Roles Of Impaired Apoptosis And Differentiation In Tumourigenesis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$21,656,910.00
Summary
The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remark ....The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remarkable cell suicide process termed apoptosis. Unfortunately, however, occasionally a random accident to the genes in one of our cells prevents the machinery for apoptosis from being turned on. In that case, the cell will not die when it should and, by continually dividing, it may eventually give rise to a cancer. Since most cancer cells still retain most of the machinery for apoptosis, however, a drug that could switch on this natural cell death machinery would provide a promising new approach to cancer therapy. Identifying and developing such drugs is one major long-term goal of this program. The other focus of our program concerns stem cells. These are rare cells with the remarkable ability to generate an entire tissue. For example, one of our laboratories has identified stem cells that can generate all the cells in the breast. The almost unlimited regenerative capacity of stem cells has a built-in danger. If a stem cell acquires the ability to proliferate excessively, it can go on to form a tumour. Indeed, many cancer researchers now suspect that rare stem cells within a tumour cause its inexorable growth. If tumour growth is maintained by stem cells, it will be essential to develop new forms of therapy that target these rare cancer stem cells rather than merely the bulk of the tumour cells. This is another key long-term goal of our program.Read moreRead less
Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behav ....Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behaviour of therapeutic stem cells introduced into the body.Read moreRead less
Taming the intruders: the domestication of Tigger transposable elements in mammals. It has become apparent that most of the DNA that makes us what we are is actually comprised of the remnants of invading parasitic DNA acquired over time. A continual battle exists between host which tries to silence or remove this DNA, and the parasite that tries to multiply and spread. We are currently investigating an intriguing aspect of this process that involves host genomes 'domesticating' parasitic DNA to ....Taming the intruders: the domestication of Tigger transposable elements in mammals. It has become apparent that most of the DNA that makes us what we are is actually comprised of the remnants of invading parasitic DNA acquired over time. A continual battle exists between host which tries to silence or remove this DNA, and the parasite that tries to multiply and spread. We are currently investigating an intriguing aspect of this process that involves host genomes 'domesticating' parasitic DNA to provide novel functions, thereby facilitating the evolution of specific characteristics within species.Read moreRead less
Role of mRNA polyadenylation control in gene expression. Several benefits would come from a more complete understanding of the function of the messenger RNA poly(A) tail. It is frequently targeted by mechanisms that control cellular protein synthesis. This is most evident in developmental biology, where tail length control regulates maternal mRNA expression. Our previous work suggests that it has much wider importance for cellular function than previously thought and thus its study will produce ....Role of mRNA polyadenylation control in gene expression. Several benefits would come from a more complete understanding of the function of the messenger RNA poly(A) tail. It is frequently targeted by mechanisms that control cellular protein synthesis. This is most evident in developmental biology, where tail length control regulates maternal mRNA expression. Our previous work suggests that it has much wider importance for cellular function than previously thought and thus its study will produce knowledge of broad relevance to modern life sciences and its applications in medicine and biotechnology. Finally, a better understanding of yeast cellular biology is of benefit to the food and biotechnology sector of industry.Read moreRead less
Adaptive Evolution of BRCA1 in Ancestral Mammals. This project investigates adaptive evolution of BRCA1 in the early radiation of mammals. We will test the hypothesis that the evolution of mammary glands and X chromosome inactivation has resulted in modification of the BRCA1 protein sequence as it aquired new roles in these processes. We will also investigate the importance of these changes inducing compensatory changes in other parts of the protein.
The Cytochrome P450 Gene Super-family in Drosophila melanogaster; Gene Function and Insecticide Resistance. The cytochrome P450 (Cyp) gene super-family is represented by over 90 sequences in the genome of the vinegar fly, Drosophila melanogaster. To date, four Cyp genes are found to be involved in insecticide resistance. The function of the majority of Cyp genes is unknown. This project will investigate the function and regulation of D. melanogaster Cyp genes, linking the fly's genotype to its ....The Cytochrome P450 Gene Super-family in Drosophila melanogaster; Gene Function and Insecticide Resistance. The cytochrome P450 (Cyp) gene super-family is represented by over 90 sequences in the genome of the vinegar fly, Drosophila melanogaster. To date, four Cyp genes are found to be involved in insecticide resistance. The function of the majority of Cyp genes is unknown. This project will investigate the function and regulation of D. melanogaster Cyp genes, linking the fly's genotype to its phenotype. By studying the effects of Cyp genes on fly survival, Cyp gene expression and regulation, and expressing selected Cyp genes in a yeast expression system, we will enhance our understanding of Cyp gene function and evolution.Read moreRead less
Discovering sex determining genes in a reptile with genetic and environmental sex determination. Reptile sex determination is particularly fascinating because it is triggered either by genes on sex chromosomes or by the nest temperature. This project will identify and characterise candidate sex determining genes in a model reptile to understand how genes control sexual differentiation and how they interact with temperature.
DNA methylation in insect social evolution. This project will investigate the evolutionary relationship between DNA methylation and the advanced sociality displayed by bees, ants and wasps. The project will map DNA methylation across the social insects and test whether it has coevolved with sociality. It will also determine how a vital social cue, the queen pheromone, influences the worker methylome. Finally, it will apply quantitative genetic and methylomic methods to wild insects, revealing pa ....DNA methylation in insect social evolution. This project will investigate the evolutionary relationship between DNA methylation and the advanced sociality displayed by bees, ants and wasps. The project will map DNA methylation across the social insects and test whether it has coevolved with sociality. It will also determine how a vital social cue, the queen pheromone, influences the worker methylome. Finally, it will apply quantitative genetic and methylomic methods to wild insects, revealing patterns of selection and inheritance in epigenetic and phenotypic traits. By combining genomic and evolutionary methods, the project will advance the ongoing debate about the importance of methylation to sociality and extreme phenotypic plasticity. It will contribute to a quantum leap in our understanding of DNA methylation and sociobiology and mark the first application of quantitative genetics to wild insects.Read moreRead less
ARC Centre of Excellence - Structural and Functional Microbial Genomics. The research falls under the National Research Priority Frontier Technologies for Building and Transforming Australian Industries, with the priority goal of frontier technologies. The research has commercial applications, such as the development of novel antimicrobials and vaccines, with potentially enormous impact in the biotechnology area of biomedical health and the primary industries. In addition, the project will use ....ARC Centre of Excellence - Structural and Functional Microbial Genomics. The research falls under the National Research Priority Frontier Technologies for Building and Transforming Australian Industries, with the priority goal of frontier technologies. The research has commercial applications, such as the development of novel antimicrobials and vaccines, with potentially enormous impact in the biotechnology area of biomedical health and the primary industries. In addition, the project will use state-of-the-art technology, including use of synchrotron radiation at the Monash-based Australian Synchrotron facility from 2007.Read moreRead less
ARC Centre for Structural & Functional Microbial Genomics. Australian Primary Industry will benefit from a team of experts in microbial genetics, bioinformatics and protein structure and function undertaking integrated studies on microbial genomics and phenomics that are focused on fundamental biological processes and host/pathogen interactions. Whole genome expression and protein profiling will be used to characterise genes whose expression is altered in the infected host and to analyse genes i ....ARC Centre for Structural & Functional Microbial Genomics. Australian Primary Industry will benefit from a team of experts in microbial genetics, bioinformatics and protein structure and function undertaking integrated studies on microbial genomics and phenomics that are focused on fundamental biological processes and host/pathogen interactions. Whole genome expression and protein profiling will be used to characterise genes whose expression is altered in the infected host and to analyse genes involved in the control of key cellular processes. The Centre will also determine the shapes of key molecules and their interactions. Practical outcomes will include new veterinary vaccines and the identification of novel antimicrobial targets.Read moreRead less