The Role Of The Mammalian Grainyhead-like Gene Family In Neural Tube Closure
Funder
National Health and Medical Research Council
Funding Amount
$635,547.00
Summary
Failure of the skin to close over the brain and spinal cord during human development results in the devastating congenital birth defects anencephaly and spina bifida, known collectively as the neural tube defects. These are the second most common congenital birth defects affecting 1:1000 pregnancies. Our laboratories have identified a family of genes essential for the closure of the neural tube in mammals. The aim of this proposal is to understand the mechanisms of action of these genes with a v ....Failure of the skin to close over the brain and spinal cord during human development results in the devastating congenital birth defects anencephaly and spina bifida, known collectively as the neural tube defects. These are the second most common congenital birth defects affecting 1:1000 pregnancies. Our laboratories have identified a family of genes essential for the closure of the neural tube in mammals. The aim of this proposal is to understand the mechanisms of action of these genes with a view to developing new preventative therapeutics.Read moreRead less
STK9, A Second Rett Syndrome Gene: Genetic And Functional Studies
Funder
National Health and Medical Research Council
Funding Amount
$468,750.00
Summary
Rett syndrome (RTT) is a devastating progressive disorder affecting motor and intellectual development. It is characterised by normal development for the first 6-12 months of life, followed by developmental regression with the loss of learned purposeful hand function, loss of acquired speech and communicative abilities, sometimes leading to the incorrect diagnosis of autism. It may be the most common cause of progressive mental retardation in girls, with an estimated prevalence in Australia of 1 ....Rett syndrome (RTT) is a devastating progressive disorder affecting motor and intellectual development. It is characterised by normal development for the first 6-12 months of life, followed by developmental regression with the loss of learned purposeful hand function, loss of acquired speech and communicative abilities, sometimes leading to the incorrect diagnosis of autism. It may be the most common cause of progressive mental retardation in girls, with an estimated prevalence in Australia of 1 per 10,000 females under the age of twelve years. It is a genetic disorder and occurs almost exclusively in females. In 1999, a gene (called MECP2) was identified which appears to be the cause of RTT in most girls and women with RTT. However, for 5 - 10% of RTT subjects, no gene change is found in the MECP2 gene, raising the possibility that other genes may also be responsible for RTT. Our research group has identified one of these genes. Known as STK9, little is known about this gene's function. Of great interest is the fact that our studies suggest that STK9 could also be a caus of intellectual disability in other patients, and with autism. The focus of this research project is to explore how common gene changes in STK9 are in a large number of children with RTT, intellectual disability and seizures, and autism with intellectual disability and seizures. Using cutting edge research technology, we will go on to study how STK9 interacts with MECP2 and other genes, in order to better understand how these genes may be detrimentally affecting brain function in girls and women with Rett syndrome and other neurological disorders. These studies will give us a greater understanding of normal brain development and function.Read moreRead less
A common medical problem is the inability to maintain normal blood pressure while standing. This can cause blackouts, falls and injury. The available medical treatment is very deficient, because the various body mechanisms at play are poorly understood, so it has not been possible to specifically target the root cause. This grant application aims to study patients with these “postural hypotension” disorders, to better understand how the problems develop, and consequently, to provide better medic ....A common medical problem is the inability to maintain normal blood pressure while standing. This can cause blackouts, falls and injury. The available medical treatment is very deficient, because the various body mechanisms at play are poorly understood, so it has not been possible to specifically target the root cause. This grant application aims to study patients with these “postural hypotension” disorders, to better understand how the problems develop, and consequently, to provide better medical treatment.Read moreRead less
Function Of The Lysophospholipid Receptor Family In Neuronal Stem Cells And Their Progenitors.
Funder
National Health and Medical Research Council
Funding Amount
$380,723.00
Summary
Stem cells have the potential to give rise to a vast array of differentiated cells. Neuronal stem cells (NSC) can differentiate into progenitor cells which can themselves differentiate into cells of the nervous system: neurons and macroglial cells (astrocytes, oligodendrocytes, Schwann cells). This in turn can assist in the treatment of degenerative diseases such as multiple sclerosis, Parkinson's disease, motoneuron desease etc. Our project aims to study the effects on NSC and their progenitor ....Stem cells have the potential to give rise to a vast array of differentiated cells. Neuronal stem cells (NSC) can differentiate into progenitor cells which can themselves differentiate into cells of the nervous system: neurons and macroglial cells (astrocytes, oligodendrocytes, Schwann cells). This in turn can assist in the treatment of degenerative diseases such as multiple sclerosis, Parkinson's disease, motoneuron desease etc. Our project aims to study the effects on NSC and their progenitor cells of the lysophospholipids lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P), bioactive molecules known to play an essential role in the nervous system during development and inflammation. Our project aims to understand the mechanisms of action of these molecules in NSC maintenance, proliferation, differentiation and migration. By understanding how these molecules are able to regulate NSC biology will provide new avenues in the development of tools necessary for stem cell therapy.Read moreRead less
The Role Of The Zinc Finger Transcriptional Repressor Znf238 During Nerve Cell Maturation
Funder
National Health and Medical Research Council
Funding Amount
$394,264.00
Summary
Proper foetal brain assembly is critical for brain function, but the underlying genetic mechanisms remain poorly defined. In this study, I will investigate a family of proteins that “turn on” neural gene expression in combination with another protein that “turns off” their expression during nerve cell development. Understanding this novel on/off mechanism for controlling gene expression in newborn nerve cells will further our understanding of how the brain is assembled.
Regulation Of Extraocular Myosins In Craniofacial Muscles
Funder
National Health and Medical Research Council
Funding Amount
$196,018.00
Summary
Muscles which move the eyeball are highly complex and contain a special motor protein which enables them to contract with the highest speed of all muscles in the body. This protein is found also in muscles of the throat which open and close the airway during coughing, sneezing and swallowing. These muscles also make many other types of motor proteins, giving them a wide spectrum of properties. The functional advantage of having very fast muscles to move the eyes, and protect the airway by preven ....Muscles which move the eyeball are highly complex and contain a special motor protein which enables them to contract with the highest speed of all muscles in the body. This protein is found also in muscles of the throat which open and close the airway during coughing, sneezing and swallowing. These muscles also make many other types of motor proteins, giving them a wide spectrum of properties. The functional advantage of having very fast muscles to move the eyes, and protect the airway by preventing foreign bodies from entering the lungs, is obvious, but how the synthesis of this motor protein is restricted to these muscles is intriguing. Studies in limb muscles have established the principle that the type of motor protein in a muscle is determined by both the type of muscle cells and the type of innervation. Nerves can change the motor proteins in response to the pattern of use imposed by the brain via electrical impulses along its nerve supply. It is known that frequency of nerve impulses to eye muscles are exceptionally high. This project will use several approaches to test the hypothesis that the nerve impulse pattern delivered to these special muscles is involved in the regulation of this motor protein. In one approach, these muscles in rat will be subject to long-term paralysis by cutting their nerve or by the use of botulinum toxin to see if the motor protein is abolished or reduced. In another, the nerve to throat muscles which make this protein will be redirected to another throat muscle which does not normally make this motor protein. These experiments are expected to support the notion that eye and throat muscles are different from all other muscles in the body, and that the normal neural activity from nerves innervating these special muscles is necessary for inducing the synthesis of their motor proteins. These results will greatly help us understand how eye and throat muscles acquire their unique characteristics.Read moreRead less
The Functional Organisation And Signals Of Motion Sensitive Neurons In The Middle-temporal Area Of Visual Cortex
Funder
National Health and Medical Research Council
Funding Amount
$405,337.00
Summary
Some nerve cells in the cerebral cortex are very sensitive to visual motion. These neurons direct eye movements and provide motion perception, but the "neuronal code" they carry is poorly understood. We will address this basic question in experimental studies of the primate visual system. This project will help us understand visual performance; poor motion vision is an early indicator of many neurological disorders and this knowledge can help develop methods for their detection and diagnosis.