How do interactions between axon guidance molecules bring about directed axon growth? This project deals with a fundamental, yet poorly understood biological problem at the cutting edge of international science - how axons navigate to their targets. A better understanding of this basic biological process will greatly assist the development of therapies to treat a wide range of clinical conditions in which axonal connections between neurons are disrupted by trauma or disease.
Molecular genetic analyses of trinucleotide repeat expansions. Several neuronal diseases like Huntington's disease, Frederick's ataxia and fragile X syndrome are caused by expansion of trinucleotide repeat sequences in the deoxyribonucleic acid (DNA). These diseases show progressive severity in subsequent generations. Here we use a simple plant model with a very similar DNA mutation to study the genetic basis of repeat expansions over several generations across populations. This proposal will im ....Molecular genetic analyses of trinucleotide repeat expansions. Several neuronal diseases like Huntington's disease, Frederick's ataxia and fragile X syndrome are caused by expansion of trinucleotide repeat sequences in the deoxyribonucleic acid (DNA). These diseases show progressive severity in subsequent generations. Here we use a simple plant model with a very similar DNA mutation to study the genetic basis of repeat expansions over several generations across populations. This proposal will improve our mechanistic understanding of genetic diseases in populations. In addition, this proposal is expected to lead to identification of potential targets and technologies that would be of interest to Australian industry.Read moreRead less
The role of the neuronal Hu proteins in the regulation of the BMP signalling pathway. We aim to understand the critical decision of a neural progenitor to commit to becoming a neuron. The BMP signalling pathway is central in this decision. Neural progenitors appear to become insensitive to BMP signals, and this lack of signalling leads to neuronal differentiation. We hypothesise that neuronal identity is regulated by an unusual genetic switch- the translational regulation by the neuronal Hu pr ....The role of the neuronal Hu proteins in the regulation of the BMP signalling pathway. We aim to understand the critical decision of a neural progenitor to commit to becoming a neuron. The BMP signalling pathway is central in this decision. Neural progenitors appear to become insensitive to BMP signals, and this lack of signalling leads to neuronal differentiation. We hypothesise that neuronal identity is regulated by an unusual genetic switch- the translational regulation by the neuronal Hu proteins of two proteins in the BMP pathway. Verification of a post-transcriptional regulatory mechanism for cell fate determination would be a major discovery, and may prompt investigation of how to harness the neuron-inducing function of the Hu proteins to address the therapeutic need for new neurons in neurologic diseases.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668266
Funder
Australian Research Council
Funding Amount
$264,000.00
Summary
High Resolution Cellular and Molecular Imaging System. Understanding where molecules are within cells, and how they interact with each other, is fundamental to significant advances being made in biology. Our research will use advanced imaging techniques to localize proteins within a variety of cells including neurons and germ cells. We will be able to determine how the different molecules within a single cell interact with each other. This information is relevant to many biological mechanisms ....High Resolution Cellular and Molecular Imaging System. Understanding where molecules are within cells, and how they interact with each other, is fundamental to significant advances being made in biology. Our research will use advanced imaging techniques to localize proteins within a variety of cells including neurons and germ cells. We will be able to determine how the different molecules within a single cell interact with each other. This information is relevant to many biological mechanisms and to many human diseases. Furthermore, our research will help maintain Australia's strong international reputation in the fields of neuroscience, protein trafficking and stem cells. Read moreRead less
Truncating presenilin mutations and their effects on gamma-secretase activity, tau and beta-catenin - insights into Alzheimers disease and cancer. Cancer and dementia are primarily afflictions of the aged and are increasingly important in an aging Australian population. 95% of all Alzheimer's disease is spontaneous (not inherited) but we know little about the molecular mechanisms underlying it. Our discovery that truncated presenilin proteins potently inhibit normal protein function suggests tha ....Truncating presenilin mutations and their effects on gamma-secretase activity, tau and beta-catenin - insights into Alzheimers disease and cancer. Cancer and dementia are primarily afflictions of the aged and are increasingly important in an aging Australian population. 95% of all Alzheimer's disease is spontaneous (not inherited) but we know little about the molecular mechanisms underlying it. Our discovery that truncated presenilin proteins potently inhibit normal protein function suggests that changes in presenilin function in aged cells might be a common molecular link between spontaneous and inherited Alzheimer's disease and could contribute to frontotemporal dementia and cancer. Our research will show whether this phenomenon might provide a breakthrough in our understanding of these diseases and be a productive area for research into their amelioration and/or prevention.Read moreRead less
Gene Discovery and Functional Analysis of Copper Homeostasis Genes in Drosophila. Copper is a vital nutrient required for the formation and maintenance of bones, blood vessels and the central nervous system, but copper is also potentially toxic when in excess. Homeostatic mechanisms are needed to maintain safe levels of copper in the body and disruptions to these mechanisms are associated with disorders such as Alzheimer's disease, heart disease and osteoporosis. We are investigating the regulat ....Gene Discovery and Functional Analysis of Copper Homeostasis Genes in Drosophila. Copper is a vital nutrient required for the formation and maintenance of bones, blood vessels and the central nervous system, but copper is also potentially toxic when in excess. Homeostatic mechanisms are needed to maintain safe levels of copper in the body and disruptions to these mechanisms are associated with disorders such as Alzheimer's disease, heart disease and osteoporosis. We are investigating the regulation of a key copper pump, the Menkes protein, which helps control copper levels in the body and we are using the genetic advantages of the fruit fly Drosophila to discover new genes that regulate Menkes activity and therefore copper levels. These studies could lead to novel therapies for a range of copper-related disorders.Read moreRead less
Identification and characterisation of caspase inhibitors. Organisms use a tightly controlled process of cell death (termed apoptosis) to remove dangerous and unwanted cells. Dysregulation of this process can contribute to diseases such as cancer and autoimmune disease. Caspases are protease effectors of apoptosis. Regulation of their activity is vital for effective control of cell survival and death. Using a functional screening system invented by the 1st CI, we aim to isolate and characterise ....Identification and characterisation of caspase inhibitors. Organisms use a tightly controlled process of cell death (termed apoptosis) to remove dangerous and unwanted cells. Dysregulation of this process can contribute to diseases such as cancer and autoimmune disease. Caspases are protease effectors of apoptosis. Regulation of their activity is vital for effective control of cell survival and death. Using a functional screening system invented by the 1st CI, we aim to isolate and characterise novel inhibitors of caspases. Such inhibitors may in time be used as targets for development of therapeutic or diagnostic reagents aimed at manipulating the apoptotic process to diagnose, prevent or treat disease.Read moreRead less