Mapping Of Genetic Traits In Experimental Models Using Databases
Funder
National Health and Medical Research Council
Funding Amount
$237,750.00
Summary
The project aims to detect genes that influence human traits. These traits could be a disease such as diabetes or they may be much less sinister, representing hearing range as an example. Many of these traits are difficult to detect because they are governed by many genes which may also interact with the environment to influence the trait. In order to detect genes in these traits we would like to simplify the complex interactions by eliminating the environment as a potential cause or concentrati ....The project aims to detect genes that influence human traits. These traits could be a disease such as diabetes or they may be much less sinister, representing hearing range as an example. Many of these traits are difficult to detect because they are governed by many genes which may also interact with the environment to influence the trait. In order to detect genes in these traits we would like to simplify the complex interactions by eliminating the environment as a potential cause or concentrating on a particular population where the incidence appears to be much greater. In human populations we have no control over the environmental exposures and we cannot restrict their movements. For this reason many genetic studies have been conducted in mice. Many strains of mice have been generated. Their environment can be strictly controlled, enabling a much better identification of disease genes. Since mice and humans share much of their genome they also share many of their genes and are often afflicted by the same diseases. Thus if we identify genes in mice we have a very good chance of identifying the equivalent human genes. The completion of sequencing for the human genome is being closely followed by the completion of the mouse genome, precisely because mice have been used for over 100 years for genetic studies. The data generated from these sequencing efforts and prior genetic studies is now accumulating in vast databases. These databases of DNA information can be used to map genes for traits. The idea is to determine the trait measurement for many mice in different strains and compare these trait levels to the DNA state (genotype) of markers in the genome of the strains. If these are associated it indicates that the marker is situated close to a gene influencing the trait. This narrows the search considerably. Without this strategy we would have the daunting task of identifiying trait genes from many thousands of potential candidates.Read moreRead less
I am a medical retinal specialist who is involved in a spectrum of basic and clinical research into the cause, risk factors, prevention and treatment of age related macular degeneration, the most common cause of vision loss in Australia.
Isolation And Function Of Human Oogenesis Genes Regulating Meiosis, Recruitment, Growth And Maturation Of The Oocyte.
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Reproductive medicine has progressed very rapidly with the development of in vitro fertilization (IVF) and has delivered the opportunity for a broad group of infertile couples to form their own families. As a consequence, treatment of infertility by major surgery and artificial insemination with donor sperm have declined and there is an increasing interest in the use of IVF to diagnose severe genetic disease in embryos of families at risk. However, little is known about the underlying processes ....Reproductive medicine has progressed very rapidly with the development of in vitro fertilization (IVF) and has delivered the opportunity for a broad group of infertile couples to form their own families. As a consequence, treatment of infertility by major surgery and artificial insemination with donor sperm have declined and there is an increasing interest in the use of IVF to diagnose severe genetic disease in embryos of families at risk. However, little is known about the underlying processes that form the follicles containing the developing germ cells and the matured oocytes needed for IVF. The cohort of oocytes that can be harvested from any patient depends on unknown recruitment processes initiating development of a subset of the quiescent germ cells and happens in an unregulated and spontaneous manner. The present project will identify the known and unknown genes involved in recruitment of oocytes from the basal primordial population. These genes will become candidates for aiding infertile women, improving their response to fertility drugs, the development of novel contraceptive methods and potentially increasing the reproductive life span of women. Knowledge of the genes expressed in oocytes matured in vivo and in vitro will have an important bearing on the long-term opportunity to use fertility drugs in vitro instead of administration to patients for IVF. This would dramatically reduce the cost of IVF and the side-effects of hyperstimulation of ovaries of patients and the associated sequelae. The research project is a discovery program leading to the identification of the genes that govern oogenesis in the human. It is only recently that techniques have been developed to sufficient sensitivity to detect the small quantities of RNA proceeded by active genes in the individual germ cells and oocytes.Read moreRead less
In melanoma we hypothesise there is a series of as yet unidentified gene fusions which provide oncogenic stimulatory signals that promote tumour growth and that these novel fusion products are excellent targets for the design of new therapies to treat melanoma. The aims of this study are to identify oncogenic fusions in melanoma, to assess which of these are recurrent, and to demonstrate that the resulting fusion proteins provide a selective growth and-or survival advantage to the tumour cell.
Identification And Characterisation Of Nessy; A Novel Gene Important For T Cell Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$250,500.00
Summary
This project aims to identify, and understand the function of, a new gene involved in the immune system. The Nessy mouse strain was developed in Prof. Goodnow s Medical Genome Centre at the Australian National University. It has a mutation in an unknown gene which causes a defect in T lymphocytes- white blood cells which are important for fighting infection. This project has three major aims: 1) to identify the gene. 2) to understand the defects in T lymphocytes caused by the gene. 3) to identif ....This project aims to identify, and understand the function of, a new gene involved in the immune system. The Nessy mouse strain was developed in Prof. Goodnow s Medical Genome Centre at the Australian National University. It has a mutation in an unknown gene which causes a defect in T lymphocytes- white blood cells which are important for fighting infection. This project has three major aims: 1) to identify the gene. 2) to understand the defects in T lymphocytes caused by the gene. 3) to identify which other genes interact with the mutant gene. Thus will allow us to understand how the mutant gene causes the T lymphocyte defects. This project will improve our understanding of the development and functioning of T lymphocytes, which play a central role in the immune system. Since the genomes of mice and humans are very similar, it is likely that we will be able to identify a human counterpart to the Nessy gene.Read moreRead less
Body Segment Identity Specification By The Transcription Regulator, Moz
Funder
National Health and Medical Research Council
Funding Amount
$366,301.00
Summary
One in 28 newborns have birth defects. Cleft palate and aortic arch defects are among the most common, always requiring surgery and often causing lethality. We propose to study a protein, Moz, which is essential for palate and aortic arch development. Moz (Monocytic leukaemia zinc finger protein) was first identified in human chromosomal abnormalities causing particularly aggressive forms of childhood and adult leukaemia. We have shown previously that Moz is essential for the formation of blood ....One in 28 newborns have birth defects. Cleft palate and aortic arch defects are among the most common, always requiring surgery and often causing lethality. We propose to study a protein, Moz, which is essential for palate and aortic arch development. Moz (Monocytic leukaemia zinc finger protein) was first identified in human chromosomal abnormalities causing particularly aggressive forms of childhood and adult leukaemia. We have shown previously that Moz is essential for the formation of blood stem cells. Moz can regulate the activity of genes, but which genes it regulates in vivo is unknown. In the absence of Moz, mice are born with a cleft palate, lack the thymus, where immune cells are instructed, and fail to form the lung blood circulation, so that they are unable to supply their blood with oxygen after birth. Moz deficiency also causes defects of the vertebrate column, such that individual vertebrae acquire the appearance of their neighbours. These symptoms are typical for a general defect in positional information of individual body segments with respect to their location along the body axis. We will investigate the molecular mechanisms that require Moz in patterning of the body axis. This project will characterize a genetic mechanism that is crucial for normal development of the palate, the aorta and the vertebrate column.Read moreRead less
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.