Improving Protection Against Childhood Tuberculosis: The Influence Of BCG Vaccine Strain And Age On Protective Immunity
Funder
National Health and Medical Research Council
Funding Amount
$473,739.00
Summary
BCG vaccine is of vital importance in the fight against the increasing problem of TB worldwide, particularly in children. This project will compare the 3 most commonly used different strains of BCG vaccine to determine which produces the best protective immunity in newborns. It will also determine whether BCG at birth or at 2 months of age provides better protection. Optimising the timing and strain used for BCG immunisation would prevent large numbers of cases and deaths from TB at low cost.
Enhancing The Cardioprotective Effect Of Diadenosine Tetraphosphate: Designing Inhibitors Against Ap4A Hydrolase
Funder
National Health and Medical Research Council
Funding Amount
$442,500.00
Summary
Ischemia describes the condition where blood flow in the blood vessels of the heart is decreased or blocked, preventing delivery of oxygen and nutrients to the heart. Ischemic preconditioning is a phenomenon where short bursts of ischemia, followed by reperfusion, actually protect the heart from a subsequent longer period of ischemia. The biochemical signalling events involved in preconditioning are complex and incompletely defined, but most likely involve multiple pathways, although the mitocho ....Ischemia describes the condition where blood flow in the blood vessels of the heart is decreased or blocked, preventing delivery of oxygen and nutrients to the heart. Ischemic preconditioning is a phenomenon where short bursts of ischemia, followed by reperfusion, actually protect the heart from a subsequent longer period of ischemia. The biochemical signalling events involved in preconditioning are complex and incompletely defined, but most likely involve multiple pathways, although the mitochondrial ATP-dependent potassium channel may be in common with most pathways. Pretreatment with the compound diadenosine tetraphosphate (Ap4A) mimics ischemic preconditioning with noticeable reductions in tissue necrosis (cell death). This treatment has been shown in experimental work to protect the heart during periods of stress such as in heart surgery or recovery from an ischemic event. The biological site of action by Ap4A may be the mitochondria ATP-dependent potassium channel or an associated protein. Ap4A can be degraded by enzymes located inside and on the outside of heart cells, notably by two forms of Ap4A hydrolase. We will use antibody assays to understand the specific localization and amount of Ap4A hydrolase before and after ischemia and after ischemic preconditioning in human heart muscle and blood vessels. We propose to determine the structure of the enzyme and use novel computer methods to screen databases for potential inhibitors. These inhibitors of Ap4A hydrolase activity could aid the design of a potent inhibitor that would prevent Ap4A hydrolase from degrading Ap4A and therefore enhance the cardioprotective properties of Ap4A as well as minimizing side effects from the break down of Ap4A. We will also use these inhibitors and other known non-degradable Ap4A analogues in bioassays to test the relative significance of Ap4A hydrolase present in different cellular locations.Read moreRead less
Gamma-Secretase Inhibitors As Novel Pharmacological Agents To Target Stroke-induced Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$441,511.00
Summary
Stroke is the world�s 2nd leading cause of death. In Australia, stroke is the leading cause of serious, long-term disability. Alarmingly, there is a looming stroke epidemic in Australia. There is an urgent need for novel therapies capable of reducing mortality and long-term disability in victims of stroke. We have recently identified gamma-secretase inhibitors (GSIs) as a potent stroke therapy. This project will investigate how GSIs protect against ischaemic stroke at the molecular level.
The Ability Of Sunscreens To Protect Against The Induction Of Solar Irradiation-induced Melanocytic Naevi In Vivo.
Funder
National Health and Medical Research Council
Funding Amount
$106,854.00
Summary
Melanoma is an increasing problem in Australia. Strong evidence supports the finding that the number of moles on skin is a good indicator of future melanoma risk and a short term marker of adverse reactions to melanoma-inducing sun exposure in humans. While recommendations for sun protection have been proposed for many years, it is currently unknown what component of sunlight induces melanoma or whether sunscreens protect against the formation of melanoma. Using an animal model for human moles o ....Melanoma is an increasing problem in Australia. Strong evidence supports the finding that the number of moles on skin is a good indicator of future melanoma risk and a short term marker of adverse reactions to melanoma-inducing sun exposure in humans. While recommendations for sun protection have been proposed for many years, it is currently unknown what component of sunlight induces melanoma or whether sunscreens protect against the formation of melanoma. Using an animal model for human moles of the skin we aim in contributing to the answers of these two questions .Read moreRead less
Identifying The Targets Of Protective Immunity To Malaria In Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
Malaria in pregnancy is a major cause of disease across many countries. Pregnant women have a high risk of malaria, and large numbers of malaria parasites accumulate in the placenta, which may lead to infant or maternal death. Malaria parasites infect the placenta by producing proteins that enable them to stick to the placenta. These malaria strains causing placental infection generally do not cause disease in non-pregnant individuals. Antibodies to the parasite proteins are produced in response ....Malaria in pregnancy is a major cause of disease across many countries. Pregnant women have a high risk of malaria, and large numbers of malaria parasites accumulate in the placenta, which may lead to infant or maternal death. Malaria parasites infect the placenta by producing proteins that enable them to stick to the placenta. These malaria strains causing placental infection generally do not cause disease in non-pregnant individuals. Antibodies to the parasite proteins are produced in response to placental infection, which may help control the infection and protect against further malaria in pregnancy. However, placental malaria parasites are able to vary the proteins they produce to avoid immune responses. In this project, we will study the parasite strains that cause malaria in pregnancy and the development of antibodies that protect pregnant women against malaria and its complications. We aim to identify the genes and proteins that parasites use to stick to the placenta, and determine how much variation occurs in these proteins. We will also specifically examine the role of one particular candidate gene called var2csa, and its protein, as this has been recently been associated with pregnancy malaria. We will examine how antibodies develop that recognise different proteins and different forms of malaria parasites, and determine the type of antibodies that protect pregnant women taking part in a longitudinal study of malaria in pregnancy in Malawi, Africa. We will also examine how antimalarial drugs taken in pregnancy influence the development of protective antibodies. Through these studies we aim to understand how the immune system combats malaria in pregnancy. This will be important for developing new methods for preventing or treating malaria in pregnancy, and improving child and maternal health.Read moreRead less