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MECHANISMS OF ABNORMAL EXPRESSION OF THE IGF2 GENE IN DISORDERS AFFECTING FOETAL GROWTH
Funder
National Health and Medical Research Council
Funding Amount
$560,434.00
Summary
The IGF2 gene is crucial for foetal growth. Only the copy inherited from the father is active, a phenomenon named parental imprinting. In some children with foetal overgrowth or growth retardation, the deregulation of imprinting of the IGF2 gene during the first days of foetal development will influence subsequent growth and will also have major implications in post-natal and adult life. We will investigate the mechanisms resulting in abnormal imprinting of the IGF2 early in development.
Characterisation Of Neuregulin-2 Function In The Nervous System.
Funder
National Health and Medical Research Council
Funding Amount
$183,250.00
Summary
The Neuregulins (NRG's) are a family of four structurally related growth factors expressed in the developing and adult brain. NRG-1 is essential for life and has been implicated in the development and maintenance of both neurons and glial cells, as well as being essential for normal heart formation. NRG-2 was identified by us and others as being closely related to NRG-1 and, like NRG-1, it is also expressed predominantly in neuronal populations of the brain. One striking feature of NRG-2 express ....The Neuregulins (NRG's) are a family of four structurally related growth factors expressed in the developing and adult brain. NRG-1 is essential for life and has been implicated in the development and maintenance of both neurons and glial cells, as well as being essential for normal heart formation. NRG-2 was identified by us and others as being closely related to NRG-1 and, like NRG-1, it is also expressed predominantly in neuronal populations of the brain. One striking feature of NRG-2 expression in the adult brain is its localisation to regions associated with neurogenesis (renewal of neurons from stem cell precursors). Outside the nervous system Neuregulin-2 can stimulate the proliferation and differentiation of epithelial cells. However, little is known about the activity of Neuregulin-2 in the brain. This grant proposal aims to study the biological functions of Neuregulin-2 in the developing and adult central nervous system. The experimental design is based on characterisation of mice that do not contain the Neuregulin-2 gene. We will also look specifically at the action of Neuregulin-2 on discrete populations of neuronal cells, grown in tissue culture. We expect that these studies will provide valuable insight into the role of NRG-2 in the brain and that they will be the basis for defining the mechanisms by which NRG-2 activity differs to that of the NRG family members. By studying factors that are involved in the development of the nervous system it is hoped that valuable insights will be made regarding repair and regeneration in the adult brain.Read moreRead less
Understanding Skeletal Development: A Non-proteolytic Mechanism Of Aggrecan Resorption In The Growth Plate
Funder
National Health and Medical Research Council
Funding Amount
$563,044.00
Summary
Bone formation requires resorption of a cartilage template. We challenge the dogma that cartilage resorption is only by PROTEASES, and propose instead that GLYCOSIDASES might also be involved. Aims: Demonstrate that chondrocytes release glycosidases that are important for bone formation. Significance: New information for the design of reconstructive therapies for people with congenital and acquired limb deficiencies or inherited disorders such as arthritis and chondrodysplasias may be gained.
Teeth And Faces Of Australian Twins: A Longitudinal Study
Funder
National Health and Medical Research Council
Funding Amount
$647,226.00
Summary
We are seeking support from the NHMRC to complete a longitudinal study of 250 pairs of twins, both identical and non-identical, whom we have examined at around 4-6 years of age when all the baby teeth were present in the mouth, then again at around 8-10 years of age when both primary and permanent teeth were present. We now plan to examine these twins again at around the age of 11-13 years when all the permanent teeth, except the wisdom teeth, are normally present. Records to be obtained from th ....We are seeking support from the NHMRC to complete a longitudinal study of 250 pairs of twins, both identical and non-identical, whom we have examined at around 4-6 years of age when all the baby teeth were present in the mouth, then again at around 8-10 years of age when both primary and permanent teeth were present. We now plan to examine these twins again at around the age of 11-13 years when all the permanent teeth, except the wisdom teeth, are normally present. Records to be obtained from the twins over the next three years will include dental examinations, dental impressions from which casts can be made, shed primary teeth, and intra- and extra-oral photographs. We will apply modern methods of genetic analysis to determine the importance of genetic and environmental influences on observed variation in several dental and facial features. We will also study the fascinating phenomenon of mirror imaging in twins, where one twin mirrors the other for one or more features. Longitudinal studies of twins, in which a large sample of children is studied over several years, provide a powerful means of determining how genes influence growth and development. As far as we are aware, ours is the only large-scale longitudinal study of dental and facial growth in twins being undertaken in the world at present. Once we have collected all the data and carried out analyses, we will gain a much better understanding of the factors that can influence development of the teeth and face, and be in a much better position to be able to predict those children who are most likely to develop malocclusions in later life.Read moreRead less
Novel Pathways Involving APC And PAR-2 In Cartilage Degradation In Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$448,834.00
Summary
Loss of the cartilage that normally lines the ends of bones is central to joint failure in arthritis and the need for replacement surgery. There are presently no treatments that stop cartilage breakdown in joint disease. This project investigates the role of a new pathway not previously thought to be active in cartilage, in the progressive damage seen in arthritis. Successful completion of these studies may provide a novel new strategy to treat joint disease.
Defining Genetic And Epigenetic Variation During Early Development
Funder
National Health and Medical Research Council
Funding Amount
$996,075.00
Summary
We all began life with a set of genes inherited from our parents. However, it's now known that from the time we were in the womb onwards that genes can be turned off and on by the environment or even completely lost or gained. Even what your mother ate or how she behaved while she was pregnant could have influenced your future health. Because people are so different, we are studying the subtle differences between twins to tease out the factors that may influence our genes and our health.