Platelet Receptor Shedding In Stroke And Thrombosis
Funder
National Health and Medical Research Council
Funding Amount
$552,503.00
Summary
In response to tissue injury and bleeding, blood platelets use receptors to form a thrombus (blood clot) and block further loss of blood and aid tissue repair. In inflammation or disease, abberant platelet activation can form a thrombus within cerebral (stroke) or coronary vessels (heart attack). We examine how a thrombus-limiting step (platelet receptor shedding) is triggered in thrombus-forming platelets, and if shed receptor can be used as a blood marker of abberant platelet activation.
This project seeks to identify blood borne biomarkers that may be used, at the first antenatal visit, to identify women at risk of developing complications of pregnancy, If women at risk can be identified early opportunity is afforded to improve outcome for both mother and baby.
An Evaluation Of Inhibin And Activin As Early Markers Of Pre-eclampsia And Fetal Growth Restriction.
Funder
National Health and Medical Research Council
Funding Amount
$96,921.00
Summary
Pre-eclampsia and fetal growth problems are among the major causes of maternal and perinatal death in Australia. One of the most pressing difficulties in the management of these conditions is our present inability to accurately predict those women who are destined to have one or other of these serious complications. Unfortunately, this means that the conditions are often detected late with little or no time to offer effective treatments. This project builds on exciting preliminary evidence that ....Pre-eclampsia and fetal growth problems are among the major causes of maternal and perinatal death in Australia. One of the most pressing difficulties in the management of these conditions is our present inability to accurately predict those women who are destined to have one or other of these serious complications. Unfortunately, this means that the conditions are often detected late with little or no time to offer effective treatments. This project builds on exciting preliminary evidence that suggests that a simple blood test from the mother in early pregnancy may be able to identify the women who will subsequently develop high blood pressure in late pregnancy, or the babies that will suffer impaired growth before delivery. In the future, such knowledge might then allow these women to receive more effective care, thereby improving their chance of a successful pregnancy. The project will also define the best time in pregnancy to perform the blood test and, if successful, could alter the very way women are currently looked after during their pregnancy.Read moreRead less
Probing UDP-glucuronosyltransferase Protein-protein Interactions: The Power Of Two.
Funder
National Health and Medical Research Council
Funding Amount
$482,710.00
Summary
Drugs and other chemicals (eg. dietary constituents, environmental pollutants, and chemicals that occur naturally in the body - such as steroid hormones) are broken down by specialised proteins called enzymes. This process is referred to as biotransformation, or 'metabolism'. Drug and chemical metabolism serves as a detoxification mechanism (since the products of metabolism generally lack biological activity) and as a means of eliminating these substances from the body. UDP-Glucuronosyltransfera ....Drugs and other chemicals (eg. dietary constituents, environmental pollutants, and chemicals that occur naturally in the body - such as steroid hormones) are broken down by specialised proteins called enzymes. This process is referred to as biotransformation, or 'metabolism'. Drug and chemical metabolism serves as a detoxification mechanism (since the products of metabolism generally lack biological activity) and as a means of eliminating these substances from the body. UDP-Glucuronosyltransferase (UGT) is one of the most important enzymes involved in drug and chemical metabolism. Consistent with its ability to metabolise such a large number of compounds, UGT is known to exist as a 'superfamily' of structurally related proteins. Despite the importance of UGT, little is known about the structural characteristics of these enzymes that are responsible for recognising and binding different classes of chemicals. Accumulating evidence from this and other laboratories indicates that the individual UGT proteins may combine with themselves (to form a homodimer) and with other UGT proteins (to form heterodimers). This project largely seeks to define the scope of UGT homo- and hetero- dimerisation, identify the structural elements of the proteins responsible for association and characterise the functional significance of dimerisation. The project will further explore associations between UGTs and other proteins, namely albumin. Characterisation of UGT dimerisation and associations with other proteins is fundamental to our understanding of how this enzyme functions and selects particular chemicals for metabolism. The work also has important implications for the devlopment and interpretation of in vitro (or 'test-tube') approaches for predicting how drugs are metabolised in humans. Such tests are widely employed in research and pharmaceutical company laboratories to predict how the body 'handles' new drugs prior to their administration to humans.Read moreRead less