Characterisation Of Immune Regulators In The Human Myometrium.
Funder
National Health and Medical Research Council
Funding Amount
$85,285.00
Summary
Premature birth is a major cause of perinatal death and morbidity. It further predisposes the individual to increased morbidity throughout life. Although the mechanism of birth has been heavily researched with an objective of preventing preterm babies, it is still not fully understood. A major problem has been the lack of suitable and accessible animal models. A key organ coordinating the birth event is the uterine smooth muscle, myometrium. For effective birth and delivery, the myometrium needs ....Premature birth is a major cause of perinatal death and morbidity. It further predisposes the individual to increased morbidity throughout life. Although the mechanism of birth has been heavily researched with an objective of preventing preterm babies, it is still not fully understood. A major problem has been the lack of suitable and accessible animal models. A key organ coordinating the birth event is the uterine smooth muscle, myometrium. For effective birth and delivery, the myometrium needs to be contracting synchronously in a coordinated manner to dilate the cervix while pushing the fetus into position for eventual delivery through the birth canal. This project aims to characterise the molecular events occurring at the myometrium which precedes and precipitates labour. These local changes will be linked with the systemic hormonal changes in order to approach a model for human parturition.Read moreRead less
Molecular Mechanisms Regulating Spontaneous Onset Of Human Labour
Funder
National Health and Medical Research Council
Funding Amount
$481,156.00
Summary
The single most important complication contributing to poor pregnancy and neonatal outcome is premature birth. If we are to provide the best possible start to life, improve perinatal health and reduce the risk of developing adult disease . A better understanding of labour is requisite to improving health care delivery during pregnancy and outcomes for both mother and baby. This reserach project will investigate the how labour-associated events are reguluated by nuclear proteins.
This project will test if the ratio of the two different estrogens found in the blood of pregnant women is the critical factor in determining the onset of contractions in the uterus at labour. The studies will also determine the role of a newly discovered receptor for estrogens in allowing powerful contractions at labour. Results will allow development of new treatments to prevent premature birth that block the actions of estrogen at this new receptor or change the ratio of the two estrogens.
Regulation Of Progesterone Action In Human Parturition.
Funder
National Health and Medical Research Council
Funding Amount
$314,983.00
Summary
Premature birth is the leading cause of neonatal death and sickness, and numbers are increasing due to our ignorance of the biology of labour. Progesterone maintains pregnancy and its withdrawal results in birth, but how this is achieved in humans is unknown. This project will determine the molecular mechanisms by which progesterone action is regulated during the transition from pregnancy to birth. This data will guide new strategies to prevent premature birth.
The Mechanisms That Regulate The Onset Of Human Labour And Delivery
Funder
National Health and Medical Research Council
Funding Amount
$528,170.00
Summary
Reproductive biologists still cannot explain the molecular mechanisms that govern human birth. This lack of knowledge prevents the development of better moitoring and treament of complications of labour and delivery. If we are to provide the best possible start to life and improve newborn health care delivery then we must: (1) better understand what triggers labour; (2) determine whether there are biomarkers that we can use to identify women at risk of early birth; and (3) identify new ways to d ....Reproductive biologists still cannot explain the molecular mechanisms that govern human birth. This lack of knowledge prevents the development of better moitoring and treament of complications of labour and delivery. If we are to provide the best possible start to life and improve newborn health care delivery then we must: (1) better understand what triggers labour; (2) determine whether there are biomarkers that we can use to identify women at risk of early birth; and (3) identify new ways to delay birth. This is the overall objective of this research project. In particular, this project focuses on how the multiple events needed to achieve a successful outcome to pregnancy are coordinated at the time of birth.Read moreRead less
A Comprehensive Analysis Of Myb Target Genes Involved In Myelopoiesis And Myeloid Transformation
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
The MYB gene is essential for both normal blood cell formation and the growth of leukaemia cells. It acts by switching other genes (target genes) on and off. This project aims to advance our understanding of how MYB functions, by carrying out a comprehensive search for MYB target genes. In particular it will focus on target genes that help explain MYB's ability to control cellular growth and maturation. Some of these target genes may provide leads for future anti-cancer drug development.
Development And Validation Of A Finite Element Model For Orthopaedic Screw Insertion Into Trabecular Bone
Funder
National Health and Medical Research Council
Funding Amount
$420,454.00
Summary
Osteoporosis is a disease of the bones that results in reduced bone strength and susceptibility to fragility fractures. Due to the spongy nature of osteoporotic bone, surgeons face major difficulties in obtaining secure fixation of bone screws. Our aim is to develop and validate a computer model of orthopaedic screw insertion into trabecular bone based on micro-computed tomography image data. This will allow an assessment of the most appropriate screw designs for stable fixation of implants.
Rhythmicity And Synchronicity In Uterine Smooth Muscle
Funder
National Health and Medical Research Council
Funding Amount
$291,823.00
Summary
Natural birth occurs through rhythmic contractions of the smooth muscle of the uterus. There is surprisingly little understanding of the mechanism of the pacemaker clock that both initiates and times each contraction in a coordinated manner to expel the fetus. This project is to challenge this knowledge gap using our findings on cellular rhythms that herald Ca2+ stores as a major pacemaker mechanism. First, we will use electrophysiology and calcium imaging techniques to test the hypothesis that ....Natural birth occurs through rhythmic contractions of the smooth muscle of the uterus. There is surprisingly little understanding of the mechanism of the pacemaker clock that both initiates and times each contraction in a coordinated manner to expel the fetus. This project is to challenge this knowledge gap using our findings on cellular rhythms that herald Ca2+ stores as a major pacemaker mechanism. First, we will use electrophysiology and calcium imaging techniques to test the hypothesis that rhythmicity and synchronicity of uterine contractions are underpinned by store pacemaking. Second, we will probe the role of current spread between cells via gap junctions as a mechanism of recruitment and will examine whether accessory cells termed interstitial cells subserve a role in pacemaking. These cells are present within the uterine wall but their function is unknown. We will probe their ion channel properties in relation to pacemaking using patch clamp techniques. Third, we will examine the role of labour hormones, such as oxytocin, in augmenting uterine contractions via interaction with the Ca2+ store mechanism and cell recruitment. These studies will provide new and fundamental insights into uterine pacemaking, an outcome that should be of great significance to understanding and better controlling birth-associated complications such as preterm delivery and failure to progress.Read moreRead less