Functional Significance Of MeCP2 Target Genes In The Pathogenesis Of Rett Syndrome.
Funder
National Health and Medical Research Council
Funding Amount
$476,815.00
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 is a genetic disorder and contributes to a substantial proportion of girls with severe mental retardation. In 1999, a g ....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 is a genetic disorder and contributes to a substantial proportion of girls with severe mental retardation. In 1999, a gene (called MECP2) was identified which appears to be the cause of RTT in at least 80% of affected girls and women. Now that the gene responsible for many cases of RTT has been found, new questions are being asked. Why are the effects of these mutations restricted to the brain? Which other genes might play a role in the symptoms seen in RTT? The focus of this research project is to examine these 2 questions. Using new research techniques, we have identified genes that are themselves secondarily affected by mutations in the MECP2 gene. We wish to study these genes in more detail, with the aim being to gain a greater understanding of how these genes contribute to the onset of impaired brain function in girls and women with RTT. These insights are essential foundations for the development and evaluation of new and more specific therapies for this as yet incurable disorder.Read moreRead less
Pathogenesis Of Rett Syndrome: Molecular Genetics And Animal Models
Funder
National Health and Medical Research Council
Funding Amount
$437,310.00
Summary
Rett syndrome (RS) is a devastating progressive genetic disorder affecting motor and intellectual development, and occurs almost exclusively in females. 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 girl ....Rett syndrome (RS) is a devastating progressive genetic disorder affecting motor and intellectual development, and occurs almost exclusively in females. 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. Mutations in a gene called MECP2 appears to be the cause of RS in up to 80% of affected girls and women. Now that the gene responsible for many cases of RS has been found, there are many new questions. Do all girls with RS have mutations in the MECP2 gene? Will knowing the exact mutation in the MECP2 gene be of help in predicting how severe the disorder will be in individual patients? Why is it that the brain appears to be primarily affected? Which other genes might play a role in the symptoms seen in RS? Could it be possible to develop specific treatments for RS? This research will address a number of important issues. Firstly, our genetic studies of RS subjects will result in early diagnosis, which is often delayed until after a child turns 5 years of age. Secondly, we are developing mouse models of the human disease, which will put us in a much better position in beginning to understand the biological basis of RS. Early diagnosis may enable the initiation of early treatment strategies in the short term, with the long-term goal of developing specific therapies that may potentially cure the disorder. Finally it will enable accurate genetic counselling for both the immediate and extended family members.Read moreRead less
Epigenetic Regulation Of Self Renewal And Lineage Commitment In Haematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$1,104,930.00
Summary
The process by which all our mature blood cells are produced and sustained remains largely unknown. Underpinning the cell fate decisions made through blood cell development is the tightly regulated expression of key genes and proteins that subsequently direct the process of blood cell differentiation. This project will aim study and uncover the molecular mechanisms that coordinate the key gene expression programs that lead to normal blood cell development.
Pathways That Regulate Nuclear Export Of Circular RNA
Funder
National Health and Medical Research Council
Funding Amount
$933,327.00
Summary
An emerging and unusual class of RNA molecules, circular RNAs (circRNAs), is widespread and plays important roles in cancer initiation and progression. However, the pathways responsible for nuclear export of circRNAs are unknown. We propose here to systematically determine how circRNAs are exported from the nucleus and characterise the effect of modulating circRNA export pathways in cancer. This will enable us to determine whether circRNAs can function as a biomarker of patient response.