Australian Laureate Fellowships - Grant ID: FL170100008
Funder
Australian Research Council
Funding Amount
$3,248,822.00
Summary
Genes, reproduction and inheritance in a microbe. The project aims to particularly explore sexual gene inheritance in Plasmodium, a representative of a large group of human and animal parasites. Plasmodium must have a sexual exchange of genes in the mosquito for the transfer of disease to a new host. This project will investigate the fate and behaviour of Plasmodium genes during reproduction; the differing chromosome states resulting from sexual genetic processes and the asymmetrical inheritance ....Genes, reproduction and inheritance in a microbe. The project aims to particularly explore sexual gene inheritance in Plasmodium, a representative of a large group of human and animal parasites. Plasmodium must have a sexual exchange of genes in the mosquito for the transfer of disease to a new host. This project will investigate the fate and behaviour of Plasmodium genes during reproduction; the differing chromosome states resulting from sexual genetic processes and the asymmetrical inheritance of some Plasmodium genes. The project is expected to advance Australia’s ability to understand the reproduction and survival of these parasites in their mosquito vector and develop cutting-edge genetic tools that will advance the microbial genetics discipline globally. This may ultimately lead to biotechnology and biomedical outcomes.Read moreRead less
Further Genetic and Molecular studies of an Important Prokaryotic Regulator Protein TyrR. Genomes encode many functions whose expression varies dramatically depending on particular cellular environments. Special proteins called Regulator Proteins act as sensors to detect subtle changes in the environment and, in response, to influence the expression of certain genes either dampening them down or stimulating their activity. We are working with the TyrR regulator protein of the simple bacterium E ....Further Genetic and Molecular studies of an Important Prokaryotic Regulator Protein TyrR. Genomes encode many functions whose expression varies dramatically depending on particular cellular environments. Special proteins called Regulator Proteins act as sensors to detect subtle changes in the environment and, in response, to influence the expression of certain genes either dampening them down or stimulating their activity. We are working with the TyrR regulator protein of the simple bacterium Escherichia coli to elucidate the molecular strategies used in these controls. Because this protein controls the expression of a number of genes with diverse functions, evolution has selected equally diverse mechanisms to achieve appropriate transcriptional responses. The detailed knowledge of the E.coli genome and of the various genes regulated by TyrR make it an excellent system for such fundamental studies.Read moreRead less
The role of dysregulated signalling by TORC1 in mitochondrial disease. The mitochondria are tiny subcellular compartments responsible for producing over 90 per cent of the cell's energy. Mitochondrial defects feature both in genetic diseases that directly affect the mitochondria and in most neurodegenerative diseases. These incurable diseases are expected to eclipse cancer as the second major cause of death worldwide by 2040. Using a simple model organism, Dictyostelium, previous research showed ....The role of dysregulated signalling by TORC1 in mitochondrial disease. The mitochondria are tiny subcellular compartments responsible for producing over 90 per cent of the cell's energy. Mitochondrial defects feature both in genetic diseases that directly affect the mitochondria and in most neurodegenerative diseases. These incurable diseases are expected to eclipse cancer as the second major cause of death worldwide by 2040. Using a simple model organism, Dictyostelium, previous research showed that dysregulated intracellular signalling by a cellular energy-sensing alarm protein is responsible for diverse cellular pathologies in mitochondrially diseased cells. This project will determine the role in these pathways of a second cellular stress-sensing protein complex, TORC1. New treatment possibilities may emerge.Read moreRead less
Genomic and molecular characterisation of a novel Australian leishmania pathogen. Leishmaniasis is the second most serious protozoal disease after malaria. This project will help characterise the first Leishmania species identified in Australia providing molecular tools to monitor the pathogen and a detailed assessment of any potential risk to human health. Comparative analysis with more pathogenic species will help identify genes and mechanisms that determine the progression of human disease le ....Genomic and molecular characterisation of a novel Australian leishmania pathogen. Leishmaniasis is the second most serious protozoal disease after malaria. This project will help characterise the first Leishmania species identified in Australia providing molecular tools to monitor the pathogen and a detailed assessment of any potential risk to human health. Comparative analysis with more pathogenic species will help identify genes and mechanisms that determine the progression of human disease leading to the potential identification of new drug and vaccine targets. The methodologies and expertise developed will be used will be available to other research groups working on infectious diseases.Read moreRead less
Molecular genetic analysis of genes controlling morphogenesis: Dimorphic switching in the fungus Penicillium marneffei. Fungi exist in two predominant growth forms; unicellular yeast and multicellular mould (filamentous hyphae). Some fungi can alternate between these two forms in response to environmental stimuli, a process known as dimorphic switching. The cells of these two forms have distinctive shapes and physiological capacities established by genome-wide expression patterns that are trigge ....Molecular genetic analysis of genes controlling morphogenesis: Dimorphic switching in the fungus Penicillium marneffei. Fungi exist in two predominant growth forms; unicellular yeast and multicellular mould (filamentous hyphae). Some fungi can alternate between these two forms in response to environmental stimuli, a process known as dimorphic switching. The cells of these two forms have distinctive shapes and physiological capacities established by genome-wide expression patterns that are triggered by signalling pathways. This research aims to understand the fundamental mechanisms controlling dimorphic switching using Penicillium marneffei, a model system. P. marneffei switches between yeast and filamentous forms in response to temperature. Uncovering the molecular mechanisms that control dimorphic switching has important implications for biotechnology and medicine.Read moreRead less
Regulation of nuclear localisation of the AreA transcription factor in Aspergillus nidulans. An understanding of the means by which the expression of genes is regulated is of fundamental significance. Changes in gene expression are central to the development, growth and viability of all cells and their response to environmental changes/stresses. This study uses the fungus Aspergillus nidulans as an excellent molecular genetic tool to investigate how a key regulatory protein controls gene expres ....Regulation of nuclear localisation of the AreA transcription factor in Aspergillus nidulans. An understanding of the means by which the expression of genes is regulated is of fundamental significance. Changes in gene expression are central to the development, growth and viability of all cells and their response to environmental changes/stresses. This study uses the fungus Aspergillus nidulans as an excellent molecular genetic tool to investigate how a key regulatory protein controls gene expression in response to nitrogen starvation stress. Our understanding of these dynamic processes informs our approaches to the development of cancer therapies, to commercial biotechnology application and to control of human, plant and animal pathogens in which the infectious process is triggered by environmental stress. Read moreRead less
Molecular Genetic Analysis of Genes Regulating Metabolism in the Fungus Aspergillus nidulans. Filamentous fungi can use a wide variety of sources of carbon and nitrogen. In order to grow on these compounds metabolism is adjusted in response to changes in nutrient availability. Patterns of genome expression are altered by signalling to global regulatory genes which control the transcription of genes producing enzymes appropriate to the substrates available. This is of fundamental significance to ....Molecular Genetic Analysis of Genes Regulating Metabolism in the Fungus Aspergillus nidulans. Filamentous fungi can use a wide variety of sources of carbon and nitrogen. In order to grow on these compounds metabolism is adjusted in response to changes in nutrient availability. Patterns of genome expression are altered by signalling to global regulatory genes which control the transcription of genes producing enzymes appropriate to the substrates available. This is of fundamental significance to the physiology and development of fungi which include devastating pathogens and species used in industrial microbiology. This project aims to use the excellent molecular genetics of the model fungus Aspergillus nidulans to investigate the strategies employed and the mechanisms involved.Read moreRead less
Developmental genetics of malaria parasites. This project aims to improve our understanding of malarial genetics. The sexual cycle of malaria parasites occurs in mosquitoes. After sex, parasite progeny multiply to form infective spores that are injected into people by mosquito bite. Development of male and female malaria parasite gametes and their fusion to produce a diploid zygote are well understood, but the subsequent process of meiosis, development of a cyst stage and the sporogenic process ....Developmental genetics of malaria parasites. This project aims to improve our understanding of malarial genetics. The sexual cycle of malaria parasites occurs in mosquitoes. After sex, parasite progeny multiply to form infective spores that are injected into people by mosquito bite. Development of male and female malaria parasite gametes and their fusion to produce a diploid zygote are well understood, but the subsequent process of meiosis, development of a cyst stage and the sporogenic process to create haploid progeny for new infections are poorly understood in molecular genetic terms. The project aims to dissect the unique genetics of these insect stages using a rodent malaria model to generate crosses of different malaria parasite lines to determine when recombination takes effect.Read moreRead less
Metabolic control of gene expression networks and microbiome interactions. The proposal aims to advance our understanding of how metabolism (and resulting metabolites) regulate the expression of genes, and investigate how these processes dictate the interaction of microbiota with the immune system. The project is expected to generate transformative knowledge of gene regulation, a fundamental process for cellular function, and decipher how the microbiome yeast Candida albicans interacts with immu ....Metabolic control of gene expression networks and microbiome interactions. The proposal aims to advance our understanding of how metabolism (and resulting metabolites) regulate the expression of genes, and investigate how these processes dictate the interaction of microbiota with the immune system. The project is expected to generate transformative knowledge of gene regulation, a fundamental process for cellular function, and decipher how the microbiome yeast Candida albicans interacts with immune cells and bacteria. By utilising a powerful combination of molecular and systems biology with molecular genetics and imaging, the project outcomes should foster interdisciplinary collaborations and build capacity for fundamental and applied research to benefit academia and industry, locally and globally.Read moreRead less
Genetic and epigenetic control of developmental competence. Development is an important biological process of life and understanding development has important medical and economic benefits for Australia. This research aims to study development using a simple, easily manipulated and well established experimental organism, a fungus, as a model for development in other organisms, including humans. In addition, fungi directly impact on life at many levels. Fungi can be pathogens of humans, other ani ....Genetic and epigenetic control of developmental competence. Development is an important biological process of life and understanding development has important medical and economic benefits for Australia. This research aims to study development using a simple, easily manipulated and well established experimental organism, a fungus, as a model for development in other organisms, including humans. In addition, fungi directly impact on life at many levels. Fungi can be pathogens of humans, other animals or plants significantly affecting our health, agriculture and industry. Fungi are also beneficial to other organisms, especially to many plants, and are used to manufacture pharmaceuticals and enzymes used in the health and biotechnology industries.Read moreRead less