Preclinical Optimisation Of Intrauterine Transplantation Of Fetal Mesenchymal Stem Cells For Osteogenesis Imperfecta.
Funder
National Health and Medical Research Council
Funding Amount
$600,932.00
Summary
Osteogenesis imperfecta is a genetic disorder causing brittle bones and fractures. Currently there is no good treatment. Transplanting stem cells before birth should allow them to build healthy bones early in life. Despite promising effects in animals, stem cell uptake is too low to prevent all fractures and ameliorate pain and deformity. We are studying how to improve the uptake of stem cells given to the fetus and neonate, in order to develop a treatment suitable for eventual use in humans.
Development Of The Commissural Plate And Its Role In Forebrain Commissure Development
Funder
National Health and Medical Research Council
Funding Amount
$529,565.00
Summary
During development, neurons in one hemisphere of the brain connect and communicate with neurons in the opposite hemisphere. Such neural connections between the two hemispheres are called commissures, which are large bundles of axons (neural-wires) that cross the midline of the brain. There are three commissures in the forebrain: the corpus callosum, the hippocampal commissure and the anterior commissure. This wiring of the brain is essential to its proper function. When these connections don't f ....During development, neurons in one hemisphere of the brain connect and communicate with neurons in the opposite hemisphere. Such neural connections between the two hemispheres are called commissures, which are large bundles of axons (neural-wires) that cross the midline of the brain. There are three commissures in the forebrain: the corpus callosum, the hippocampal commissure and the anterior commissure. This wiring of the brain is essential to its proper function. When these connections don't form, the brain cannot integrate and process information in fundamental ways. Over 50 different human congenital disorders are associated with the malformation of one or more of these forebrain commissures. This proposal investigates the hypothesis that a midline structure, called the commissural plate (CP), regulates the development of all forebrain commissures. The CP was first described anatomically at the turn of the 20th century in a number of different species, and in humans in 1968. However, since this time, no papers have been published on the CP. Experiments in this proposal will use modern neuroanatomical techniques, particularly magnetic resonance imaging, molecular and mouse mutagenesis techniques, and axon guidance assays, to study the CP. We will test the hypothesis that there is something fundamentally unique about the CP as the midline crossing point for all commissural axons. We generate mouse mutants that disrupt only dorsal CP formation and then determine whether the subsequent development of the dorsal commissures occurs. We also perform molecular expression, and imaging analyses on human foetal brains. Our goal is to provide an understanding of what developmental events are disrupted in human congential disorders resulting in midline brain malformations and agenesis of the forebrain commissures. Understanding the basis of these disorders will lead to more accurate diagnoses and potentially their prevention through genetic counseling.Read moreRead less
Understanding The Biology Of Pregnancy To Prevent Morbidity And Mortality
Funder
National Health and Medical Research Council
Funding Amount
$422,746.00
Summary
Progress in the care of the unborn baby, and thus optimisation of life-long health, will only come with a greater understanding of the fundamental processes that underlie pregnancy. My research is aimed at saving babies lives and reducing the long-term burdens (health, emotional and economic) of major perinatal conditions. I am uniquely placed to carry out this research, using the research tools I have developed to deliver real outcomes that will change clinical practice
Identifying Strategies To Improve Perinatal Outcomes After Assisted Conception
Funder
National Health and Medical Research Council
Funding Amount
$724,799.00
Summary
Around 20% of young women express concern with being able to conceive, 16% experience clinical infertility, and ~8% use invasive therapies for which there can be limited safety data. We, and others, have reported adverse events for mother and child after infertility treatment, including neonatal death and birth defects. This project will provide urgently needed, robust evidence to guide patient and clinical decision making so as to optimise health of mother and baby.
I am a developmental lung physiologist who specialises in understanding the factors regulating normal and abnormal lung development as well as the physiological transformation of the lung into an efficient gas-exchange organ at birth.
Birth is one of the greatest physiological challenges that we will ever experience and so it is not surprising that it is a period of high risk of death. Despite the risk, our understanding of how infants transition from fetal to newborn life is limited. My research is focused on improving our understanding of how infants make the transition at birth so that we can reduce the risks for these most vulnerable of humans. In particular, I want to improve outcomes for infants born very premature.
Improving The Neonatal Transition In Infants With A Congenital Diaphragmatic Hernia
Funder
National Health and Medical Research Council
Funding Amount
$551,644.00
Summary
Congenital diaphragmatic hernia is a common congenital abnormality and occurs when the diaphragm fails to separate the abdominal and thoracic compartments before birth. This prevents the lung from growing properly and so at birth, the lung is unable to take over the role of gas exchange without considerable assistance. As a result, these infants are at high risk of death or significant disability and this application is focused on improving care and reducing morbidity in these infants.
Facilitating The Increase In Pulmonary Blood Flow At Birth
Funder
National Health and Medical Research Council
Funding Amount
$617,729.00
Summary
Pulmonary hypertension in newborn infants is a significant problem that is very difficult to treat because we do not understand how blood flow through the lungs increases at birth. We have recently shown that currently believed mechanisms controlling blood flow at birth are incorrect and additional factors exist. Our experiments will determine factors that affect blood flow through the lungs at birth. This information will be used to improve the care of newborns with pulmonary hypertension.
Carbon Dioxide As A Treatment For Seizures In The Newborn
Funder
National Health and Medical Research Council
Funding Amount
$878,389.00
Summary
This study aims to introduce a simple and effective treatment to prevent brain damage from seizures in babies using CO2. Neonatal seizures remain a major clinical problem worldwide and are associated with poor brain outcomes and significant risk of death. Recent trials in human adult epileptics show rapid and effective seizure suppression following the use of CO2. This therapy will significantly impact long-term outcomes for affected babies and reduce the burden of care for families and society.
An Integrated Approach To Inotropic Support In Preterm Neonates
Funder
National Health and Medical Research Council
Funding Amount
$694,449.00
Summary
Poor cardiovascular function in preterm babies can lead to inadequate blood flow to the brain and brain injury. Current treatments to improve heart function are often ineffective. This study will examine the effects of treatment on different parts of the cardiovascular system, and how these effects interact. It will identify reasons for the lack of effectiveness and provide insight which will help to design better treatments for preterm babies.