Effects Of The Histone Acetyltransferases MOZ And QKF On Chromatin Modifications
Funder
National Health and Medical Research Council
Funding Amount
$349,576.00
Summary
Cancer of the blood (leukaemia) can be caused by rearrangements of the genetic material (DNA) that cause fusions between ordinarily separate proteins. Monocytic leukaemia zinc finger (MOZ) fusion proteins cause aggressive leukaemia. We have shown that MOZ associates with DNA packaged with histone proteins into chromatin, changes histones and gene activity. We will examine how MOZ and the closely related QKF protein affect the chromatin to elucidate the function of MOZ and QKF.
Hormonal Responsive Coding And Non-coding Genes In Penile Differentiation And Hypospadias
Funder
National Health and Medical Research Council
Funding Amount
$835,182.00
Summary
Hypospadias, a failure of the correct formation of the penis, is the second-most common birth defect, occurring in around 1% of boys. It causes distress to both newborn and parents, requiring surgical intervention, and is a burden of cost and is a risk to the child. Furthermore, it is frequently associated with other abnormalities. We have a novel model in which we can induce penis abnormalities and define the link between hormonal exposures and defective penis differentiation.
Targeting Of Callosal Axons To Duplicate Cortical Areas In The Contralateral Hemisphere
Funder
National Health and Medical Research Council
Funding Amount
$600,785.00
Summary
The two sides of the brain communicate via a large fibre tract called the corpus callosum. This proposal investigates how the corpus callosum is formed during embryonic and postnatal development. Specifically, we investigate how the axons that make up the corpus callosum are able to locate their precise target in the contralateral hemisphere so that the brain circuit they form will be functional. We have developed a new mouse model to discover the fundamental mechanisms regulating how the brain ....The two sides of the brain communicate via a large fibre tract called the corpus callosum. This proposal investigates how the corpus callosum is formed during embryonic and postnatal development. Specifically, we investigate how the axons that make up the corpus callosum are able to locate their precise target in the contralateral hemisphere so that the brain circuit they form will be functional. We have developed a new mouse model to discover the fundamental mechanisms regulating how the brain is wired in order to function correctly.Read moreRead less
Guidance Mechanisms Regulating The Development Of Axonal Projections From The Cingulate Cortex.
Funder
National Health and Medical Research Council
Funding Amount
$484,236.00
Summary
The corpus callosum is the largest fibre tract in the brain and connects neurons in the left and right cerebral hemispheres. A subpopulation of callosal axons arise from neurons in the cingulate cortex and are the first to cross the midline. Defects in activation or wiring of the cingulate cortex are strongly implicated in acute pain, schizophrenia and bipolar disorder. This proposal investigates how the commissural projections of the cingulate cortex become wired up during development.
Gtf2ird1 And The Molecular And Cellular Basis Of Human Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$589,160.00
Summary
Williams-Beuren Syndrome (WBS) is a genetic disease caused by a chromosomal deletion, resulting in individuals with a distinctive set of cognitive malfunctions and personality traits. WBS provides an invaluable means to identify, and potentially therapeutically modify, genes that influence human mood and behaviour. A gene we discovered, GTF2IRD1, appears to cause the most prominent behavioural features. We will characterize the role(s) that this gene plays in brain cell function.
Cellular And Molecular Regulation Of Interhemispheric Fusion
Funder
National Health and Medical Research Council
Funding Amount
$449,489.00
Summary
In the developing brain, the two cerebral hemispheres undergo interhemispheric fusion to allow commissural fibres to cross the midline. Lack of interhemispheric fusion results in agenesis of the corpus callosum and may manifest as an interhemispheric cyst in acallosal patients. This project will investigate the cellular and molecular mechanisms that regulate interhemispheric fusion, including removal of the leptomeninges, astroglial differentiation and the formation of adherens junctions at the ....In the developing brain, the two cerebral hemispheres undergo interhemispheric fusion to allow commissural fibres to cross the midline. Lack of interhemispheric fusion results in agenesis of the corpus callosum and may manifest as an interhemispheric cyst in acallosal patients. This project will investigate the cellular and molecular mechanisms that regulate interhemispheric fusion, including removal of the leptomeninges, astroglial differentiation and the formation of adherens junctions at the interhemispheric fissure to mediate fusion.Read moreRead less
Investigation Of Processed SnoRNAs As Cryptic Regulators Of The Imprinted Prader-Willi Syndrome Locus
Funder
National Health and Medical Research Council
Funding Amount
$673,976.00
Summary
Prader-Willi syndrome (PWS) is a devastating disorder whose symptoms include intellectual disability and compulsive eating. PWS occurs when a piece of the genome is mistakenly deleted, but why this DNA is important is still not understood. Our data indicate that the deleted DNA encodes a suite of previously hidden genetic elements, and here we proposed using the latest high-throughput DNA and RNA sequencing and stem cell technologies to finally unravel this mystery.
The Molecular And Biological Roles Of Growth Inhibiting Chromatin Binding Proteins
Funder
National Health and Medical Research Council
Funding Amount
$814,843.00
Summary
Our previous work has led to the identification of mutations underlying human birth defects. Similarly, our proposed work will identify a new gene as potentially mutated in human heart defects. We will determine its overlapping functions with a related gene and elucidate their roles in embryonic development and cancer.
Autism is characterised by deficits in social behaviour and communication, and is a cause of major lifelong disability. A novel intervention, oxytocin nasal spray, enhances social cognition and behaviour in humans, including in those with autism spectrum disorders. This project will determine whether oxytocin, taken twice daily over 8 weeks, improves social communication and interaction skills in toddlers with autism. This project represents a crucial step in developing an early intervention tre ....Autism is characterised by deficits in social behaviour and communication, and is a cause of major lifelong disability. A novel intervention, oxytocin nasal spray, enhances social cognition and behaviour in humans, including in those with autism spectrum disorders. This project will determine whether oxytocin, taken twice daily over 8 weeks, improves social communication and interaction skills in toddlers with autism. This project represents a crucial step in developing an early intervention treatment for autism.Read moreRead less
Endogenous Oestrogen Is A Key Missing Link In Urethral Hypospadias
Funder
National Health and Medical Research Council
Funding Amount
$456,467.00
Summary
Defects in penis development are among the most common birth abnormalities, and affect around 1 in every 150 live male births in Australia. Development of the penis is known to be driven by male hormones (androgens), but we have recently shown that oestrogen also plays a role in this process. This project will define the role of estrogen in penis development and how a loss or gain of estrogens can cause developmental defects.