Placental Malaria, Placental Function, Nutrient Transport And Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$483,517.00
Summary
Malaria infection in the placenta impairs the baby's growth, probably by causing placental inflammation. We believe this inflammation interferes with the ability of placental cells to transport nutrients such as amino acids and glucose from mother to baby. We will test this by examining the expression of genes and proteins involved in nutrient transport in placental samples from pregnant women, and in cell lines, and will examine how malaria affects growth factors that control this process.
Trafficking Of The Major Virulence Protein To The Host Cell Surface In Malaria Parasite-infected Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$658,164.00
Summary
The malaria parasite infects human red blood cells and causes them to stick to blood vessels in the brain, inducing coma. This causes the deaths of ~2 million children each year. We will use cell biology techniques to manipulate malaria parasites to unravel the details of the molecular ticketing system that the parasite uses to get its adhesive proteins onto the red blood cell surface. The ability to interfere with this process would greatly decrease the impact of this major human pathogen.
Trafficking Of The Cytoadherence-mediating Protein To The Host Cell Surface In Malaria Parasite-infected Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$547,315.00
Summary
Malaria kills between 1 and 3 million children each year. In addition, the disease debilitates the adult population in malaria-endemic areas, thereby contributing to the cycle of poverty in many third world countries. As resistance to existing antimalarial drugs increases, there is an urgent need to understand the workings of the parasite at a molecular level to enable the development of alternative antimalarial strategies. During part of its life cycle, the malaria parasite infects the red bloo ....Malaria kills between 1 and 3 million children each year. In addition, the disease debilitates the adult population in malaria-endemic areas, thereby contributing to the cycle of poverty in many third world countries. As resistance to existing antimalarial drugs increases, there is an urgent need to understand the workings of the parasite at a molecular level to enable the development of alternative antimalarial strategies. During part of its life cycle, the malaria parasite infects the red blood cells of its human host. The parasite transports proteins to the red blood cell membrane so as to modify the properties of its adopted cellular residence. The parasite proteins that are deposited at or in the red blood cell membrane increase the leakiness and the stickiness of the parasitised red blood cells. This allows more efficient uptake of nutrients and allows the parasitised red blood cells to adhere to blood vessel walls, thereby avoiding passage through the spleen. Adherence of parasitised red blood cells to capillaries in the brain and the placenta is thought to lead to the development of the complications known as 'cerebral' and 'placental' malaria. These complications are responsible for the deaths of many children and pregnant women. We propose to use cell biology techniques to introduce foreign genes into malaria parasite-infected red blood cells to unravel the details of the molecular machinery and the ticketing system that the parasite uses to traffic its virulence proteins to their correct destinations. These studies could potentially lead to the development of novel intervention strategies. For example, if it were possible to decrease the levels of surface expression of a protein known as PfEMP1, adhesion of infected red blood cells would be inhibited. This would greatly decrease the impact of this important human pathogen.Read moreRead less
Developing Molecularly Targeted Therapeutics And Diagnostics For Pregnancy Complications
Funder
National Health and Medical Research Council
Funding Amount
$321,489.00
Summary
Pregnancy complications still causes the death of mothers, and their babies. During this fellowship, we will be developing new treatments and clinical tests for three important complications of pregnancy. We will run clinical trials of a new medication based treatment to cure ectopic pregnancies. We will also develop a blood test that can identify those babies still in the womb but suffering dangerously low oxygen levels. Lastly, we will develop drugs to treat preeclampsia, a serious condition o ....Pregnancy complications still causes the death of mothers, and their babies. During this fellowship, we will be developing new treatments and clinical tests for three important complications of pregnancy. We will run clinical trials of a new medication based treatment to cure ectopic pregnancies. We will also develop a blood test that can identify those babies still in the womb but suffering dangerously low oxygen levels. Lastly, we will develop drugs to treat preeclampsia, a serious condition of pregnancy.Read moreRead less
The Impact Of Severe Asthma During Pregnancy On Placental Function And Fetal Hypothalamic-pituitary-adrenal Function
Funder
National Health and Medical Research Council
Funding Amount
$209,242.00
Summary
This study will examine whether the glucocorticoids administered for the control of severe asthma during pregnancy affects placental and fetal function. It is known that severe asthma during pregnancy is associated with low birth weight babies but the events that cause reduced growth of the baby are unknown. However in both animal and human pregnancies, increased exposure of the baby to glucocorticoids from the mother causes growth restriction of the baby. Therefore we propose that the increased ....This study will examine whether the glucocorticoids administered for the control of severe asthma during pregnancy affects placental and fetal function. It is known that severe asthma during pregnancy is associated with low birth weight babies but the events that cause reduced growth of the baby are unknown. However in both animal and human pregnancies, increased exposure of the baby to glucocorticoids from the mother causes growth restriction of the baby. Therefore we propose that the increased intake of glucocorticoids for the treatment of asthma during pregnancy changes how the placenta functions and allows the fetus to be exposed to maternal glucocorticoids causing changes in fetal development. We will examine placental blood flow and measure some placental enzymes that may be involved in the control of blood flow in placentas collected from women with mild, moderate and severe asthma and compare them to non-asthmatic women. We will look at placental blood flow in utero using Doppler ultrasound and also in vitro after the placenta is delivered. We want to see if the fetus is affected by increased intake of glucocorticoids by the mother by measuring a hormone estriol, which originates from the fetus. We will measure estriol throughout pregnancy as it can easily be detected in the mothers' urine. These studies will tell us if glucocorticoid intake for the treatment of asthma can exert effects on the placenta and baby during pregnancy. These studies will make a significant contribution both scientifically and clinically. At a scientific level we will be able to examine how increased maternal glucocorticoid intake during pregnancy affects placental mechanisms and whether these changes affect the fetus and clinically the outcome of this study will allow us to optimize asthma therapy during pregnancy so that we can improve the outcome for the baby.Read moreRead less
Disease Burden, Risk Factors And Treatment Of Knowlesi Malaria
Funder
National Health and Medical Research Council
Funding Amount
$95,564.00
Summary
Plasmodium knowlesi is a form of monkey malaria recently found to also cause increasing numbers of natural infections in humans in South-East Asia. This research will describe the burden of P. knowlesi malaria in an area of Malaysian Borneo. The risk factors for acquiring P. knowlesi malaria will be assessed. Finally the optimal treatment for non-severe cases of P. knowlesi and P. vivax malaria will also be evaluated by comparing the 2 currently recommended anti-malarial medications in Malaysia.
Functional Resolution Of PTEX, The Exporter Of Virulence Factors In Malaria Parasites.
Funder
National Health and Medical Research Council
Funding Amount
$625,212.00
Summary
Almost half a million people die each year of malaria and nearly half the world’s population are at risk. To eliminate malaria this century we will need new drugs and vaccine to fight the disease. One potential drug target are the molecular gateways called PTEX, that are used by parasites to export virulence proteins into their human host cells. This grant aims to understand how the PTEX molecular machines work so we can develop new drugs to block them and kill the parasites.
Developing A Screening Test To Identify Women At Risk Of Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$1,119,284.00
Summary
Preeclampsia is a serious complication of pregnancy for which there is currently no cure and no way to accurately predict women at risk. Using large collections of human blood samples, we will screen for novel proteins within pregnant women's blood. We will then use artificial intelligence to select the best biomarkers and combine them with clinical information to develop a multi-marker blood test to predict women at risk.
The transmission of malaria is dependent on gametocytes, the sexual stages of parasite development that are taken up by mosquitoes when feeding on an infected person. While gametocytes are not responsible for disease symptoms, it is clear that malaria eradication is not be possible without an understanding of their biology and the tools to prevent transmission. My research focuses on understanding the biology of gametocytes and identifying new drug targets for transmission blocking strategies.