I am a biochemical geneticist working on the genetics and pathogenesis of mitochondrial energy generation disorders. I have a particular focus on the severe mitochondrial diseases of childhood but am also studying mitochondrial involvement in common disor
STK9, A Second Rett Syndrome Gene: Genetic And Functional Studies
Funder
National Health and Medical Research Council
Funding Amount
$468,750.00
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 may be the most common cause of progressive mental retardation in girls, with an estimated prevalence in Australia of 1 ....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 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. It is a genetic disorder and occurs almost exclusively in females. In 1999, a gene (called MECP2) was identified which appears to be the cause of RTT in most girls and women with RTT. However, for 5 - 10% of RTT subjects, no gene change is found in the MECP2 gene, raising the possibility that other genes may also be responsible for RTT. Our research group has identified one of these genes. Known as STK9, little is known about this gene's function. Of great interest is the fact that our studies suggest that STK9 could also be a caus of intellectual disability in other patients, and with autism. The focus of this research project is to explore how common gene changes in STK9 are in a large number of children with RTT, intellectual disability and seizures, and autism with intellectual disability and seizures. Using cutting edge research technology, we will go on to study how STK9 interacts with MECP2 and other genes, in order to better understand how these genes may be detrimentally affecting brain function in girls and women with Rett syndrome and other neurological disorders. These studies will give us a greater understanding of normal brain development and function.Read moreRead less
Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specifi ....Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specific key genes deregulated in cancer, to correct their expression and stably reprogram the phenotype of the tumour cell in a normal-like state. It outlines the engineering of novel synthetic agents to block specific protein-protein interactions in cancer cells and to induce potent tumour cell death. This work will generate novel and selective therapeutics to treat un-curable forms of tumours.Read moreRead less
Defining The Genomic Basis Of Mitochondrial Complex I Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$639,682.00
Summary
The human genome project led to new technologies that will revolutionise genetic testing. Previously, we could only sequence genes one at a time. Next Generation sequencing allows analysis of hundreds or thousands of genes simultaneously. We will analyse 90 genes in 100 children with severe disorders of mitochondrial energy generation. This will provide proof of principle for the introduction of this technology into routine medical testing and identify new genes causing these diseases.
Skeletome - A Curated Online Knowledge Base Integrating Clinical and Biological Information on Skeletal Dysplasias and Related Conditions. The skeletal dysplasia knowledge base will:
* establish Australia as a world-leader in skeletal dysplasia research;
* provide researchers with an extensible and comprehensive online knowledge-base related to skeletal dysplasias;
* enhance clinicians' understanding of the diagnosis, treatment and management of skeletal dysplasias;
* facilitate collaborativ ....Skeletome - A Curated Online Knowledge Base Integrating Clinical and Biological Information on Skeletal Dysplasias and Related Conditions. The skeletal dysplasia knowledge base will:
* establish Australia as a world-leader in skeletal dysplasia research;
* provide researchers with an extensible and comprehensive online knowledge-base related to skeletal dysplasias;
* enhance clinicians' understanding of the diagnosis, treatment and management of skeletal dysplasias;
* facilitate collaborative discussions by patients, clinicians and researchers around specific cases to improve training, management and diagnosis; and
* enhance Australia's research expertise in Semantic Web and social networking technologies.Read moreRead less
Genomic Signposts, High-resolution Sequencing And Novel Genes In Eye Disease
Funder
National Health and Medical Research Council
Funding Amount
$333,694.00
Summary
Blindness is a very distressing sensory loss. Hereditary eye disorders account for the vision impairment in at least one-third of people who are registered as blind. These disorders cause blindness from a young age and work productivity is significantly impaired. This project will identify novel genetic factors in blinding eye disorders. Identifying these genetic factors will lead to better early detection methods for people and improved treatments to prevent the blindness.
Clinical Efficacy Of Haematopoietic Stem Cell Transplantation In Mucopolysaccharidosis IIIA
Funder
National Health and Medical Research Council
Funding Amount
$508,051.00
Summary
Lysosomal storage disorders (LSD) are inherited diseases that affect about 1 in 7700 Australian children; all share common physical symptoms include heart and breathing difficulties, stiff joints, skeletal deformities, enlarged head, and a characteristic facial appearance. Two-thirds of patients will also develop brain disease. The lysosome is a component of each cell in the human body; its role it is to break down and remove waste from the cell. This involves a series of proteins (enzymes) that ....Lysosomal storage disorders (LSD) are inherited diseases that affect about 1 in 7700 Australian children; all share common physical symptoms include heart and breathing difficulties, stiff joints, skeletal deformities, enlarged head, and a characteristic facial appearance. Two-thirds of patients will also develop brain disease. The lysosome is a component of each cell in the human body; its role it is to break down and remove waste from the cell. This involves a series of proteins (enzymes) that act in sequence. A LSD arises when the lysosome lacks the activity of one protein in this chain. This loss of protein activity means that the waste removal process is impaired. Waste begins to 'store', clogging the cell and interfering with its usual functions. This gives rise to devastating symptoms that worsen over time as storage increases. Brain disease in LSD has profound effects on the child: mental capacity declines, they become hyperactive and aggressive and progressively lose learned skills (e.g. walking, talking) and control of bodily functions. Mucopolysaccharidosis (or MPS) type IIIA is a LSD that affects the brain. Bone marrow transplantation (BMT) is an accepted treatment for many diseases, including cancer. However, unlike cancer and some LSD, BMT does not work in MPS IIIA children. The reasons for this are unknown. This project is important in understanding the basic mechanisms that prevent this form of therapy from working in these children. If we can understand what prevents its effectiveness, we can devise methods to overcome it and potentially offer MPS IIIA (and other LSD that do not respond to BMT) a viable treatment option. We have a colony of mice affected by MPS IIIA; their symptoms are similar to that seen in humans, making them ideal for this study.Read moreRead less
Impact of the male germ line on the mutational load carried by mammalian embryos. This project examines whether a man's age or exposure to lifestyle factors (alcohol, cigarette smoke and mobile phone radiation) can have a major effect on the health of his children. The project is particularly relevant to the safety of assisted conception procedures used to treat the 1 in 20 Australian men suffering from infertility.