The Embryological And Molecular Basis Of Zic2 Involvement In Holoprosencephaly
Funder
National Health and Medical Research Council
Funding Amount
$624,145.00
Summary
The brain is the most complex organ in the human body and diseases or disorders of the brain can become evident at any stage of life. Generally such problems have profound consequnces for the affected individuals and their families. One of the most common problems of brain development that is evident either at birth or within the first years of life is called holoprosencephaly (HPE). This condition affects the midline of the brain and the face and can lead to delay in mental, motor and language ....The brain is the most complex organ in the human body and diseases or disorders of the brain can become evident at any stage of life. Generally such problems have profound consequnces for the affected individuals and their families. One of the most common problems of brain development that is evident either at birth or within the first years of life is called holoprosencephaly (HPE). This condition affects the midline of the brain and the face and can lead to delay in mental, motor and language development, seizures, and obvious facial abnormalities. In its most severe form only one eye develops in the middle of the face, a condition known as cyclopia and a large majority of the severely affected children will die late in gestation or at birth. This condition can be inherited, but because the genetic lesions that cause this problem affect different people differently, people can carry the causative genetic change(s) without knowing it. We need to identify and study the genetic lesions that contribute to this condition in order to begin to understand how we can stop these mutations affecting the developing foetus. Because it is difficult to study embryonic development in humans we have generated a mouse model of this condition. In the mouse model just one gene (called Zic2) is altered and embryos that have two copies of this alteration develop the most severe form of cyclopia and die in the second half of gestation. This means that the normal role of this gene is to stop us developing HPE. We will use this mouse model to see just when and how the Zic2 gene prevents HPE. In addition, we will look to see what other genes Zic2 interacts with by breeding mice that carry the mutation in Zic2 with mice that carry a mutation in a second gene that can also cause HPE. These experiments are very important because if we understand how Zic2 and other genes protect us from HPE we can begin to design strategies to decrease the risk of a child developing this condition.Read moreRead less
Thalamic And Basal Forebrain Contributions To Auditory Cortical Reorganization Produced By Partial Hearing Loss
Funder
National Health and Medical Research Council
Funding Amount
$364,768.00
Summary
When part of the cochlea is damaged in adult animals, leading to a partial hearing loss, the auditory area of the cerebral cortex reorganizes itself, so that the area deprived of input by the peripheral lesion is not silent, but is occupied by expanded representations of adjacent frequencies. This reorganization has been observed in a number of species, including non-human primates, and it seems likely that it also occurs in humans with cochlear damage and hearing loss of this sort. If it does, ....When part of the cochlea is damaged in adult animals, leading to a partial hearing loss, the auditory area of the cerebral cortex reorganizes itself, so that the area deprived of input by the peripheral lesion is not silent, but is occupied by expanded representations of adjacent frequencies. This reorganization has been observed in a number of species, including non-human primates, and it seems likely that it also occurs in humans with cochlear damage and hearing loss of this sort. If it does, it would have important consequences for the way in which input from a hearing aid or cochlear prosthesis (bionic ear) is processed in the brain. This Project is designed to clarify the nature of the systems in the brain that contribute to this form of cortical plasticity, using an animal model. One aim is to determine whether the plasticity is intrinsic to the cortex or occurs in the pathways over which information is conveyed to the cortex. This will be assessed by determining whether such plasticity is also found in the auditory thalamus, the final subcortical auditory nucleus from which information is sent to the cortex. The second aim is to determine whether the occurrence of plasticity is controlled by modulatory influences from the basal part of the forebrain. Neurons in this area project to many parts of the cortex, and evidence from other sensory systems suggests that these projections exert a permissive function, allowing the cortex to reorganize when input is altered. This aim will be pursued by determining whether cortical reorganization occurs after hearing loss when this basal forebrain system is inactivated. The significance of these studies is that they will elucidate the way in which the brain reorganizes itself when it is confronted with altered input. This information is important for our understanding of normal auditory information processing mechanisms and of the way in which input from prosthetic devices is processed in the hearing-impaired.Read moreRead less
Amelioration Of The Cognitive Deficits In A Model Of Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$542,890.00
Summary
The project investigates a brain molecule called p75, and the part it plays inmemory impairment in Alzheimer's Disease (AD). We predict that p75 is a vital link in the disease processes affecting memory.This research has the potential to lead to an effective treatment for AD, by stimulating work on compounds with the ability to blockthe damaging functions of p75.
Disorders of sexual development (DSDs) are surprisingly common, and often result in infertility, genital abnormalities, gender mis-assignment and long-term psychological trauma. In this Program we will pool our expertise in human molecular genetics, mouse developmental biology and protein chemistry to identify genes important for sex determination and development of the gonads, and discover how they contribute to DSD, in order to improve clinical care to patients with DSD.
Understanding And Preventing Adverse Developmental Effects Of Perinatal Infection/inflammation
Funder
National Health and Medical Research Council
Funding Amount
$621,458.00
Summary
Exposure of babies to infection or inflammation within the womb is common and is associated with preterm delivery and illness in newborns. The biggest problem for these babies is lung disease due to inflammation of the lungs before birth and/or in response to lung injury after birth. We are investigating how inflammation alters lung development, and working on developing a novel cell therapy to prevent life-threatening newborn lung disease.
Molecular Genetics Of Sex Determination And Gonad Development
Funder
National Health and Medical Research Council
Funding Amount
$4,580,898.00
Summary
Intersex disorders - ranging in severity from hypospadias (misplacement of the urethral opening) to complete sex reversal - are surprisingly common, with estimates as high as 4% of all live births. These disorders usually result in infertility, genital abnormalities, gender mis-assignment and long-term psychological trauma. The cause of these problems is most often the failure of the delicate network of gene regulation that is responsible for proper development of testes or ovaries in the embryo ....Intersex disorders - ranging in severity from hypospadias (misplacement of the urethral opening) to complete sex reversal - are surprisingly common, with estimates as high as 4% of all live births. These disorders usually result in infertility, genital abnormalities, gender mis-assignment and long-term psychological trauma. The cause of these problems is most often the failure of the delicate network of gene regulation that is responsible for proper development of testes or ovaries in the embryo. This research program will identify genes important for sex determination and development of the gonads, find out how these genes function and interact, and discover how they contribute to cases of aberrant sexual development in humans. Australia boasts three of the foremost international researchers in sex determination. Their contributions have been fundamental to the advancement of the field, including the identification and characterization of the master testis determining gene and other genes critical for sex determination. They now propose to pool their expertise in human molecular genetics, mouse developmental biology and protein chemistry to bring spectacular advances in our knowledge of human sexual development and its associated disorders. This information will be used to bring improved clinical care to patients withdisorders of sexual development.Read moreRead less