Regulation Of Megakaryocyte And Platelet Survival In Malignancy
Funder
National Health and Medical Research Council
Funding Amount
$536,914.00
Summary
In this grant we will investigate how blood cells called platelets are produced in normal conditions and during disease. Platelets are blood cells that stop us from bleeding when we get a cut. When too many platelets accumulate, there is an increased risk of blood clots forming. This project grant will help us learn how platelet numbers swell in response to some blood and ovarian cancers, and the mechanisms that control cell death in platelets and the cells that produce them.
Bcl-2 Proteins And The Regulation Of The Megakaryocyte Lineage.
Funder
National Health and Medical Research Council
Funding Amount
$416,240.00
Summary
Platelets are tiny cells that circulate in the blood. They are essential for blood clotting. Too few platelets leads to uncontrolled bleeding. Platelets are produced in the bone marrow by cells called 'megakaryocytes'. Cancer chemotherapy often causes dangerous decreases in platelet count - this is thought to be because it kills megakaryocytes. We will pinpoint the molecules responsible for megakaryocyte life and death. This has the potential to make the side effects of chemotherapy less severe.
Tremor is the rhythmic shaking of a body part and is a common and disabling problem seen in diseases such as Parkinson’s disease and Essential Tremor. At present there is no single diagnostic test to determine the cause of a person’s tremor. This project aims to combine the use of sensors that measure tremor and muscle activity with clinical assessment to develop new tests for reliably diagnosing and monitoring tremor, a key step to treating patients correctly and conducting future drug trials.
The Regulation Of PI 3-kinase Second Messenger Molecules, PtdIns(3,4)P2 And PtdIns 3-P.
Funder
National Health and Medical Research Council
Funding Amount
$406,980.00
Summary
Cells respond to the external environment, hormones, and growth factors by generating messages inside the cell that send a signal to the nucleus that stimulates cell growth. One such signalling network is that produced by membrane lipids known as phosphoinositides. Enzymes that produce these signals are known as kinases. There has been considerable interest in the PI 3-kinase as the signals generated by this enzyme are increased in many human cancers. Inherited cancer syndromes have been describ ....Cells respond to the external environment, hormones, and growth factors by generating messages inside the cell that send a signal to the nucleus that stimulates cell growth. One such signalling network is that produced by membrane lipids known as phosphoinositides. Enzymes that produce these signals are known as kinases. There has been considerable interest in the PI 3-kinase as the signals generated by this enzyme are increased in many human cancers. Inherited cancer syndromes have been described that have lost the ability to switch off PI 3-kinase signals. The current project aims to investigate a recently identified enzyme called the 4-phosphatase that has the ability to terminate PI 3-kinase signals. Recent studies have shown this enzyme regulates cell growth. In addition key experiments have shown the enzyme is important as it may regulate certain strains of bacterial infection. This research proposal aims to investigate how the enzyme works to regulate these growth promoting signals. This may help us develop novel therapeutic strategies to control cell growth.Read moreRead less
A Bioinformatic Analysis And Structural Study On The Inositol Polyphosphate 5-phosphatases
Funder
National Health and Medical Research Council
Funding Amount
$421,320.00
Summary
Communication (or signaling) inside the cell enables the cell to respond to factors in its external environment, such as hormones or growth factors. The inositol phosphates and the phosphoinositides are signaling molecules that play an essential role in intracellular communication. The 5-phosphatases are able to modify these molecules and terminate, and in certain cases stimulate, signals. Failure to properly control intracellular signaling pathways may result in abnormal cell growth and cancer. ....Communication (or signaling) inside the cell enables the cell to respond to factors in its external environment, such as hormones or growth factors. The inositol phosphates and the phosphoinositides are signaling molecules that play an essential role in intracellular communication. The 5-phosphatases are able to modify these molecules and terminate, and in certain cases stimulate, signals. Failure to properly control intracellular signaling pathways may result in abnormal cell growth and cancer. Human 5-phosphatases are a complex family of enzymes: In addition to the region responsible for phosphatase activity (the catalytic domain) many members contain other protein modules . These associated domains may perform critical roles, such as regulating intracellular location and docking with other proteins. This project aims to perform a computational investigation of human 5-phosphatases and their associated domains. In particular we will search for novel phosphatases, investigate the evolutionary relationships between members of each domain family, and make testable predictions regarding the function of uncharacterized domains. This study will take advantage of data produced by the recently completed human genome project. The second aim of the project is to determine, using X-ray crystallography, the three-dimensional shape (or atomic structure) of a representative member of the 5-phosphatase family. Solving the structure of a 5-phosphatase at the atomic level is critical for understanding the nature of substrate specificity and for rational drug design.Read moreRead less
FUNCTIONAL IDENTIFICATION OF CORTICAL AND SUBCORTICAL SITES RESPONSIBLE FOR NEUROGENIC HYPERTENSION IN HUMANS
Funder
National Health and Medical Research Council
Funding Amount
$514,644.00
Summary
Blood pressure is normally maintained at a relatively constant level through reflexes involving the brainstem, but we have recently shown that higher areas of the brain are also involved in the regulation of blood pressure in humans. Here, we will use the novel methodologies we have developed to study functional and structural changes in the brain in patients with essential and renovascular hypertension.
RCT Of Omega-3 Fatty Acids As Treatment Of Subthreshold Symptoms In Young People At Ultra-high Risk For
Funder
National Health and Medical Research Council
Funding Amount
$280,102.00
Summary
Omega-3 fats are a type of polyunsaturated fat which has long been thought to be beneficial for health. The body cannot make its own omega-3 fats - they must be taken in through the diet, or in supplement form. Large population-based studies have suggested that a diet rich in omega-3 fats can reduce the risk of cardiovascular disease, lower blood pressure, cut the risk of cancers such as prostate and skin. The fats have also been touted as a treatment for arthritis, asthma, and inflamed bowels. ....Omega-3 fats are a type of polyunsaturated fat which has long been thought to be beneficial for health. The body cannot make its own omega-3 fats - they must be taken in through the diet, or in supplement form. Large population-based studies have suggested that a diet rich in omega-3 fats can reduce the risk of cardiovascular disease, lower blood pressure, cut the risk of cancers such as prostate and skin. The fats have also been touted as a treatment for arthritis, asthma, and inflamed bowels. A lack of omega-3s during foetal development can hinder brain and eye development. Other work has suggested that a diet rich in omega-3 may help improve mental health. Studies revealed beneficial effects in a broad range of mental health problems including violent and aggressive behaviour in teenagers, major depression, bipolar affective disorder, borderline personality disorder, and schizophrenia. Evidence that omega-3 fatty acids may reduce symptoms in schizophrenia and other major psychiatric disorders make omega-3 fatty acids an optimal candidate for further evaluation of its therapeutic efficacy, in particular in young people in early illness stages of psychosis where specific intervention is controversial due to potential risks and medication side-effects. The proposed 12-week intervention study aims to establish a new treatment strategy alternative to antipsychotic medication in the young people with subthreshold symptoms at high risk for psychosis. Omega-3 fatty acids have no clinically relevant side effects which often accompany therapy with antipsychotics (such as diabetes and weight gain). A widely available, easy applicable, biological treatment without clinically relevant side effects could help to improve compliance and outcome in psychosis. Schizophrenia is often prolonged and results in a considerable economic burden. Early treatment has the potential to offset future costs to both mental health providers and the recipients of these services.Read moreRead less