Improving Patient Outcomes Through Better Use Of Blood Products
Funder
National Health and Medical Research Council
Funding Amount
$1,412,250.00
Summary
Blood transfusions, used wisely, save lives. Blood must be used judiciously: it is donated by volunteers, and carries risks and great cost to the community. Although a common intervention, evidence in many areas is inadequate to formulate recommendations on how blood should be used. This research program will address national priorities where evidence is weak by undertaking clinical trials to compare transfusion strategies, evaluate alternatives to transfusion and test novel blood components.
We want to understand more about the control of blood cell formation and the development of leukemia. We have discovered one gene that is very important in both these processes. It is the most common genetic abnormality involved in causing human T-cell leukemia, and we have recently shown that it is absolutely required for the development of all blood cells within an animal. We wish to take these observations further so that we can ultimately understand how a gene important in blood cell formati ....We want to understand more about the control of blood cell formation and the development of leukemia. We have discovered one gene that is very important in both these processes. It is the most common genetic abnormality involved in causing human T-cell leukemia, and we have recently shown that it is absolutely required for the development of all blood cells within an animal. We wish to take these observations further so that we can ultimately understand how a gene important in blood cell formation can also be important in causing leukemia. Here we propose to use genetic engineering approaches to generate mice in which the function of this gene is ablated or removed in a controlled and regulated fashion.Read moreRead less
Analysis Of The Hematopoietic Function Of Endophilin And MASH Proteins
Funder
National Health and Medical Research Council
Funding Amount
$408,055.00
Summary
We want to understand more about the control of blood cell formation and the development of leukaemia. We have discovered one gene that is very important in both these processes. It is the most common genetic abnormality involved in causing human T-cell leukaemia and we have recently shown that it is absolutely required for the development of all blood cells within an animal. We wish to understand how a gene important in blood cell formation can also be important in causing leukaemia. To address ....We want to understand more about the control of blood cell formation and the development of leukaemia. We have discovered one gene that is very important in both these processes. It is the most common genetic abnormality involved in causing human T-cell leukaemia and we have recently shown that it is absolutely required for the development of all blood cells within an animal. We wish to understand how a gene important in blood cell formation can also be important in causing leukaemia. To address this we will study a new molecule with which it partners, and two molecules via which it exerts its actions.Read moreRead less
We want to understand more about the control of blood cell formation and the development of leukaemia. We have discovered one gene that is very important in both these processes. It is the most common genetic abnormality involved in causing human T-cell leukaemia and we have recently shown that it is absolutely required for the development of all blood cells within an animal. We wish to take these observations further so that we can ultimately understand how a gene important in blood cell format ....We want to understand more about the control of blood cell formation and the development of leukaemia. We have discovered one gene that is very important in both these processes. It is the most common genetic abnormality involved in causing human T-cell leukaemia and we have recently shown that it is absolutely required for the development of all blood cells within an animal. We wish to take these observations further so that we can ultimately understand how a gene important in blood cell formation can also be important in causing leukaemia. To address this we will generate new models of blood cell development.Read moreRead less
Identification And Characterisation Of Human Telomerase Holoenzyme Components
Funder
National Health and Medical Research Council
Funding Amount
$325,091.00
Summary
DNA is packaged into linear structures - chromosomes - that have two ends, called telomeres. When cells proliferate, their telomeres normally shorten slightly, and this ultimately limits the number of times cells can proliferate. This limitation is thought to contribute to ageing. Some tissues normally have a high rate of cell turnover (for example in the bone marrow which is constantly producing large numbers of new blood cells), and therefore a need for very extensive cellular proliferation. I ....DNA is packaged into linear structures - chromosomes - that have two ends, called telomeres. When cells proliferate, their telomeres normally shorten slightly, and this ultimately limits the number of times cells can proliferate. This limitation is thought to contribute to ageing. Some tissues normally have a high rate of cell turnover (for example in the bone marrow which is constantly producing large numbers of new blood cells), and therefore a need for very extensive cellular proliferation. In these tissues, an enzyme called telomerase slows down (but does not completely prevent) the rate of telomere shortening by replacing some of the DNA that is lost as a result of proliferation. Telomerase is a complex enzyme with a number of subunits. In the past few years, it has started to become clear that inherited deficiencies of some of these subunits cause diseases in which cellular proliferation starts to fail at a young age. These patients typically die of bone marrow failure. In contrast to conditions where there is telomerase deficiency, the great majority of cancers have inappropriately high levels of telomerase activity which allow cancer cells to continue dividing without limit. Telomerase is therefore regarded as a very promising target for new cancer treatments. In view of the importance of telomerase to human health, it may seem very surprising that we do not yet know all of its subunits. The reason for this is that, even in telomerase-positive cancer cells, the amount of telomerase present is vanishingly small which has made it impossible so far to obtain sufficient quantities for even the most sensitive analytical techniques. We are using very large numbers of human cells grown in a bioreactor, and have devised a highly efficient method for purifying telomerase from them. We will analyse the purified telomerase by contemporary mass spectroscopy techniques, identify all of the subunits, and characterise their contribution to telomerase function.Read moreRead less
Structure, Assembly, And Inhibition Of The Human Telomerase Enzyme Complex
Funder
National Health and Medical Research Council
Funding Amount
$645,359.00
Summary
In contrast to the limited growth of normal human cells, cancer cells proliferate out of control and without limit. At least 85% of all human cancers rely on the enzyme TELOMERASE to sustain their unlimited proliferation. Telomerase is absent in most normal tissues and therefore represents a potentially effective and specific target for future cancer therapy. We aim to determine the precise 3-dimensional shape of human telomerase to provide a template for rational anti-telomerase drug design.
Erythropoiesis Stimulating Agents are used to correct the anaemia associated with kidney disease, and cost Australia around $100m in 2004. The optimal target haemoglobin remains the subject of intense debate despite several large trials in the area. This project will use pooled data from these trials to provide a definitive analysis of the overall harms and benefits associated with different targets for the first time and will guide the use of these expensive drugs to maximise patient benefit.
So Like Your Mum! Is The Health Of Mothers In Far North Queensland Reflected In The Nutrition And Growth Of Their Children In Early Life?
Funder
National Health and Medical Research Council
Funding Amount
$96,631.00
Summary
The health, nutrition and growth of a baby reflect the health and nutrition status of its mother. We will link routine health service information for Indigenous mothers with information on the growth, haemoglobin and health of their young children to identify key factors in a mother’s pregnancy and before, influencing the future health and development of their babies. This study will shape interventions to improve the health of mothers, and thus improve the health of their children through life.
We will investigate how the master control gene, Kruppel-like factor 1, orchestrates production of red blood cells. We will use genetic and cell biology approaches to determine exactly how this factor interprets the genome blueprint in a cell specific manner. We will also determine how mutations in KLF1 cause human diseases such as congenital dyserythropoietic anemia and hereditary persistence of fetal haemoglobin. This has implications for reactivation of HbF in adults with sickle cell disease.
Myelodysplastic Syndrome And The Bone Marrow Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$562,654.00
Summary
We are interested in how myelodysplastic syndrome (MDS) affects the function of the bone marrow. We believe that changes associated with anaemia of MDS cause the bone marrow to be altered. This proposal addresses this question and explores new treatment approaches