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.
KLFs are master control genes that regulate the expression of many target genes to determine cell fate and to convert one cell fate to another. Mutations in KLFs cause human diseases. This grant will focus on the founding member of the KLF family, KLF1. We will use genomics techniques and animal models to determine how KLF1 works in normal blood cell production and in disease
Regulation Of The Haemostatic Activity Of Plasma Von Willebrand Factor
Funder
National Health and Medical Research Council
Funding Amount
$851,980.00
Summary
Our genes encode proteins that perform the tasks of life. Most proteins are chemically modified after they are made to control how, when, and where they function. Prof Hogg discovered a new chemical modification of proteins that is important in health and disease. He will apply this discovery to develop new diagnostics and therapies for heart attacks and stroke. Prof Hogg is one of the few Australians to take new diagnostics and therapies developed in the lab to evaluation in patients.
Estimation Of Transient Increases In Bleeding Risk Associated With Physical Activity In Children With Haemophilia
Funder
National Health and Medical Research Council
Funding Amount
$102,143.00
Summary
Haemophilia A and B are genetic conditions which affect 1 in 7,000 males in Australia. These disorders cause frequent bleeding due to problems with the clotting factor in blood. Over the past decade there has been a move to administer clotting factor to children with haemophilia in order to prevent bleeds and the consequent damage to joints that occurs when bleeds occur in a joint. Participation in vigorous physical activity and sport is thought to increase the risk of bleeding. Because of this, ....Haemophilia A and B are genetic conditions which affect 1 in 7,000 males in Australia. These disorders cause frequent bleeding due to problems with the clotting factor in blood. Over the past decade there has been a move to administer clotting factor to children with haemophilia in order to prevent bleeds and the consequent damage to joints that occurs when bleeds occur in a joint. Participation in vigorous physical activity and sport is thought to increase the risk of bleeding. Because of this, children are often given clotting factor prior to playing sport. However clotting factor is extremely expensive. For example, a boy wanting to play tennis three times a week would require three injections of cIotting factor per week at a cost of approximately $250,000 a year. To date there is no good evidence about which physical activities are likely to increase the risk of bleeding. If this information was available clinicians would be able to optimise timing of administration of clotting factor so that it is administered prior to activities associated with high risk of bleeds. Another reason to quantify risk of bleeds associated with activity is to inform decisions about participation in physical activity. Every boy with haemophilia wants to know if he can play sport or ride a skateboard or jump on a trampoline. Informed decisions about participation require accurate estimates of risk. This study will use an innovative design to provide, for the first time, accurate estimates of the risk of bleeding associated with physical activity. This information will form the basis for clinical practice guidelines regarding participation in physical activity.Read moreRead less
The BHLH Transcription Factor LYL1 In Normal And Leukemic Hematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$520,945.00
Summary
This project aims to understand how two closely related genes, called SCL and LYL1, work together to control the production of normal red blood cells and when abnormally expressed, cause cancer of the white blood cells. We will specifcially examine how LYL1 causes a specific type of leukemia in children and determine blocking the function of LYL1 will be a useful way to kill leukemia cells.