Mechanisms Underlying APOBEC3G Restriction Of HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
In the fight against worldwide HIV-AIDS, understanding natural cell defenses to the HIV virus may identify new virus targets and strategies to block HIV in humans. Here, we will use state-of-the-art, high resolution, fluorescent microscopy to understand how the recently identified cell protein, APOBEC3G, blocks the HIV life cycle in human cells. We anticipate that APOBEC3G will stop HIV from invading the nucleus of human cells to defend against HIV, a strategy we can apply to new therapies.
Antenatal Insulin-like Growth Factor-I And Perinatal Growth, Survival And Function Of The Growth Restricted Fetus.
Funder
National Health and Medical Research Council
Funding Amount
$150,370.00
Summary
Poor growth before birth or intrauterine growth restriction (IUGR), as indicated by being light, short or thin for stage of pregnancy, greatly increases the risk of illness and death before and after birth and in infancy. IUGR has increased risks of asphyxia, poor glucose control, hypothermia, respiratory difficulties, neurological problems and poor immune function, many of which persist. IUGR is one of the most common clinical problems in obstetrics and neonatology, with ~6% of infants born IUG ....Poor growth before birth or intrauterine growth restriction (IUGR), as indicated by being light, short or thin for stage of pregnancy, greatly increases the risk of illness and death before and after birth and in infancy. IUGR has increased risks of asphyxia, poor glucose control, hypothermia, respiratory difficulties, neurological problems and poor immune function, many of which persist. IUGR is one of the most common clinical problems in obstetrics and neonatology, with ~6% of infants born IUGR in Australia in non-Aboriginal communities and between 7 to 17% in Aboriginal communities. Despite these adverse consequences for health of the individual throughout life, we do not currently have any effective therapies to treat IUGR. Small infants are mostly a result of an inadequate supply of oxygen and nutrients before birth, due to an impaired capacity of the mother to acquire these for the placenta to deliver them to the growing fetus or due to poor functioning of the placenta itself. This intrauterine malnutrition not only slows growth, but impairs the development of a range of body functions leading to the increased risk of illness and death in IUGR. Therapies to be used before birth to treat IUGR need to either restore supply of oxygen and nutrients or to promote growth and functional development. We have discovered that administration of a major growth promoting hormone, insulin-like growth factor-I (IGF-I), to the IUGR fetus, which has low levels of IGF-I, increases its growth. This project will therefore determine if directly giving this hormone in the IUGR fetus will restore development as well as growth before birth, improving function and hence survival and health after birth. If successful, the first effective approach to the antenatal treatment of IUGR will have been identified and would provide the essential knowledge for the design of a range of therapies to best restore the abundance of IGF within the IUGR fetus to improve perinatal and later outcomes.Read moreRead less
Insulin-like Growth Factor (IGF) -II, Cytotrophoblast Migration And Placental Development
Funder
National Health and Medical Research Council
Funding Amount
$487,750.00
Summary
During pregnancy, placental cells invade into the uterus and tap into the maternal blood vessels to procure an adequate blood supply for the growth of the placenta and hence the fetus. If this invasion process is impaired early in pregnancy, then the woman may suffer a miscarriage, if the process is impaired in mid-pregnancy then the mother may develop preeclampsia in which her blood pressure goes up and, in severe cases, placing her life and that of her unborn baby at risk. Miscarriage occurs i ....During pregnancy, placental cells invade into the uterus and tap into the maternal blood vessels to procure an adequate blood supply for the growth of the placenta and hence the fetus. If this invasion process is impaired early in pregnancy, then the woman may suffer a miscarriage, if the process is impaired in mid-pregnancy then the mother may develop preeclampsia in which her blood pressure goes up and, in severe cases, placing her life and that of her unborn baby at risk. Miscarriage occurs in 10-15% of pregnancies and preecclampsia in 7% of pregnancies. Preecclampsia may be life-threatening in up to 3% of all pregnancies and is a major cause of maternal death in pregnant women in Western countries. This project will examine the effect of treatment of the pregnant guinea pig with insulin-like growth factor-II on placental cell invasion and the capacity of the placenta to deliver nutrients to the fetus. We will also determine whether the effects of this treatment are mediated by a specific membrane receptor on the cell surface of the invading placental cells. We predict that this growth factor will enhance placental cell invasion and improve placental function. If this is the case then our findings may be developed for use in women at risk, to improve placental function and hence maternal and fetal health.Read moreRead less
Diagnostic Tests To Predict Risk For Life Threatening Pregnancy Complications
Funder
National Health and Medical Research Council
Funding Amount
$682,824.00
Summary
The main complications of pregnancy, preeclampsia, preterm birth and intrauterine growth restriction afflict 19% of first pregnancies and are life threatening to the mother or baby in 6% of pregnancies. Currently we have no way of knowing which women will suffer these diseases until symptoms manifest. We aim to develop genetic tests that can predict which women are at risk. This will permit earlier interventions that will improve the health of pregnant women and their babies.
The main complications of pregnancy, preeclampsia, preterm birth and intrauterine growth restriction affliict 19% of first pregnancies and are life threatening to the mother or baby in 6% of pregnancies. They are associated with poor placental invasion of the uterus. We aim to further elucidate the molecular mechanisms involved in placental invasion and proper placental development to identify possible targets for future treatments to improve the health of pregnant women and babies.
Contribution Of Systemic Inflammatory Response To Brain Injury In Growth Restricted Newborns
Funder
National Health and Medical Research Council
Funding Amount
$363,388.00
Summary
Growth restriction during pregnancy can damage the baby’s brain and result in poor outcomes such as learning and attention difficulties and cerebral palsy. Currently there is no treatment available to prevent brain injury in these babies. This study will explore the role of inflammation and brain injury in the growth restricted baby. We will also examine whether a readily available and safe anti-inflammatory treatment can reduce or prevent brain injury following growth restriction.
Fetal Cardiovascular Development And The Impact Of Chronic Hypoxia And Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$307,232.00
Summary
Low birth weight occurs in 7% of Australian babies and is associated with an increased risk of cardiovascular disease in adult life. Understanding the mechanisms underlying heart and blood vessel development in low birth weight babies will lead to improved identification and intervention in those individuals at risk of cardiovascular disease in adult life, improving heart health for Australians. Reducing cardiovascular disease will improve both quality and quantity of life for Australians.
Pathways Of Neurosteroid-mediated Protection Following Compromised Pregnancy And Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$565,785.00
Summary
The hormonal environment of pregnancy is essential for normal development of the fetal brain. Levels of key hormones fall following premature birth and are further suppressed if the fetus is small or subjected to stress. This leads developmental problems in infants from the pregnancies. This project will examine effectiveness of replacement and supplementation treatments with critical neurosteroid hormones in reversing the adverse neurological effects of these complications of pregnancy.