How Alzheimers-associated Cytoskeletal Inclusions Form Road Blocks And Impair Trafficking In Neurons
Funder
National Health and Medical Research Council
Funding Amount
$351,181.00
Summary
This research is aimed at delineating basic mechanisms of nerve cell dysfunction relevant to Alzheimer's disease and other dementias with the goal of achieving a positive impact into understanding the causes of these diseases. The outcomes of the project will identify pathways involved in generating pathological changes in nerve cells and will therefore facilitate the development of targeted therapies, ultimately improving the outlook for Alzheimer's patients and the community.
Functional Genomic Analyses Of Mitochondrial Disorders
Funder
National Health and Medical Research Council
Funding Amount
$577,001.00
Summary
Mitochondria produce most of the energy required by our bodies. Mutations in genes that make mitochondrial proteins cause mitochondrial dysfunction and lead to neurodegenerative and muscular diseases. We will identify mutations in mitochondrial genes in members of different Bulgarian and Gypsy families and discovery the mechanisms by which the mutations lead to disease.
Regulation Of RNA Processing In The Mitochondrial Disease MELAS
Funder
National Health and Medical Research Council
Funding Amount
$520,977.00
Summary
Mitochondria are microscopic, energy producing machines that are found in all human cells. Mitochondria contain a small set of genes that must work properly to make the energy our bodies require for health. Defects in the expression of mitochondrial genes cause debilitating diseases for which there are currently no cures. We have developed a new set of technologies that will be applied to understand how these mutations cause disease and provide insights into possible treatments.
Systems Approaches To Understanding The Assembly Of Mitochondrial Machines
Funder
National Health and Medical Research Council
Funding Amount
$600,005.00
Summary
Mitochondria produce the energy for our bodies. Defects in this process cause mitochondrial disease, which affects at least 1/5000 people. Diagnosis is often inconclusive as we do not understand the function of many proteins important in mitochondrial energy production. State of the art CRISPR gene-editing tools will be coupled with advanced proteomics techniques to model different types of mitochondrial disease and identify the functions of new candidate disease genes.
Targeting The Mitochondrial Transcriptome To Treat Mitochondrial Disease
Funder
National Health and Medical Research Council
Funding Amount
$456,836.00
Summary
Mitochondrial diseases are a diverse group of progressive and debilitating disorders for which there are no effective treatments. Furthermore it is currently impossible to apply gene therapy or RNA interference approaches to understand how mitochondria function or to treat mitochondrial diseases. We are developing a new technology that makes it possible to rationally manipulate mammalian mitochondrial RNAs for the first time, providing a unique approach for mitochondrial disease therapies.
Assembly And Misassembly Of Mitochondrial Respiratory Chain Complex I
Funder
National Health and Medical Research Council
Funding Amount
$520,520.00
Summary
Mitochondria are the powerhouses in our cells. They burn the carbon fuels we eat and store the energy by making ATP that is used for functions such as muscle contraction and triggering of nerves. Mitochondrial Complex I is a molecular motor that helps to make ATP. “Mitochondrial disease” is often seen when Complex I is not built properly and this results in early childhood death. In this project we will study how Complex I is built and how the mitochondria responds to assembly problems.
The Structure And Organization Of The Mitochondrial Genome In Health And Mitochondrial Disease
Funder
National Health and Medical Research Council
Funding Amount
$553,646.00
Summary
Mitochondrial DNA (mtDNA) mutations and mitochondrial dysfunction have been associated with a wide range of multi-system human diseases, although much remains to be learnt about molecular mechanisms in the pathogenesis of these diseases. Our goal is to understand how the expression of the mitochondrial DNA is regulated by mtDNA-binding proteins that will allow us to provide important insights into the molecular mechanisms of mitochondrial diseases.
OXPHOS Upregulation To Preserve Vision In Leber's Hereditary Optic Neuropathy
Funder
National Health and Medical Research Council
Funding Amount
$496,874.00
Summary
Leber's Hereditary Optic Neuropathy (LHON) is a devastating blinding disease that preferentially affects young men. Sufferers have normal vision until teenage years or their twenties when a rapid loss of vision occurs that results in permanent blindness. It is caused by genetic changes in the mitochondrial DNA that we inherit from our mothers. The mitochondria are the cells' energy generators. We aim to use molecules similar to female hormones to boost energy as a new treatment to preserve visio ....Leber's Hereditary Optic Neuropathy (LHON) is a devastating blinding disease that preferentially affects young men. Sufferers have normal vision until teenage years or their twenties when a rapid loss of vision occurs that results in permanent blindness. It is caused by genetic changes in the mitochondrial DNA that we inherit from our mothers. The mitochondria are the cells' energy generators. We aim to use molecules similar to female hormones to boost energy as a new treatment to preserve vision in at-risk LHON individuals.Read moreRead less
Mitochondrial Damage Following Fetal Hypoxia Or Birth Asphyxia: Using Creatine To Preserve Mitochondrial Function
Funder
National Health and Medical Research Council
Funding Amount
$838,726.00
Summary
There is a need for a therapy that can be given before a mother gives birth to protect the baby should ‘oxygen starvation’ threaten the baby’s brain and other organs such as the heart, kidney, lungs, and the ability to breathe properly. We are suggesting that an increased intake of creatine is a very effective treatment against this threat, and its proven safety and ease of use recommends it for wide application, particularly in countries where the access to medical resources is poor.
Transforming The Diagnosis Of Mitochondrial Disorders Using High-throughput Sequencing, Functional Prediction And Experimental Validation
Funder
National Health and Medical Research Council
Funding Amount
$670,794.00
Summary
The human genome project sparked enormous improvements in our ability to sequence DNA. “Next Generation” DNA sequencing can potentially sequence an individual’s entire genome in a week and has the ability to transform the diagnosis of inherited diseases but is as yet unproven in a medical genetics context. We will develop and validate the use of Next Generation sequencing to enable the rapid sequencing of over 1000 genes in which mutations cause inherited metabolic diseases.