The presenilin proteins are key components in the development of Alzheimer's disease. Mutations in these proteins can cause early Alzheimer's disease. We will continue our study of the biochemistry and cell biology of these proteins using tools and experimental models that we have already developed. This will provide important information on the mechanism of the disease process and give new leads in the treatment of the disease. The new technologies of genetic screening for presenilin mutations ....The presenilin proteins are key components in the development of Alzheimer's disease. Mutations in these proteins can cause early Alzheimer's disease. We will continue our study of the biochemistry and cell biology of these proteins using tools and experimental models that we have already developed. This will provide important information on the mechanism of the disease process and give new leads in the treatment of the disease. The new technologies of genetic screening for presenilin mutations will be developed and utilized as a National referral base.Read moreRead less
Investigation Into The Roles Of A Novel Vertebrate Gene, S52, In CNS Development And Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$272,389.00
Summary
Developmentally regulated genes when mutated or deleted can cause a variety of diseases including neurological diseases in humans. It is therefore important to understand the fundamental molecular genetics of development. We have discovered a novel human gene, termed S52, and its equivalent gene in the mouse. The predicted protein derived from these genes would indicate that S52 protein may interact with other proteins, possibly nerve growth factors, in the body to regulate normal development an ....Developmentally regulated genes when mutated or deleted can cause a variety of diseases including neurological diseases in humans. It is therefore important to understand the fundamental molecular genetics of development. We have discovered a novel human gene, termed S52, and its equivalent gene in the mouse. The predicted protein derived from these genes would indicate that S52 protein may interact with other proteins, possibly nerve growth factors, in the body to regulate normal development and possibly facilitate the survival of nerve cells in embryos. Strikingly, the worm C. elegans, an evoluationary very distant animal, also has a very similar gene to human. The fact that the protein has been so conserved throughout evolution supports the idea that S52 function is important in development. S52 mRNA is expressed in the developing brain, particularly in a special group of cells called the floor plate. Floor plate is a tissue that has ability to organize the patterning and differentiation of cells within the developing brain. S52 is also expressed in motor neurons in early stages of development and later in a subset of dorsal spinal cord neurons. We have mapped S52 to the short arm of human chromosome 2 (2p15-22). This region of chromosome 2 is linked to several human genetic diseases with neurological defects. Based on our preliminary data, we think S52 is not only important for normal brain development but may be mutated in a human neurological disease called Spastic Paraplegia Type 4 (SPG4) which is characterized by a degeneration of nerve cells in the spinal cord. The aim of this project is to further our understanding of the function of this gene and investigate its role in disease. This knowledge will contribute to an overall increase in our understanding of the molecular basis of brain development and neurological disease in humans.Read moreRead less
Antecedents Of Renal Disease In Aboriginal Children And Young Adults - 12 Year Follow-up
Funder
National Health and Medical Research Council
Funding Amount
$1,845,061.00
Summary
Aboriginal Australians have 2 to 10 times the rate of chronic kidney disease and premature death from cardiovascular disease compared with non-Aboriginal Australians. Our 6 year follow-up of Aboriginal children from diverse NSW areas has shown no increase in risk for these diseases when compared with non-Aboriginal children. The ARDAC Second Phase Study will follow the participants for another 6 years to determine whether these health disparities start to manifest in young Aboriginal adults.
Function Of The Lysophospholipid Receptor Family In Neuronal Stem Cells And Their Progenitors.
Funder
National Health and Medical Research Council
Funding Amount
$380,723.00
Summary
Stem cells have the potential to give rise to a vast array of differentiated cells. Neuronal stem cells (NSC) can differentiate into progenitor cells which can themselves differentiate into cells of the nervous system: neurons and macroglial cells (astrocytes, oligodendrocytes, Schwann cells). This in turn can assist in the treatment of degenerative diseases such as multiple sclerosis, Parkinson's disease, motoneuron desease etc. Our project aims to study the effects on NSC and their progenitor ....Stem cells have the potential to give rise to a vast array of differentiated cells. Neuronal stem cells (NSC) can differentiate into progenitor cells which can themselves differentiate into cells of the nervous system: neurons and macroglial cells (astrocytes, oligodendrocytes, Schwann cells). This in turn can assist in the treatment of degenerative diseases such as multiple sclerosis, Parkinson's disease, motoneuron desease etc. Our project aims to study the effects on NSC and their progenitor cells of the lysophospholipids lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P), bioactive molecules known to play an essential role in the nervous system during development and inflammation. Our project aims to understand the mechanisms of action of these molecules in NSC maintenance, proliferation, differentiation and migration. By understanding how these molecules are able to regulate NSC biology will provide new avenues in the development of tools necessary for stem cell therapy.Read moreRead less
Regulation Of The Drosophila C-Myc Homologue In Stem Cell Growth And Division.
Funder
National Health and Medical Research Council
Funding Amount
$613,397.00
Summary
The mechanisms controlling stem cell growth and division require elucidation if we are to use stem cells in regenerative medicine and find cancer treatments. Due to experimental limitations such mechanisms are largely unknown in humans. We aim to use the vinegar fly as a model system to understand the importance of microenvironment to cancer gene control in stem cells. We will identify the secreted signals, from the neighbouring cells, required to control cancer initiation in stem cells.