Genetic And Bioinformatic Analysis Of Complex Human Diseases
Funder
National Health and Medical Research Council
Funding Amount
$8,752,567.00
Summary
Some human diseases are common in families; examples include prostate cancer, blood cancers, epilepsy and diabetes. Therefore, close relatives of individuals with a disease have an increased risk of being affected by this disease, implying a genetic basis. Finding the cause of these diseases is difficult, we will be developing novel approaches to the identification of genes responsible for these diseases. This is the first step towards the development of treatments for affected individuals.
The Genetic Control Of Platelet Production And Function
Funder
National Health and Medical Research Council
Funding Amount
$558,920.00
Summary
Platelets are the tiny cells that circulate in the body and make blood clot. The human body has more than a trillion of them at any one time, and they are replaced every week by the blood producing cells that reside in the bone marrow. Keeping the normal number of platelets steady is incredibly important any significant drop can result in a life-threatening hemorrhage. The clinical name given to a low platelet count is thrombocytopenia, and it is a very common problem. It can be caused by geneti ....Platelets are the tiny cells that circulate in the body and make blood clot. The human body has more than a trillion of them at any one time, and they are replaced every week by the blood producing cells that reside in the bone marrow. Keeping the normal number of platelets steady is incredibly important any significant drop can result in a life-threatening hemorrhage. The clinical name given to a low platelet count is thrombocytopenia, and it is a very common problem. It can be caused by genetic mutations, viral infections, or by cancer treatments like chemotherapy. The only way to raise platelet numbers in a person with thrombocytopenia is a blood transfusion, which carries with it risks and potential side effects. While we understand quite a lot about how the body produces platelets, we don t know anywhere enough to be able to develop new treatments. Our work is focused on the identification of the genes that control the process, beginning with mouse models of thrombocytopenia, genome mapping, gene isolation, and finally, making the links between the newly identified genes and patients with thrombocytopenia. It will give us a much better understanding of how platelets are produced, how things go wrong in human disease, and how new therapies might be developed to treat them.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
Generation Of Mouse Models To Study The Roles Of Different Bcl-2 Family Members In The Regulation Of Apaptosis
Funder
National Health and Medical Research Council
Funding Amount
$420,872.00
Summary
Programmed cell death, or apoptosis, is required for the removal of infected, damaged or unwanted cells and its disrupted regulation is implicated in cancer, autoimmunity and degenerative disorders. The Bcl-2 family of proteins are key regulators of apoptosis. We propose to generate several mouse models to better understand the relationships between the different members of the Bcl-2 family in an effort to control this pathway for therapeutic purposes.
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