The Role Of Tissue Factor In The Regulation Of Extracellular Matrix Remodelling And Angiogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$241,980.00
Summary
The aim of the project is to understand how some blood clotting factors may be involved with the regulation of the extracellullar matrix (the material that exists between cells) and angiogenesis (new blood vessel formation). New blood vessel growth occurs in a wide variety of situations including: healing of a flesh wound, the healing phase following a heart attack, development of the eye disease associated with sugar diabetes, in and around a cancerous growth, in the uterus during the normal me ....The aim of the project is to understand how some blood clotting factors may be involved with the regulation of the extracellullar matrix (the material that exists between cells) and angiogenesis (new blood vessel formation). New blood vessel growth occurs in a wide variety of situations including: healing of a flesh wound, the healing phase following a heart attack, development of the eye disease associated with sugar diabetes, in and around a cancerous growth, in the uterus during the normal menstrual cycle, and for the normal growth and development of the placenta and a new baby. The processes by which these new blood vessels form and the factors contributing to the maintenance of their structure are incompletely understood. However, it is known that the interaction of cells and the surrounding extracellular matrix is critical for normal cell function and in particular for new blood vessel formation. Studies in this project will seek to define a relationship between some of the factors which regulate blood clotting, and those that regulate turnover of the extracellular matrix and new blood vessel formation. In particular, how blood clotting factors may be invovled in the regulation of the extracellular matrix will be studied in a rapidly developing tissue, the mouse placenta. The role of blood clotting factors in regulation of new blood vessel formation into an artificial avascular tissue will also be examined. These studies will employ some of the new genetic techniques to understand new roles for proteins which have been traditionally thought to act in only one way. This research has the potential to provide new insights into how blood vessels are formed and are subsequently maintained. This increased understanding will provide the knowledge required for the development of new therapeutic strategies to correct the process when it goes wrong, is unwanted or underdeveloped in human disease.Read moreRead less
Identifying The Pathological Mechanism Of Polyalanine Expansion Mutations In The X-linked Hypopituitarism Gene SOX3
Funder
National Health and Medical Research Council
Funding Amount
$402,846.00
Summary
Mental retardation (MR) is a debilitating disorder which affects 1-3% of the population. In many cases, MR results from changes (mutations) in genes which regulate the development of the brain before birth. We are studying families with an inherited form of MR termed X-linked Hypopituitarism (XH) in which only boys are affected. In addition to intellectual disability, boys with XH also have poor pituitary function resulting in short stature and slow metabolism. In severe cases, where the pituita ....Mental retardation (MR) is a debilitating disorder which affects 1-3% of the population. In many cases, MR results from changes (mutations) in genes which regulate the development of the brain before birth. We are studying families with an inherited form of MR termed X-linked Hypopituitarism (XH) in which only boys are affected. In addition to intellectual disability, boys with XH also have poor pituitary function resulting in short stature and slow metabolism. In severe cases, where the pituitary has failed to form completely, these babies are extremely ill and in some instances do not survive. We have previously shown that XH is due to an unusual change in the SOX3 gene in which the number of consecutive alanine residues is increased above a critical threshold (polyalanine expansion mutations). Similar mutations have recently been identified in several other genes that also cause severe birth defects. However, little is currently known about how polyalanine expansion mutations cause these disorders. The overall aim of this proposal is generate a mouse model for this disorder. Analysis of these mice will help us to answer many unresolved questions about this disorder including: How does the mutant protein cause this disorder? Which parts of the brain and pituitary are affected and how is their function altered? How does the mutant protein affect other genes and proteins in the cell? Ultimately, we hope that this mouse model will help us to develop new and improved therapies for XH and other disorders that are caused by alanine expansion mutations.Read moreRead less
Genotypes And Phenotypes Of Human Primary Non-congenital Antibody Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$544,692.00
Summary
Antibodies represent a key component of the immune system, and a particularly important in defence against bacterial and viral infections. In some individuals, antibody production fails, rendering them more susceptible to infection. In most cases, the mechanism of antibody failure is unknown. This project seeks to determine the genetic and cellular mechanisms of antibody failure. This could improve diagnosis for immune deficiency, and improve our overall understanding of the immune system.
Factor XII-dependent Thrombosis And Platelet Glycoprotein Ib
Funder
National Health and Medical Research Council
Funding Amount
$336,767.00
Summary
We will determine the value of targeting the interaction between a receptor unique to platelets, glycoprotein Ib, and two factors (XI and XII) in plasma involved in blood clotting, as a novel strategy to prevent clots that lead to heart attack-stroke. Our study is at the basic research-clinical interface and has the potential to improve our understanding of both bleeding in patients with Factor XI-XII defects and prevention of dangerous levels of clotting without affecting normal vessel repair.