Epilepsy is a very common and serious brain disorder. Epilepsy often includes other disabilities, reduction in quality of life and is associated with increased risk of early death. 30% of people with epilepsy are unable to gain control of their seizures with currently available medications. The genetic causes of the large majority of epilepsy cases have not yet been found. This project aims to identify new genetic causes of epilepsy and its related disorders.
In Vivo Analysis Of The Molecular And Neural Mechanism That Underly An Association Of MiRNAs With Mental Disorders
Funder
National Health and Medical Research Council
Funding Amount
$593,778.00
Summary
Genetic studies on autism, schizophrenia, bipolar disorder and major depression suggest that these disorders affect the formation and maintenance of connections between neurons. A group of brain-specific microRNAs, which are regulatory molecules, are predicted to regulate connectivity. Levels of these molecules are found to be abnormal in brains of patients with schizophrenia. This proposal aims to elucidate the function of these microRNAs in the number of neuronal connections, and early motor b ....Genetic studies on autism, schizophrenia, bipolar disorder and major depression suggest that these disorders affect the formation and maintenance of connections between neurons. A group of brain-specific microRNAs, which are regulatory molecules, are predicted to regulate connectivity. Levels of these molecules are found to be abnormal in brains of patients with schizophrenia. This proposal aims to elucidate the function of these microRNAs in the number of neuronal connections, and early motor behavior in transgenic zebrafish.Read moreRead less
I aim to decipher the role of heritable, genetic DNA variation in human neurological disease. I will use next generation genomics technologies together with sophisticated cellular models to address the important questions of the biology of epilepsy and intellectual disability in particular. I aim to develop a treatment for a specific type of epilepsy, which affects only girls from the age of 6 months. My ultimate goal is to improve the life of the patients and their relatives.
The Role Of UPF3B And Nonsense Mediated MRNA Decay Surveillance In The Pathology Of Intellectual Disability.
Funder
National Health and Medical Research Council
Funding Amount
$789,954.00
Summary
Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundam ....Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundamental importance.Read moreRead less
Identification Of Genes For X-linked Mental Retardation.
Funder
National Health and Medical Research Council
Funding Amount
$675,228.00
Summary
We propose to identify novel heritable causes of intellectual disability using 22 large and well-characterised families from Australia. In these families we have refined the location of the genetic defect to the chromosome X and excluded the contribution of all so far known genes. We will achieve this using the technology of massive parallel sequencing. At the completion of the project we will have identified novel causes of intellectual disability and devised tests to identify them.
Cell Type Specification In Developing CNS: Functional Analysis Of Sox14
Funder
National Health and Medical Research Council
Funding Amount
$468,055.00
Summary
The central nervous system (CNS) is the most complex organ in the body. The vast majority of nerve cells in the CNS are classified as 'interneurons'. These cells relay sensory information and motor commands within the CNS. Abnormal functioning of interneurons is likely to be the underlying cause of some, if not many, human nervous system diseases. However, very little is known of the precise anatomy and function of interneurons, which genes control their development, and how these functions are ....The central nervous system (CNS) is the most complex organ in the body. The vast majority of nerve cells in the CNS are classified as 'interneurons'. These cells relay sensory information and motor commands within the CNS. Abnormal functioning of interneurons is likely to be the underlying cause of some, if not many, human nervous system diseases. However, very little is known of the precise anatomy and function of interneurons, which genes control their development, and how these functions are maintained in the adult. This has been largely due to a lack of efficient and reliable methods to identify and study interneurons. We have previously discovered that a gene termed Sox14 is active in distinct interneuron groups in the embryonic brain and spinal cord. Sox14 is a member of the Sox gene family, many of which act as genetic switches to control cell and tissue development. We found that Sox14 has been extremely well conserved throughout evolution and is active in similar interneuron groups in a number of animal species. These studies led us to hypothesise that Sox14 controls a critical molecular step in the generation of certain interneurons that may be involved in reflexes, locomotion or motor coordination. In this project, we will investigate both the role of Sox14 in interneuron development and the functions of interneurons in which this gene is active. We will do so by combining modern molecular and genetic techniques with physiological approaches. This project will reveal critical molecular steps in CNS development and determine the functions of a specific group of interneurons. To this end, we will generate mouse strains in which a specific group of interneurons are genetically marked and can be manipulated during development. We envisage that these mice with 'modified brain circuits' will become unique resources for future investigations of selected interneuron types and their functions.Read moreRead less
Genetic And Phenotype Studies Of Partial Epilepsy In Gypsies
Funder
National Health and Medical Research Council
Funding Amount
$646,136.00
Summary
Epilepsy is one of the most common serious neurological disorders, which affects more than 50 million people worldwide. Genetic research, with a major contribution from Australian researchers, has led to the discovery of many rare forms of the disease caused by mutations in single genes of large effect. However, the vast majority of cases worldwide belong to the so-called genetically complex forms, involving multiple interacting genes and environmental factors. The genetically complex epilepsies ....Epilepsy is one of the most common serious neurological disorders, which affects more than 50 million people worldwide. Genetic research, with a major contribution from Australian researchers, has led to the discovery of many rare forms of the disease caused by mutations in single genes of large effect. However, the vast majority of cases worldwide belong to the so-called genetically complex forms, involving multiple interacting genes and environmental factors. The genetically complex epilepsies have proved particularly difficult to understand and the numerous genetic studies conducted so far have failed to produce important and replicable results. It is becoming increasingly clear that enormous genetic heterogeneity, with many rare mutations occurring in different affected subjects, will be a major obstacle to understanding the molecular basis of complex epilepsies. In this context, genetically isolated populations, which stem from a small number of ancestors, can be particularly helpful and revealing, since their limited genetic diversity means that the number of genes involved in causing complex epilepsies may be smaller and shared between individuals and families. In this study, we will analyze affected families, as well as non-familial cases of epilepsy, from a genetically isolated population - the European Roma-Gypsies. We will determine the number of potential susceptibility genes involved in familial forms, the overlap and differences between families, as well as the contribution of the genes identified in families to the development of sporadic epilepsy.Read moreRead less
Neuromuscular Disorders: Gene Discovery And Disease Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$880,569.00
Summary
Inherited muscle disorders lead to lifelong disability and early death. Less that 50% of patients get an accurate diagnosis and there are currently no effective therapies. In this project, two leading Australian laboratories will use state-of-the-art methods to identify novel disease genes and how they cause muscle weakness. This research will have immediate outcomes to diagnosis, management and prevention and for the development of new therapeutic agents.