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.
Analysis Of Gene Regulation In Disorders Of Sex Development
Funder
National Health and Medical Research Council
Funding Amount
$524,852.00
Summary
Disorders of Sex Development (DSD) are surprisingly common, however the majority of cases still cannot be explained. Our hypothesis is that a significant proportion of DSD is due to disturbed gene regulation. We will use state of the art methods to analyse the regulation of DSD genes. Our research will improve our knowledge of the regulation of genes that affect DSD and provide a diagnosis for DSD patients for whom the underlying cause is unknown. This in turn will improve clinical management.
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.
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.
Novel DNA Modifications Underlying Sex Differences In Fear-related Learning And Memory
Funder
National Health and Medical Research Council
Funding Amount
$531,978.00
Summary
Women are at increased risk of developing fear-related anxiety disorders. We have recently discovered that there sex-specific regulatory mechanisms in the brain that are associated with differences in the control of fear. In this proposal, we will determine whether novel DNA modifications in the female brain are responsible for establishing sex differences in brain states that make the brain more or less responsive to fear-related learning.
Local Cardiac Sex Steroids - New Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$646,994.00
Summary
The sex hormones, estrogen and testosterone, are implicated in susceptibility to heart diseases - the timing and type of disease development is different for women and men. The mechanisms for this are unknown. In this project we investigate the synthesis and breakdown of these hormones in the heart and determine how local hormone levels may affect heart muscle cell survival and function. The aim is to find ways of adjusting hormone balance to optimize protection when the heart is under stress.
Sex Hormones And Heart Disease In Older Women Study (The SHOW Study)
Funder
National Health and Medical Research Council
Funding Amount
$594,672.00
Summary
Cardiovascular disease (CVD, heart disease and stroke) is the leading cause of death in women aged 65 and over. Counter-intuitively, androgens may be as, or even more important, than estrogens in determining CVD risk and all-cause mortality in women, but this is yet to be verified. We will document blood levels of androgens in women aged 70+ and determine whether androgens are associated with CVD and death in this large cohort of elderly well women.
Sex Disparities In Management Of Myocardial Infarction
Funder
National Health and Medical Research Council
Funding Amount
$624,203.00
Summary
We propose using linked routine Big Data from the NSW health system to investigate sex differences in medications prescribed following a first MI, including deviances from guideline recommendations. We will also quantify differences between women and men in subsequent adverse outcomes, such as recurrent MI, according to treatment prescribed, and will study variations in sex dif
Y Chromosome Mechanisms In Coronary Artery Disease
Funder
National Health and Medical Research Council
Funding Amount
$369,076.00
Summary
The Y chromosome determines sex in men and until recently was not thought to contribute to heart disease. We previously found a specific type of Y chromosome that does contribute to heart disease. In the current project we plan to find the exact gene and mechanism in the search as a therapeutic target.