Characterisation Of The Growth Receptor Bound 7 (Grb7) Protein And Protein And RNA Partners Involved In The Regulation Of Stress Granule Formation And Cell Migration.
Funder
National Health and Medical Research Council
Funding Amount
$643,958.00
Summary
This proposal is to investigate the Grb7 protein that occurs at very high levels in some types of cancer cells, including breast cancer cells. It is thought that Grb7 contributes to the progression of cancer by directly affecting the regulation of other genes. We will investigate the way in which this protein interacts with other proteins and RNA that could underlie the cancer growth and spread. A better understanding of the Grb7 protein will help to establish its potential as a novel drug targe ....This proposal is to investigate the Grb7 protein that occurs at very high levels in some types of cancer cells, including breast cancer cells. It is thought that Grb7 contributes to the progression of cancer by directly affecting the regulation of other genes. We will investigate the way in which this protein interacts with other proteins and RNA that could underlie the cancer growth and spread. A better understanding of the Grb7 protein will help to establish its potential as a novel drug target.Read moreRead less
C-Jun N-terminal Kinase Actions In The Response To Stress
Funder
National Health and Medical Research Council
Funding Amount
$480,127.00
Summary
All cells in our body sense and respond to stressful changes in our environment. We are focused on enzymes called JNKs that relay this information, and so form part of the key response pathways. JNKs are now being evaluated as new drug targets for the treatment of diseases including diabetes and stroke, but we know very little about how JNKs work in stressed cells. We will define new partners for the JNKs and in so doing reveal new information on the stress-activated events they regulate.
Interactions Between Advanced Glycation And Oxidative Stress In Diabetic Renal And Cardiac Complications
Funder
National Health and Medical Research Council
Funding Amount
$431,700.00
Summary
Kidney and heart disease are serious complications of diabetes. These complications are the major cause of disability and premature death in the western world. Studies from our group and others have shown that diabetic complications appear to be a consequence of a number of different processes. These pathways include a sugar dependent pathway of irreversible interactions between proteins such as collagen and sugar known as advanced glycation. The process of advanced glycation alters the body's a ....Kidney and heart disease are serious complications of diabetes. These complications are the major cause of disability and premature death in the western world. Studies from our group and others have shown that diabetic complications appear to be a consequence of a number of different processes. These pathways include a sugar dependent pathway of irreversible interactions between proteins such as collagen and sugar known as advanced glycation. The process of advanced glycation alters the body's ability to renew these protein, hence causing accelration of the ageing process. In fact, it is estimated that this process occurs almost fifty times faster in diabetes. These sticky complexes accumulate in tissues causing disruption ot the normal tissue structure. Our group has a drug which can act as scissors and cut the sticky sugar off the proteins allowing it to be turned over. Unfortunately this does not fix all of the damage. These AGE molecules are involved in a number of other harmful processes including the production of toxic oxygen derived molecules which are harmful byproducts of diabetes. While these oxygen 'radicals' have been implicated in heart attack and stroke their source has remained a mystery in diabetes. Previously, the only way to remove these molecules was to mop them up with antioxidants such as Vitamin E. Antioxidants work slowly and so some damage is already done before they 'detoxify' these oxygen radicals. We propose to use combinations of medicines to see if we can achieve more effective protection against these processes in experimental diabetes. This may provide new therapies for threatment of kidney and heart disease in diabetes.Read moreRead less
Structure-function Inter-relationships Of Small Heat-shock Chaperone Proteins
Funder
National Health and Medical Research Council
Funding Amount
$240,990.00
Summary
In vivo, most proteins only function over a narrow temperature or pH range. For example, if the solution containing a particular protein is heated (stressed), the protein will unfold, aggregate and potentially precipitate. The act of protein precipitation is an irreversible process that, in many cases, has deleterious consequences for cell viability. Protein precipitation is associated with a diversity of diseases, e.g. cataract and neurodegenerative diseases such as Alzheimer's, Creutzfeldt-Jak ....In vivo, most proteins only function over a narrow temperature or pH range. For example, if the solution containing a particular protein is heated (stressed), the protein will unfold, aggregate and potentially precipitate. The act of protein precipitation is an irreversible process that, in many cases, has deleterious consequences for cell viability. Protein precipitation is associated with a diversity of diseases, e.g. cataract and neurodegenerative diseases such as Alzheimer's, Creutzfeldt-Jakob and Parkinson's diseases. Nature has evolved cellular mechanisms to minimise protein misfolding, aggregation and precipitation which principally utilise a diverse group of controlling or regulatory proteins called molecular chaperones. Amongst the most important of these are the small heat-shock proteins (sHsps) which are found in all organisms. sHsps function by interacting in a very efficient manner with destabilised proteins to prevent their precipitation. Little is known, however, about the structure of sHsps nor the mechanism by which they perform their chaperone action. This proposal will address these fundamental aspects via the use of a variety of spectroscopic techniques, principally nuclear magnetic resonance (NMR) spectroscopy.Read moreRead less
How well people perform in everyday situations is often determined by memory function. When required to perform under stress memory performance is often affected. The effect of a psychological stress test on memory function in healthy volunteers and the ability of a dietary supplement, tyrosine, to prevent the effects will be studied. The data may suggest that depletion amino acids is responsible for the decrements in performance that are evident after an acute stressor.
Central Control Of Stress-induced Changes In Immune Function.
Funder
National Health and Medical Research Council
Funding Amount
$411,724.00
Summary
LONG-TERM STRESS CAN ALTER OUR BRAIN'S ATTEMPTS TO FIGHT INFECTION Long-term stress is often blamed for causing illness but precisely how this occurs is now only beginning to be realised. It is especially disturbing that long-term stress can increase one's susceptibility to infections. Stress can alter the way our brain can help deal with assaults by bacteria and viruses. Normally, at the start of an infection, we release a hormone called cortisol from our adrenal glands. A low level of cortisol ....LONG-TERM STRESS CAN ALTER OUR BRAIN'S ATTEMPTS TO FIGHT INFECTION Long-term stress is often blamed for causing illness but precisely how this occurs is now only beginning to be realised. It is especially disturbing that long-term stress can increase one's susceptibility to infections. Stress can alter the way our brain can help deal with assaults by bacteria and viruses. Normally, at the start of an infection, we release a hormone called cortisol from our adrenal glands. A low level of cortisol in our body is beneficial because it can prevent the infection from taking hold in our body and spreading. However if we are chronically stressed our brains tell the adrenal glands to secrete excessive amounts of cortisol over long periods of time and this imbalance can actually hinder the ability of one's immune system to fight an infection. The unfortunate consequence is that the infection is more likely to win the battle and spread to cause further havoc. The present study will identify which areas of the brain are important in driving the secretion of cortisol during infection and how long-term stress can influence those areas. Because we might be exposed to long-term psychological stress that is repeated regularly or irregularly we will determine which pattern of stress has the greatest effect. An investigation into how the brain operates during long-term stress and infection will help us develop ways to prevent stress from disrupting our immune systems.Read moreRead less
Chronic or extreme reactions to stress can lead to pathological conditions such as long term anxiety states, depression and panic disorders. Stress related disease also contributes to other major health problems such as heart disease and disorders of the immune system. These disease states include some of the major medical problems of our times. This proposal is to define genes which may be involved in stress responsiveness, to further understand and treat stress related disease.
Cardiovascular Responses To Stress And Arousal: Hypothalamic And Brainstem Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$566,468.00
Summary
Stressful episodes in everyday life cause increases in blood pressure, mainly via activation of nerves that constrict blood vessels and increase heart rate. This in turn increases the risk of heart attacks, strokes, or other cardiovascular diseases. This project aims to identify the brain mechanisms that cause these stress-evoked effects. This knowledge may lead to much more effective ways of minimising stress-evoked responses, and thus reduce the risk of cardiovascular disorders.