Molecular Genetics Of The Host Response Defect In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$564,690.00
Summary
Cystic fibrosis is the most common lethal genetic disease in Caucasian populations. Affected individuals suffer from a number of symptoms but the most serious is a chronic infect with the bacterial pathogen Pseudomonas aeruginosa. The sustained lung inflammation caused by infection with Pseudomonas aeruginosa ultimately destroys the structure of the lung to the point where it can no longer function. Gene therapy has been suggested as a possible treatment for the disease but another approach is t ....Cystic fibrosis is the most common lethal genetic disease in Caucasian populations. Affected individuals suffer from a number of symptoms but the most serious is a chronic infect with the bacterial pathogen Pseudomonas aeruginosa. The sustained lung inflammation caused by infection with Pseudomonas aeruginosa ultimately destroys the structure of the lung to the point where it can no longer function. Gene therapy has been suggested as a possible treatment for the disease but another approach is to identify the CF specific aspects of the inflammatory response and target those for therapeutic development. In our previous work we have identified several strong candidates for the inflammatory molecules in the CF lung and in this application we will test those candidates to see whether they play a major role in CF lung disease.Read moreRead less
The genetic basis of leaf lamina establishment and growth. This study will help reveal how the development of leaves is coordinated by tissue patterning genes and the plant growth hormone auxin. All plants grow in this way, and the findings, made using a model laboratory plant, will be applicable to crop species as well.
Microarray-targeted Candidate Gene Approach To Finding Ovarian Cancer Susceptibility Genes
Funder
National Health and Medical Research Council
Funding Amount
$612,933.00
Summary
We propose that subtle, heritable changes in the expression or function of genes that are switched off, or on, early in the development of ovarian tumours, may predispose the individual to ovarian cancer. We will are carry out a large study of the most common subtype of ovarian adenocarcinoma, serous invasive tumors, in order to identify genes that affect a woman's risk of ovarian cancer. Identification of women at elevated risk for ovarian cancer on the basis of their genotype will allow them t ....We propose that subtle, heritable changes in the expression or function of genes that are switched off, or on, early in the development of ovarian tumours, may predispose the individual to ovarian cancer. We will are carry out a large study of the most common subtype of ovarian adenocarcinoma, serous invasive tumors, in order to identify genes that affect a woman's risk of ovarian cancer. Identification of women at elevated risk for ovarian cancer on the basis of their genotype will allow them to be targeted for screening, and for intervention studies, as well as providing fundamental insight into the etiology of ovarian cancer.Read moreRead less
Understanding the evolution of the alternation of generations in the land plant life cycle. This project will investigate the genetic basis and evolution of the land plant life cycle, in which both haploid and diploid phases consist of complex multicellular bodies. The project's findings, which will be made using two model laboratory plants, will be applicable to all plants and will help understand important processes such as pollen and seed production.
Molecular mechanisms that generate muscle cell type diversity. The general aim of this project is to exploit the advantages of the zebrafish system and our access to the embryology of Australian shark species to generate an understanding of the basis for muscle fibre diversity and evolution. While there is some understanding of the fundamental genetic basis of how to make an individual muscle cell from a nascent myoblast there is far less knowledge on how individual muscle cells generate mature ....Molecular mechanisms that generate muscle cell type diversity. The general aim of this project is to exploit the advantages of the zebrafish system and our access to the embryology of Australian shark species to generate an understanding of the basis for muscle fibre diversity and evolution. While there is some understanding of the fundamental genetic basis of how to make an individual muscle cell from a nascent myoblast there is far less knowledge on how individual muscle cells generate mature muscle types and patterns. The intended outcome of this research is to generate understanding of the complex molecular basis of muscle patterning in the simple paradigm of the zebrafish myotome that could be applied across the vertebrate phylogeny.Read moreRead less
Development and evolution of land plant shoots. How do plants grow and develop their wonderful diversity of forms, from cereal crops to eucalypt forests? The project aims to understand basic mechanisms of plant development via comparative studies using the model angiosperm, Arabidopsis, and the liverwort, Marchantia, which possesses a simplified genome. Comparative studies of the genetic basis of the body plan, branching, and hormonal action could unlock their evolutionary elaboration from the s ....Development and evolution of land plant shoots. How do plants grow and develop their wonderful diversity of forms, from cereal crops to eucalypt forests? The project aims to understand basic mechanisms of plant development via comparative studies using the model angiosperm, Arabidopsis, and the liverwort, Marchantia, which possesses a simplified genome. Comparative studies of the genetic basis of the body plan, branching, and hormonal action could unlock their evolutionary elaboration from the simpler liverworts to more complex flowering plants. The project may generate new understanding of the principles of how genes and hormones control the architecture of plant shoot systems, and support the targeted selection of new agricultural plants.Read moreRead less
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
The integration of physical and genetic signals in cardiac development. The patterning of the heart is a highly complicated process. This project will investigate how blood flow through the heart, as a result of heart function, is important in stimulating the formation of structures within the heart and changes in the shape of the heart as it grows.
Mobile DNA activity in the mammalian primordial germline. Early in pregnancy, a handful of cells in the embryo become primordial germ cells (PGCs). These PGCs will eventually give rise to sperm or egg cells, representing a critical inter-generational genetic link. Mobile DNA sequences target PGCs to create new heritable genetic changes. This proposal aims to analyse the activity, regulation, and consequences of mobile DNA activity in PGCs. This project expects to generate significant knowledge a ....Mobile DNA activity in the mammalian primordial germline. Early in pregnancy, a handful of cells in the embryo become primordial germ cells (PGCs). These PGCs will eventually give rise to sperm or egg cells, representing a critical inter-generational genetic link. Mobile DNA sequences target PGCs to create new heritable genetic changes. This proposal aims to analyse the activity, regulation, and consequences of mobile DNA activity in PGCs. This project expects to generate significant knowledge about the origins of mammalian genetic diversity. Expected outcomes include enhanced national and international collaborations across disciplines and new experimental systems. The expected benefit is an enhanced understanding of the mutational processes underlying genetic diversity and disease in mammals.Read moreRead less
Old genes learning new tricks: characterising regulatory changes driving increased heart complexity during vertebrate evolution. The heart has dramatically increased in morphological complexity during vertebrate evolution but the molecular basis driving these major changes remains unknown. Using comparative genomics approaches, this project will explore changes in the regulation of genes involved in heart formation that lead to changes in cardiac structure. It will elucidate for the first time t ....Old genes learning new tricks: characterising regulatory changes driving increased heart complexity during vertebrate evolution. The heart has dramatically increased in morphological complexity during vertebrate evolution but the molecular basis driving these major changes remains unknown. Using comparative genomics approaches, this project will explore changes in the regulation of genes involved in heart formation that lead to changes in cardiac structure. It will elucidate for the first time the cardiac regulatory repertoire in zebrafish and will compare it with that of fly and mouse using cutting-edge bioinformatics pipelines. This work will unravel cardiac-specific regulatory modifications that give rise to evolutionary changes. On a broader scale, it will shed new light on the role of regulatory innovations over gene innovations in the emergence of new traits.Read moreRead less