds that of treating all cancer patients, and there are more patient days in hospital with heart failure than with any other heart or blood vessel disease. Most often, the heart fails to act as an effective pump following long-term exposure to high blood pressure. The increased work load placed on the heart effectively forces it to increase in size in a process called cardiac hypertrophy. But this initial compensation which is of benefit to the patient commonly deteriorates and many of the heart cells die. The resulting death of heart cells is the failure of the heart, and death of the patient is inevitable. The fundamental changes in the functional protein molecules of the heart cells that accompany hypertrophy and heart failure are likely to be extremely complex. As yet, no research has taken a global and unbiased look into this complexity. However, there are new technologies that allow us to take such a look. We have established a collaborative research team to investigate the fundamental mechanisms underlying cardiac hypertrophy. We are exploiting a novel model in which hypertrophy does not progress to failure. Our combined expertise allows us to use recently developed scientific methodologies to evaluate the biochemical basis for these events in the heart. We have chosen to focus on documenting the changes in proteins that accompany cardiac hypertrophy with the aim to establish important targets for interventions to permit cardiac cells to survive despite hypertrophy. This will have important implications for preventing cardiac failure.Read moreRead less
Making Signalling Through The Tumour Necrosis Factor Receptors Selective For Promoting Neutrophil Antimicrobial Activity
Funder
National Health and Medical Research Council
Funding Amount
$196,312.00
Summary
It is evident to the professional and general community that antibiotic and drug resistance displayed by bacteria is a continuing and growing problem in the treatment of infection with potentially casastrophic effect on the health of our community. This concern is only partly reduced by our potential to develop new antimicrobial agents and vaccines. If we were able to use immunomodulators in a relatively safe and appropriate manner to target and enhance the antimicrobial power of specific compon ....It is evident to the professional and general community that antibiotic and drug resistance displayed by bacteria is a continuing and growing problem in the treatment of infection with potentially casastrophic effect on the health of our community. This concern is only partly reduced by our potential to develop new antimicrobial agents and vaccines. If we were able to use immunomodulators in a relatively safe and appropriate manner to target and enhance the antimicrobial power of specific components of the immune system then this could be exploited in the treatment of infection. While body proteins formed (cytokines) which modify the behaviour of the immune system are being used as pharmaceuticals, their toxic side effects are problematic to the patient. Our project focusses on one of the cytokines, tumor necrosis factor (TNF), which increases the antimicrobial activity of phagocytic cells but in addition can have quite devastating effects on other tissues in the body. This is because when TNF binds to its receptor on cells and tissues it elicits a multitude of signals inside the cell which can also precipitate illness. The purpose of our investigations is to identify which signals are responsible for increasing resistance against infection and which are not. With this information we will then see if it is feasible to selectively stimulate this signal from outside the cell since this has a better chance of succeeding as a pharmaceutical. This task is likely to be achievable since our research team has made some unique observations about TNF signalling characteristics and we have developed a peptide TNF mimetic which shows only the characteristics of increasing antimicrobial activity.Read moreRead less
MKP-1 As A Novel Anti-inflammatory Strategy In Asthma And Airway Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$461,528.00
Summary
Asthma is a chronic disorder where airways are remodelled, or thickened, resulting in poor lung function. Airway remodelling is a consequence of long-term inflammation after multiple episodes of asthma. As the current drugs to treat remodelling have side effects, the aim of this grant is to investigate a novel anti-inflammatory strategy to reverse the development of airway remodelling by increasing the anti-inflammatory protein - MKP-1.