Transcriptional Regulation Of Gene Expression: Dietary Sialic Acid Interaction In Brain Cognitive Development
Funder
National Health and Medical Research Council
Funding Amount
$46,646.00
Summary
In 2004, 8.2% of Australian live births were preterm with poor long-term cognitive outcomes. Sialic acid (SA), a key component of both human milk oligosaccharides and neural tissues, plays a role in neuronal development. This study will examine the mechanisms of how dietary SA or active learning interacts with genes during brain development. It will benefit the neonatal care of all children, particularly those born premature and ultimately, the quality of life of many Australians.
THE ROLE OF SIALIC ACID IN INFANT NUTRITION AND BRAIN DEVELOPMENT
Funder
National Health and Medical Research Council
Funding Amount
$402,750.00
Summary
Sub-optimal nutrition during critical periods of brain growth has persistent effects on the human brain. Premature infants are especially vulnerable because brain growth reaches its peak at 26 weeks gestation and remains high throughout the first year of life. Those fed human milk in the first month after birth have been shown to have a significant intellectual advantage compared with infants fed standard infant formulas. While the n-3 fatty acids such as DHA are thought to be important, other c ....Sub-optimal nutrition during critical periods of brain growth has persistent effects on the human brain. Premature infants are especially vulnerable because brain growth reaches its peak at 26 weeks gestation and remains high throughout the first year of life. Those fed human milk in the first month after birth have been shown to have a significant intellectual advantage compared with infants fed standard infant formulas. While the n-3 fatty acids such as DHA are thought to be important, other components of human milk may be of greater significance for brain growth. Our interest is in a sugar compound called sialic acid. It occurs in remarkably large amounts in human milk (up to 1g-L) but is present in only small quantities in infant formulas. Sialic acid is an important structural and functional component of brain cells. It is directly involved in nerve cell transmission, memory formation and cell-to-cell communication. During peak brain growth, young infants, especially pre-term ones, are unlikely to be able to synthesise sufficient sialic acid to meet their needs. At these times, they rely on human milk and infant formulas to supply the necessary building blocks. If their diet is a poor source of sialic acid, however, there may be lasting consequences for intellectual development. This research project addresses several questions. 1. Does oral sialic acid supplementation over the first few weeks of life increase both brain sialic acid levels as well as learning behaviour? 2. Is there any dose-response relationship - is more better? 3. Does supplementation influence the expression of genes encoding key enzymes in the brain? 4. Does dietary supplementation affect the activity of the liver enzyme involved in synthesis of sialic acid? If our findings can be extrapolated to human infants, they will have implications for the etiology of all types of cognitive and behavioural defects in children, including learning difficulties and attention deficit disorder.Read moreRead less
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
Modern Chemical Exposures In Utero And In Infancy, And Their Impact Upon Early Neurodevelopmental Outcomes In The Barwon Infant Study, An Unselected Birth Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$138,353.00
Summary
I am a paediatric doctor interested in the effects of modern industrial chemicals on children’s development. Even in the womb babies are exposed to industrial chemicals and we know some, like lead, are harmful to developing brains. I am interested in other chemicals that are now suspected to affect development, including the polybrominated diphenyl esters (PBDEs), and I intend to investigate this as part of the Barwon Infant Study, which follows 1250 children from before birth to 3 years.
Developing An In Vitro Model Of A Human Blastocyst
Funder
National Health and Medical Research Council
Funding Amount
$890,062.00
Summary
Using novel cellular and molecular technologies we propose to develop an artificial model of an early human blastocyst. This will allow us to study the first initial steps in human development without the use of real embryos. Such a model will not only help us decipher the first steps in human development, but we anticipate it will be essential to study how gene mutations and the environment affect this initial step in human development.
Characterisation Of Eurl, A Novel Gene Implicated In The Etiology Of Abnormal Brain Development And Intellectual Disability
Funder
National Health and Medical Research Council
Funding Amount
$597,541.00
Summary
Intellectual disability affects around one per cent of Australians, and can arise from genetic abnormalities during fetal life, such as through abnormal regulation of gene expression. We have identified a novel gene, known as eurl, which controls brain assembly as well as the ability of neurons to form functional connections within the brain. We will investigate how this novel gene controls brain development, and characterise eurl as a potential therapeutic target for learning and memory.