The Role Of GRHL-3, A Mammalian Homologue Of Drosophila Grainyhead, In Neural Tube Development
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first ....Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first few hours of life. These abnormalities occur frequently (1-1000 live births) and are a direct result of failure of the neural tube to close during embryogenesis. NTDs are influenced by both environmental and genetic factors. The best characterised environmental factor is the dietary supplement folate, which when administered before conception results in a reduction in the incidence of spina bifida. The genetic complexity is evidenced by the array of mouse genetic mutations that give rise to NTDs. One of these mouse mutations, known as Curly tail (ct), has served as the major animal model of human NTDs. This is because the ct mice are resistant to folate administration (like most of the cases of spina bifida currently seen in patients) and because the mice seem to have normal development in virtually all other organ systems. Ironically, the genetic mutation that causes the curly tail phenotype has remained undiscovered for over 50 years. We have now identified the gene mutated in the curly tail mice. This gene is highly conserved in humans suggesting that it will play a similar role in neural tube development in man. The gene, known as GRHL-3, is a descendant of a fly gene critical for development of the nervous system in that organism. The studies we propose here will examine the developmental pathways involved in normal neural tube closure in mice and humans and will impact on our understanding of these devastating congenital malformations.Read moreRead less
Improving Oocyte Mitochondrial DNA Copy Number To Enhance Female Reproductive Capacity.
Funder
National Health and Medical Research Council
Funding Amount
$670,867.00
Summary
Eggs with too few copies of mitochondrial DNA either fail to fertilise or arrest during early development. By supplementing eggs with mitochondrial DNA, we have been able to enhance embryo quality and gene expression profiles. By breeding the offspring derived from eggs given mitochondrial supplementation, we will determine if they and their progeny meet normal developmental milestones, regulate the transmission of mitochondrial DNA appropriately, and are healthy and fertile.
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.
Investigating A Theoretical Model Of Cognitive Control In Children With Attention Deficit Hyperactivity Disorder (ADHD): Informing Our Approach To Cognitive Training.
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
ADHD is the most common childhood developmental disorder, characterised by inattentive and/or hyperactive behaviours. Cognitive control has been highlighted as a potential mediator of ADHD symptoms. This program will i) delineate the relationship between cognitive control and ADHD symptoms, ii) develop a cognitive training intervention to target the underlying mechanisms identified as mediators of ADHD symptoms and iii) evaluate the program in a gold-standard clinical trial.
Regulation Of Neural Progenitor Cell Self-renewal By The RNA-binding Protein ZFP36L1 During Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$345,401.00
Summary
The timely differentiation of neural stem cells is critical during development, and the unrestrained proliferation of neural stem cells in the adult can lead to deadly brain cancers such as glioma. At present our understanding of the key molecules that regulate neural stem cell behaviour during these processes remains limited. In this proposal we will investigate the molecular determinants underpinning neural stem cell biology, both within the developing brain, and within glioma.
Early career teacher induction: Supporting precarious teachers. This project aims to investigate the ways in which Australian induction policies support precariously employed early career teachers to effectively manage student classroom behaviour. This project expects to generate new knowledge of workforce development and induction experiences of early career teachers employed on casual and short-term contracts. Expected outcomes of this project include alternative policy and practice recommenda ....Early career teacher induction: Supporting precarious teachers. This project aims to investigate the ways in which Australian induction policies support precariously employed early career teachers to effectively manage student classroom behaviour. This project expects to generate new knowledge of workforce development and induction experiences of early career teachers employed on casual and short-term contracts. Expected outcomes of this project include alternative policy and practice recommendations to support the transition of insecure replacement teachers within the profession. The benefits of this research include, improving teachers’ classroom management practices; the retention of new teachers; improving teacher workforce development; and building a healthier education system. Read moreRead less
Investigating the effectiveness of teacher education for early career teachers in diverse settings: a longitudinal study. This project investigates the effectiveness of teacher education programs in Victoria and Queensland in preparing teachers for the variety of school settings in which they begin their careers. The findings will inform state and national policy, as well as the work of professional regulation authorities and teacher education providers.
An Inside-out Approach To Muscosal Vaccination: MAdCAM Targeting
Funder
National Health and Medical Research Council
Funding Amount
$174,250.00
Summary
The mucosal surfaces are the entry site for many pathogens (eg. cholera, rotaviruses, helicobacter, SARS and sexually transmitted diseases including HIV infections). The ideal vaccine would elicit both systemic and mucosal immune response, enhancing immunity at this first line of defence. The oral route has formidable barriers to antigen uptake such as digestive enzymes, commensal microbes, mucous layers and gastric acid. Our strategy targets the vascular addressin found in immune tissues of the ....The mucosal surfaces are the entry site for many pathogens (eg. cholera, rotaviruses, helicobacter, SARS and sexually transmitted diseases including HIV infections). The ideal vaccine would elicit both systemic and mucosal immune response, enhancing immunity at this first line of defence. The oral route has formidable barriers to antigen uptake such as digestive enzymes, commensal microbes, mucous layers and gastric acid. Our strategy targets the vascular addressin found in immune tissues of the gut (called MAdCAM) so that the vaccine is linked to an antibody against MAdCAM. Thus for the first time we believe that a parenteral vaccine ie. injected im or iv (bypassing the oral barriers) can induce mucosal immunity.Read moreRead less
Intercultural understanding in primary and secondary schools. What facilitates or impedes intercultural understanding in children, adolescents and schools? How can this be addressed? How can we know what makes a difference? This project answers these questions at the individual, school and national level using a novel cultural systems approach and methodological and technological innovations.
Naming the world: early years literacy and sustainability learning. The project seeks to produce knowledge about new forms of literacy emerging in sustainability education. For children born in the 21st century, the enmeshing of natural and human forces in the survival of the planet requires conceptual and practical innovation. Early childhood education can be a fundamental driver in this process. This project aims to integrate literacy and sustainability to produce powerful new learning for you ....Naming the world: early years literacy and sustainability learning. The project seeks to produce knowledge about new forms of literacy emerging in sustainability education. For children born in the 21st century, the enmeshing of natural and human forces in the survival of the planet requires conceptual and practical innovation. Early childhood education can be a fundamental driver in this process. This project aims to integrate literacy and sustainability to produce powerful new learning for young children. It plans to theorise new forms of literacy emerging in sustainability education, articulate innovative pedagogies, and inform national and international policy and practice to address 21st century learning imperatives.Read moreRead less