Solving the puzzle of complex disease - genes and their interactions with the environment. Many human diseases are caused by the interplay of genetic predisposition (nature) and the environment (nurture); but their causes remain a mystery, since much past research has focused on these aspects in isolation. This project will aim to better understand these complex diseases using a multi-factorial approach that brings both nature and nurture together.
Defining the Molecular Targets of Evolution. With significant advances in next-generation sequencing technologies we now have the genomes of hundreds vertebrate species, but understanding how the differences and similarities within these genomes control species diversity is largely unknown. The similarity in skull shape between the thylacine and dogs coupled with their deep ancestry, having last shared a common ancestor over 160 million years ago, provides an unprecedented opportunity to examine ....Defining the Molecular Targets of Evolution. With significant advances in next-generation sequencing technologies we now have the genomes of hundreds vertebrate species, but understanding how the differences and similarities within these genomes control species diversity is largely unknown. The similarity in skull shape between the thylacine and dogs coupled with their deep ancestry, having last shared a common ancestor over 160 million years ago, provides an unprecedented opportunity to examine how evolution works at the DNA level. This proposal will determine if animals that develop identical skull shapes, also show identical changes in their DNA. The findings will define new developmental genes and explain how selection, adaptation and evolution works at the DNA level. Read moreRead less
Genetics of Postmenopausal Bone Loss. The major consequence of bone loss in our ageing society is fracture. At 50 years for women, the lifetime risk of sustaining an osteoporotic fracture is 50%. The consequences of these fractures, which can include reduced life expectancy, prolonged medical care, and loss of independence, have a profound socioeconomic impact in an ageing population. The proposed study offers a unique opportunity to examine the contribution of genetic factors to postmenopausal ....Genetics of Postmenopausal Bone Loss. The major consequence of bone loss in our ageing society is fracture. At 50 years for women, the lifetime risk of sustaining an osteoporotic fracture is 50%. The consequences of these fractures, which can include reduced life expectancy, prolonged medical care, and loss of independence, have a profound socioeconomic impact in an ageing population. The proposed study offers a unique opportunity to examine the contribution of genetic factors to postmenopausal osteoporosis.Read moreRead less
Using mouse genetics to understand skin development and cell biology. During embryonic development the skin forms a protective barrier which permits life outside the womb and provides a window into the biology of cells. This project aims to use the skin to identify and characterise genes necessary for embryonic development and maintenance, the development of diseases and to explore their broader roles in other organs.
Genetic regulation of wing reduction in the emu. This project aims to examine the genetic mechanisms that generate limb diversity, using wing reduction in the emu as a model. A hot topic in biology at present is evolutionary developmental biology, or how genes control morphological diversity. This project will explore the functions of two novel genes implicated in wing reduction. The project expects to expand knowledge in the area of developmental biology, and limb morphogenesis specifically. It ....Genetic regulation of wing reduction in the emu. This project aims to examine the genetic mechanisms that generate limb diversity, using wing reduction in the emu as a model. A hot topic in biology at present is evolutionary developmental biology, or how genes control morphological diversity. This project will explore the functions of two novel genes implicated in wing reduction. The project expects to expand knowledge in the area of developmental biology, and limb morphogenesis specifically. It will bear upon the phylogeny of flightlessness among birds. It also has potential implications for studying human limb deformities. Overall, the project will enhance our understanding of how genes control the great diversity that we see in nature.Read moreRead less
Ageing and the muscle stem cell niche. Adult stem cells are critical for repair and maintenance of tissues and ageing tissues show reduced stem cell function. This project will focus on how ageing leads to disruption of communication between muscle stem cells and their niche. The project aims to identify new therapeutic targets for age-related muscle wasting and reduced mobility in the elderly.
Identifying Novel Genes Causing Cytochrome C Oxidase (COX) Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$426,917.00
Summary
Our bodies convert food into energy in tiny cellular power plants called mitochondria. Each year about 50 Australian children inherit disorders of mitochondrial energy generation. The most severe disorders cause infant death, while others cause degenerative diseases in later life, particularly affecting brain and muscle. In most cases we lack effective treatments. The genetic causes of mitochondrial disorders are incredibly diverse, with over 70 disease genes known. Some are located on the uniqu ....Our bodies convert food into energy in tiny cellular power plants called mitochondria. Each year about 50 Australian children inherit disorders of mitochondrial energy generation. The most severe disorders cause infant death, while others cause degenerative diseases in later life, particularly affecting brain and muscle. In most cases we lack effective treatments. The genetic causes of mitochondrial disorders are incredibly diverse, with over 70 disease genes known. Some are located on the unique mitochondrial DNA we inherit only from our mothers. Many more genes await discovery. This study focuses on the mitochondrial disorder cytochrome c oxidase (COX) deficiency, for which we have diagnosed 80 Australian patients. COX requires 13 separate components to be assembled together in order to work properly, but mutations in the genes encoding these components are not present in most patients. We believe that the most common problems will be in genes involved in assembling the components rather than in the components themselves. We will use a number of methods to pinpoint where in the genome the disease genes are located. A key to our strategy is identifying patients likely to have mutations in the same gene. We have identified two such groups, and will do studies that involving fusing two cell lines together to confirm they have the same disorder. We will then perform genetic mapping to look for regions of similarity in the genome using DNA (SNP) chips. We will test how well the genes in such regions are expressed, whether we can correct the problem in cultured skin cells by introducing a healthy copy of that chromosome, and look for gene mutations. Identifying these genes will allow us to improve future diagnosis and prevention and may allow us to develop new methods of treatment. Milder mitochondrial problems also contribute to a range of more common diseases such as diabetes and Alzheimer disease, so any new treatments could potentially have wide applicationRead moreRead less
The role of Roquin in microRNA function and decay. The aim of this study is to understand how microRNAs (newly discovered genetic components that control cell growth and survival) function and are regulated. The expected discoveries will help understand how common cancers including breast cancer and autoimmune diseases emerge, and will help develop cutting edge genetic technologies.
Genetic Variation Of Mitochondrial Complex I: Its Role In Rare And Common Diseases
Funder
National Health and Medical Research Council
Funding Amount
$628,415.00
Summary
Our bodies convert food into energy in tiny cellular power plants called mitochondria. Each year about 50 Australian children inherit disorders of mitochondrial energy generation. The most severe disorders cause infant death, while others cause degenerative diseases in later life, particularly affecting brain and muscle. In most cases we lack effective treatments. The genetic causes of mitochondrial disorders are incredibly diverse, with over 70 disease genes known. Some are located on the uniqu ....Our bodies convert food into energy in tiny cellular power plants called mitochondria. Each year about 50 Australian children inherit disorders of mitochondrial energy generation. The most severe disorders cause infant death, while others cause degenerative diseases in later life, particularly affecting brain and muscle. In most cases we lack effective treatments. The genetic causes of mitochondrial disorders are incredibly diverse, with over 70 disease genes known. Some are located on the unique mitochondrial DNA we inherit only from our mothers. Many more genes await discovery. This grant focuses on the most common energy generation disorder, known as Complex I deficiency. Complex I requires 46 separate components to be assembled together in order to work properly, but mutations in the 46 genes encoding these components only seem to explain disease in about half of all patients. Our aim is to identify new disease genes and to determine whether some patients have mutations in two different genes that interact to cause disease, rather than in a single gene. We will use a number of methods to pinpoint where in the genome the causative genes are located and then home in on the exact changes in the genes that cause disease. Identifying these genes will allow us to improve future diagnosis and prevention of mitochondrial disease. We will also generate mice in which one of the Complex I genes has been knocked out. These mice will allow us to better understand the basic disease mechanisms that link gene changes to disease. Understanding the basic biology may allow us to develop new methods of treatment. The mouse models will also be useful for trialling new treatments and for investigating the role of milder mitochondrial problems in common diseases such as diabetes and Parkinson disease. Any new treatments could potentially have wide application.Read moreRead less