Obesity ensues when calorie intake exceeds energy expended. Hitherto, up-regulating energy expenditure is a relatively unexplored avenue. This project will address 3 facets of energy expenditure (fat, muscle and neural control). Understanding how sex and steroids act in concert to regulate energy expenditure will pave the way towards developing novel anti-obesity agents. This work will delineate mechanisms that underpin gender differences in the regulation of body weight.
Characterisation Of SRY Macromolecular Complexes To Provide An Enhanced Understanding Of Human Genetic Sex Reversal And Embryonic Sex Determination
Funder
National Health and Medical Research Council
Funding Amount
$237,360.00
Summary
SRY is the most important gene in the determination of human sex. Mutations in the SRY gene that disrupt its ability to interact with other cellular proteins that regulate its function have shown to result in genetic sex reversal. This project will provide a detailed structural profile of the interfaces that are critical for sex determination, provide a molecular basis for XY-genetic sex reversal, and an enhanced understanding of foetal development.
Making Human T- And B-lymphocytes For Immunotherapy And Antibody Production
Funder
National Health and Medical Research Council
Funding Amount
$795,880.00
Summary
Lymphocytes are white blood cells that are involved in producing antibodies, killing defective cells, or killing cells infected with viruses. In recent years, researchers have found ways to harness lymphocytes to develop medicines for treating a variety of different cancers. In this project, we will establish methods to make human lymphocytes in the laboratory from stem cells, paving the way for the broader application of this cell type to new therapies.
Deciphering The Epigenetic Code Of T Lymphocyte Stability In Disease
Funder
National Health and Medical Research Council
Funding Amount
$662,785.00
Summary
T lymphocytes defend against invading pathogens and establish immunological memory to protect us if the infection returns. As there are many different types of pathogens, T lymphocytes must be flexible in the way they respond to infection but also stable once they have decided on the appropriate type of response. This complex decision-making appears to be dictated by epigenetic changes to the chromatin state of the cell. This work will uncover epigenetic factors that maintain this balance to pro ....T lymphocytes defend against invading pathogens and establish immunological memory to protect us if the infection returns. As there are many different types of pathogens, T lymphocytes must be flexible in the way they respond to infection but also stable once they have decided on the appropriate type of response. This complex decision-making appears to be dictated by epigenetic changes to the chromatin state of the cell. This work will uncover epigenetic factors that maintain this balance to protect us against disease.Read moreRead less
SULT4A1 is not a sulfotransferase, but a sulfotransferase inhibitor. It forms high affinity heterodimers with other sulfotransferases via a conserved dimerisation site in its carboxyl terminus attenuating catalytic activity. Consequently, it is important for the metabolism of numerous important molecules including estrogens, thyroid hormones, neurotransmitters and many therapeutic agents.
Fetal Sex: An Important Determinant Of The Placental Transcriptome
Funder
National Health and Medical Research Council
Funding Amount
$553,574.00
Summary
There are fetal sex differences in pregnancy outcomes that place boys at greater risk than girls. These are likely caused by genetic differences in the placenta. We will use 21st century gene sequencing technology to obtain the complete sequence of placental genes in early pregnancy and normal term placenta to determine what the genetic differences are between male and female placentas. This may be important in developing future sex specific therapeutics for babies in the neonatal nursery.
Do Sex Hormones Slow Biological Ageing To Improve Health Outcomes In Men?
Funder
National Health and Medical Research Council
Funding Amount
$249,569.00
Summary
As the Australian population ages their burden of ill-health increases. Our earlier research showed that higher sex hormone levels are associated with better health outcomes in older men. In this project, we will address the question whether exposure to higher sex hormone levels slows biological ageing in men, reflected in the presence of longer chromosomal ends called telomeres. If so, interventions that raise hormone levels could be tested to preserve health in ageing men.
Epigenetic Regulation Of Cell Lineage Differentiation In The Early Embryo
Funder
National Health and Medical Research Council
Funding Amount
$440,983.00
Summary
Exposure of embryos to a range of stresses can increase the predisposition to chronic diseases of adulthood. Stressing embryos at critical stages of development cause errors in reorganization of the nucleus that are required for normal gene expression. These errors are propagated into adulthood. This project will map the normal processes of nuclear reorganization and define how stress to the embryo changes this process, allowing an understanding of the causes of some important chronic diseases.
IL21, B-cell Proliferation And The Mechanism Of Memory Formation
Funder
National Health and Medical Research Council
Funding Amount
$981,896.00
Summary
Our immune system can ‘remember’ old infections, which is why we do not suffer from the same pathogen multiple times and why vaccines work. Much of this protection is due to memory B-cells, of which there are different kinds. We think the different memory B-cell subsets have different functions and understanding how they are made and how this is controlled will help us improve responses to critical infections – HIV, Flu – and in critical patient groups – aged people and transplant recipients.
Overcoming The Differentiation Block In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$811,669.00
Summary
Acute myeloid leukaemia (AML) is an aggressive leukaemia with poor overall survival. About 50% of AML cases have genetic mutations that disable PU.1, which in turn alters the expression of many other genes that cause leukaemia. We have developed new AML models allowing reversible inhibition of PU.1, and have shown that re-engaging PU.1 function causes AML regression. This project aims to understand PU.1 functions in AML and identify rational drug targets for treatment-resistant disease.