Therapeutic Implications Of A Molecular Link Between Survivin And Telomerase Reverse Transcriptase
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
A unifying feature of all types of cancer cells is that they are immortal. Our investigations will build upon our recent results that showed the gene survivin is involved in cancer cell immortalisation. We will characterise a molecular link between survivin and the enzyme telomerase, which is central to cancer cell immortality. Furthermore, we will demonstrate the therapeutic potential of turning off both survivin and telomerase as a novel approach to halting the growth of cancer cells.
The Nutritional Geometry Of Ageing In A Rodent Model
Funder
National Health and Medical Research Council
Funding Amount
$979,269.00
Summary
A central belief in ageing research is that eating fewer calories prolongs life, and that the source of calories (carbohydrate, fat or protein) is irrelevant. However, a critical assessment indicates that this conclusion is premature. We will use recent techniques in nutrition to define for the first time in mammals the relationship between diet and ageing in a normal and a prematurely ageing strain of mice. The project will provide a novel nutritional approach for promoting healthy ageing.
Selective Estrogen Receptor Modulators (SERMs) - A Potential New Treatment For Women Of Child-bearing Age With Psychotic Symptoms Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$210,480.00
Summary
Schizophrenia is a devastating illness urgently requiring a new treatment approach. We have discovered that estrogen is an effective treatment for women with schizophrenia and are currently trialling a safer Selective Estrogen Receptor Modulator (SERM) known as brain estrogen� in postmenopausal women with schizophrenia. Regulatory permission is now available to trial the SERM in younger women, and we seek to extend our current SERM study into child bearing age women with schizophrenia.
Mechanisms Of Proteolysis Of Proteins Containing Oxidised Amino Acids
Funder
National Health and Medical Research Council
Funding Amount
$406,320.00
Summary
There is evidence that during ageing, and age-related diseases, proteins which have been chemically modified by oxidation accumulate in the body, and may have deleterious effects. Oxidation of proteins is a process akin to that by which fats go rancid. It has been demonstrated by the applicants to be an important process in formation of cataracts, and in development of the blood vessel disease, atherosclerosis, which is responsible for most heart attacks and stroke. Other important age-related d ....There is evidence that during ageing, and age-related diseases, proteins which have been chemically modified by oxidation accumulate in the body, and may have deleterious effects. Oxidation of proteins is a process akin to that by which fats go rancid. It has been demonstrated by the applicants to be an important process in formation of cataracts, and in development of the blood vessel disease, atherosclerosis, which is responsible for most heart attacks and stroke. Other important age-related diseases, such as Alzheimer s disease and other neurological disorders, are also claimed to be associated with deranged protein oxidation, and accumulation of oxidised products. There is clear evidence that certain defensive mechanisms, such as those acting to remove invading organisms and clear wounds, are also associated with an enhanced production of oxidised proteins. Perhaps the most important component of defense against oxidised proteins is their removal by complete breakdown to constituent components, and excretion. Normally, the machinery for breakdown of proteins is in vast excess over the required rate of degradation. However, clearly in these conditions of accumulation of oxidised proteins, this is no longer the case, or no longer suffices. Mechanisms by which oxidised proteins are degraded are poorly understood, and quite controversial. Therefore, the present studies bring to bear a new approach to studying this issue, which has been developed by the applicants. The aim is to reveal mechanisms involved in the breakdown of proteins containing oxidised amino acids, both in cellular systems, and in vivo. Such an understanding may allow us to envisage how to remove oxidised proteins by therapeutic means and therefore interfere with the development of age-related diseases such as Alzheimer s disease and cataract formation and the diseases of the blood vessels associated with attack and stroke.Read moreRead less
A Cognitive And Neuroimaging Study Of Exceptionally Old Individuals: Sydney Centenarian Study
Funder
National Health and Medical Research Council
Funding Amount
$857,197.00
Summary
Australia has an ageing society. Individuals over the age of 95 years are the fastest growing proportion of this population. Many of these individuals retain good cognitive function. The Sydney Centenarian Study will recruit all individuals 95 and over in 7 local government areas in Sydney to assess their brain function to determine which cognitive faculties are more or less affected, and how this relates to changes on brain scans. This will be related to neuropathology.
Osteoporosis is a major and increasing public health problem. Fracture, the ultimate consequence of osteoporosis is associated with significant morbidity, mortality and economic costs. The Dubbo Osteoporosis Epidemiology Study, starting in 1989, with over 2000 women and men, is one of the longest running epidemiological studies in osteoporosis worldwide. It has been at the forefront of epidemiological advances in osteoporosis. It has identified osteoporotic fracture risks including low bone dens ....Osteoporosis is a major and increasing public health problem. Fracture, the ultimate consequence of osteoporosis is associated with significant morbidity, mortality and economic costs. The Dubbo Osteoporosis Epidemiology Study, starting in 1989, with over 2000 women and men, is one of the longest running epidemiological studies in osteoporosis worldwide. It has been at the forefront of epidemiological advances in osteoporosis. It has identified osteoporotic fracture risks including low bone density and bone loss, muscle weakness and postural instability, as well as the extent of the problem in men, and the significant costs, ill-heath and mortality associated with fracture. Despite the clarification of risk factors over the past decade, there are significant gaps in knowledge about osteoporosis, particularly in the accurate prediction of fracture risk and in identification of factors related to fracture-associated mortality and survival post fracture. Although bone density is one of the best predictors of fracture risk, it incompletely discriminates between those who will fracture from those who will not. Although a number of clinical risk factors, and other measures of bone strength, such as quantitative ultrasound and geometry, have been shown to be independent predictors of fracture risk, it is not clear that these measures can be integrated with BMD to improve fracture prediction. The aim of the current study, is to develop and validate models using bone density, other measures of bone strength and clinical parameters that will more accurately predict fracture risk and mortality following fracture in older men and women. The more precise identification of those at high risk of fracture and at risk for poor outcomes following fracture will provide a rational basis for the development of more cost effective interventions for prevention of fracture and its associated morbidity and mortality.Read moreRead less
Inhibition Of Fear Memories By Extinction: Neural Substrates.
Funder
National Health and Medical Research Council
Funding Amount
$234,250.00
Summary
Anxiety disorders [e.g., Post Traumatic Stress Disorder (PTSD)] are the most prevalent type of psychopathology in the industrialised world. They are associated with characteristic behavioural (e.g., heightened startle) and autonomic (e.g., cardiovascular) reactions. These disorders are often characterised as an inability to regulate the emotion of fear. Significant progress has been made in understanding the neural and cellular processes involved in the establishment of fear memories, but relati ....Anxiety disorders [e.g., Post Traumatic Stress Disorder (PTSD)] are the most prevalent type of psychopathology in the industrialised world. They are associated with characteristic behavioural (e.g., heightened startle) and autonomic (e.g., cardiovascular) reactions. These disorders are often characterised as an inability to regulate the emotion of fear. Significant progress has been made in understanding the neural and cellular processes involved in the establishment of fear memories, but relatively little is known about the mechanisms by which fear memories can be inhibited or suppressed. Understanding this latter process is a key to the development of effective treatments for anxiety disorders such as PTSD where the patient suffers from persistent, intrusive, unwanted trauma memories. A common experimental procedure for reducing learned fear is to repeatedly expose the subject to a fear-eliciting stimulus but without any aversive outcome. This procedure leads to a progressive loss, or extinction, of the fear reactions elicited by the stimulus. Historically, the extinction of fear was thought to be due to an erasure of the fear memory. However, recent evidence shows that extinction inhibits, rather than erases, the fear memory. Because the fear memories remain intact, some structure(s) in the brain must inhibit activity in the fear pathway. This project uses extinction of conditioned fear reactions in rat subjects to determine the structure(s) in the brain that inhibit fear memories and their behavioural and cardiovascular expression. It brings together the expertise of four well-established researchers and uses a combination of behavioural, physiological, immunohistochemical, tract tracing, and lesion approaches to achieve this aim. The proposed experiments will reveal the structure(s) in the brain that control the inhibition of fear, as well as the site(s) of this inhibition in the fear pathwayRead moreRead less