Molecular Basis Of Mitochondrial Complex I Deficiency, The Most Common Energy Generation Disorder
Funder
National Health and Medical Research Council
Funding Amount
$515,750.00
Summary
Oxygen is needed by every cell in the body to burn fuels (ie sugar, fat and protein) in small power plants inside each cell called mitochondria. In Australia, about 50 children born each year have inherited disorders of mitochondrial energy generation. The most severe disorders cause infant death, while others cause a range of degenerative diseases later in life, particularly affecting brain, muscle and heart. In most cases we do not have any effective treatments. A major problem in understandin ....Oxygen is needed by every cell in the body to burn fuels (ie sugar, fat and protein) in small power plants inside each cell called mitochondria. In Australia, about 50 children born each year have inherited disorders of mitochondrial energy generation. The most severe disorders cause infant death, while others cause a range of degenerative diseases later in life, particularly affecting brain, muscle and heart. In most cases we do not have any effective treatments. A major problem in understanding mitochondrial energy generation disorders is that the genetic causes are incredibly diverse. So far more than 20 genes have been shown to cause mitochondrial disorders, and it is likely that over one hundred more genes remain to be discovered. In addition to the regular genes that cause these and other genetic disorders, mitochondria are unique in carrying 37 extra genes located in a different part of the cell away from the rest of the human genome, and inherited only from the mother. This grant focuses on the most common energy generation disorder, known as Complex I deficiency. Complex I requires 43 separate components to be assembled together in order to work properly, but mutations in the 43 genes encoding these components are not present in most patients. We believe that the most common problems will be in genes involved in assembling the 43 components rather than in the components themselves. We will use a number of methods to pinpoint where in the genome the causative genes are located and then home in on the exact changes in the genes that cause disease. Identifying these genes will allow us to improve future diagnosis and prevention of mitochondrial disease. Understanding the basic biology may also allow us to develop new methods of treatment. Recent studies suggest that milder mitochondrial problems also contribute to a range of more common diseases such as diabetes and Parkinson disease, so any new treatments could potentially have wide application.Read moreRead less
First Generation Mouse Models Of MtDNA Disease: Testing Genotype/phenotype Predictions
Funder
National Health and Medical Research Council
Funding Amount
$256,527.00
Summary
Mitochondrial diseases comprise a diverse group of inherited diseases affecting infants, children and adults. These disorders result from defective energy production by the mitochondria, tiny structures in all cells which have their own unique DNA. This mitochondrial DNA is inherited only from our mothers. To make energy for cells to function normally, special enzymes are produced in the mitochondria from mitochondrial and nuclear genes. In their most severe form mitochondrial disease results in ....Mitochondrial diseases comprise a diverse group of inherited diseases affecting infants, children and adults. These disorders result from defective energy production by the mitochondria, tiny structures in all cells which have their own unique DNA. This mitochondrial DNA is inherited only from our mothers. To make energy for cells to function normally, special enzymes are produced in the mitochondria from mitochondrial and nuclear genes. In their most severe form mitochondrial disease results in infants with muti-system failure. Adult forms are less severe, with symptoms including epilepsy, cardiomyopathy, late-onset blindness or deafness, and commonly diabetes. We do not understand why different mitochondrial mutations result in such diverse symptoms, and no therapies have been consistently successful. Unusual features of mitochondrial DNA has meant that it has remained beyond the reach of techniques which are commonly used now to produce mice with altered genes. These so-called 'mouse models' are powerful tools to better understand human diseases and importantly, to enable experimental therapies to be tested and improved. This grant proposes a novel method of producing such mouse models, for the first time allowing mice with different levels of defective mitochondrial function to be produced to model the human diseases. In the proposed work, mitochondria from different mouse species will be introduced into laboratory mice. This unusual approach is based on previous work by the investigators who have shown that this produces defective mitochondria in cultured mouse cells. These mice will be allowed to age and the function of mitochondria from different organs tested as the animals age. Secondly, a range of mitochondrial DNA mutations will be produced in cultured cells and mutants selected to make other mice which should accurately model the diverse human diseases.Read moreRead less
QTL Linkage Analysis For Complex Human Traits In Twin Families
Funder
National Health and Medical Research Council
Funding Amount
$1,000,000.00
Summary
This project will focus on finding genes for common human diseases. Now that the human genome has been sequenced, the race is on to find out what the estimated 38,000 human genes do and which ones are associated with which diseases. Scattered throughout the genome are small variations in DNA sequence, some of which increase the odds of disease while others are protective.
Epigenetic Hyperglycemic Cell Memory Causes Vascular Complications In Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$332,140.00
Summary
This project seeks to identify how epigenetic change in response to hyperglycemia can cause vascular complications of diabetes, and how this contributes to “hyperglycemic memory”; a phenomena where cells may undergo gene modifications which increase risk to further complications later in a patients life. These studies are the first of their kind and will characterize the types of epigenetic change that can cause human disease.
Genome-wide Association Studies Of Biomedical Traits And Endophenotypes For Complex Disease
Funder
National Health and Medical Research Council
Funding Amount
$295,804.00
Summary
The burden of common complex diseases, such as cardiovascular disease is substantial to the health care system. These diseases are caused by genes and environments as well as their interactions. The proposed project will identify genes affecting the susceptibility of individuals to complex diseases. Discovery of such genes will be important for their diagnosis, prevention and treatment and may serve as an important resource for future personalized medicine.
Mechanisms of zinc transport and homeostasis in plants. Zinc deficiency is a widespread factor limiting crop production and affects many soils of southern Australia and around the world. Genetic techniques can be used to identify zinc-efficient crop breeds able to grow well under zinc deficient conditions and able to efficiently deliver zinc to cereal grains to alleviate nutritional zinc-deficiency in humans. This project will identify new genes important in zinc transport and homeostasis in pla ....Mechanisms of zinc transport and homeostasis in plants. Zinc deficiency is a widespread factor limiting crop production and affects many soils of southern Australia and around the world. Genetic techniques can be used to identify zinc-efficient crop breeds able to grow well under zinc deficient conditions and able to efficiently deliver zinc to cereal grains to alleviate nutritional zinc-deficiency in humans. This project will identify new genes important in zinc transport and homeostasis in plants and will ultimately allow their role in zinc efficient crops to be assessed. This will contribute to more rapid and directed strategies in breeding zinc efficient crops.Read moreRead less
Discovering genes which modify human physical performance: a means of developing healthier life styles & novel athletic training programs. The aim of this multicentred study (University of Sydney, Australian National University, Australian Institute of Sport) is to find genes in the cardiac and musculoskeletal systems that are involved in modifying human physical performance. From this knowledge, it is proposed to develop novel physical training programs in our national sporting institutions ba ....Discovering genes which modify human physical performance: a means of developing healthier life styles & novel athletic training programs. The aim of this multicentred study (University of Sydney, Australian National University, Australian Institute of Sport) is to find genes in the cardiac and musculoskeletal systems that are involved in modifying human physical performance. From this knowledge, it is proposed to develop novel physical training programs in our national sporting institutions based on an individual's genetic information. In the broader community, knowledge of genes which contribute to the normal and healthy functioning of the cardiac and musculoskeletal systems will be invaluable in understanding and preventing breakdowns in these body systems.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668440
Funder
Australian Research Council
Funding Amount
$850,000.00
Summary
Advanced technology for transcriptomics, genomics and gene mapping. Acquistion of the equipment requested in this application will maintain the expertise developed by researchers within New South Wales and attract and retain exceptional individuals who can contribute to our understanding of how genes interact with one another. The benefit of such an enhances facility will be the delivery of a better functional understanding of health and disease which will provide both community and national be ....Advanced technology for transcriptomics, genomics and gene mapping. Acquistion of the equipment requested in this application will maintain the expertise developed by researchers within New South Wales and attract and retain exceptional individuals who can contribute to our understanding of how genes interact with one another. The benefit of such an enhances facility will be the delivery of a better functional understanding of health and disease which will provide both community and national benefits. The primary purpose of this LIEF application is to standardize approaches to the study of genome function across the nodes of the Ramaciotti facility and to expand the capacities of the facility to cope with the increased demand in this technology. Read moreRead less
Special Research Initiatives - Grant ID: SR0354500
Funder
Australian Research Council
Funding Amount
$10,000.00
Summary
ARC Research Network in Microarray Technology. The primary aim of this proposal is to transform the premier genomic technology into a standard research tool; microarrays are now a priority for anyone studying the genetics underlying key biological processes. A principal challenge for the Australian research community is to capture all aspects of microarray technology and make them readily available. We will address these needs by developing a network to:
-establish regular research meetings,
- ....ARC Research Network in Microarray Technology. The primary aim of this proposal is to transform the premier genomic technology into a standard research tool; microarrays are now a priority for anyone studying the genetics underlying key biological processes. A principal challenge for the Australian research community is to capture all aspects of microarray technology and make them readily available. We will address these needs by developing a network to:
-establish regular research meetings,
-facilitate training in array methodologies and bioinformatics,
-co-ordinate innovation of technologies,-provide centralised data warehousing,
-provide access to automated high-level gene annotation,
-provide data mining tools,
-set standards for data management and exchangeRead moreRead less