The Role And Underlying Mechanisms Of Constitutional Epigenetic Silencing In Cancer Predisposition
Funder
National Health and Medical Research Council
Funding Amount
$218,617.00
Summary
Familial and young onset bowel and uterine cancer are usually caused by the inheritance of spelling mistakes in the genetic code within a set of cancer-protection genes. Recently, some patients were identified with their gene switched off by paralysing chemicals instead. This study aims to identify additional cancer cases with gene paralysis, determine if this arises in the presence or absence of a genetic change in front of the gene, and how gene paralysis is transmitted to the next generation.
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
The Role And Inheritance Of Constitutional Epimutations In Early-onset Colorectal Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$347,551.00
Summary
Traditionally familial cancers are thought to be caused by spelling mistakes within the genetic code of cancer prevention genes. Our group has found that chemical attachments to one gene (MLH1) stops it working, even where there is no spelling mistake, and that those chemical changes can be inherited in families with bowel cancer. We will determine how frequently this type of defect occurs in bowel cancer patients, how and why it arises, and if other cancer genes are similarly affected.
Discovery of new genes for plant cellulose biosynthesis and improved fibre production. Cellulose, the world's most abundant biopolymer, is important to the cotton and forest industries and for human and animal nutrition. Before biotechnology can manipulate cellulose, we must identify the enzymes of the synthesis pathway and understand how their properties determine the properties of the cellulose they produce. Not all enzymes are known and any relationships to cellulose properties remain unexplo ....Discovery of new genes for plant cellulose biosynthesis and improved fibre production. Cellulose, the world's most abundant biopolymer, is important to the cotton and forest industries and for human and animal nutrition. Before biotechnology can manipulate cellulose, we must identify the enzymes of the synthesis pathway and understand how their properties determine the properties of the cellulose they produce. Not all enzymes are known and any relationships to cellulose properties remain unexplored. This study extends our successful mutational analysis of cellulose synthesis in Arabidopsis and initiates the molecular analysis of organisms making cellulose with distinctive properties. It will significantly advance knowledge of cellulose biosynthesis and identify novel genes for fibre improvement.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
Functional genomics of light stress resistance in the model organism Chlamydomonas: combining molecular genetics, transcriptome and proteome analysis. This project aims at combining molecular genetics, transcriptome and proteome analysis to identify genes and pathways underlying high light stress tolerance in previously isolated mutants of the chlorophyte Chlamydomonas reinhardtii. Comprehensive profiles of transcriptome-proteome linkage will be constructed without the complications of multicel ....Functional genomics of light stress resistance in the model organism Chlamydomonas: combining molecular genetics, transcriptome and proteome analysis. This project aims at combining molecular genetics, transcriptome and proteome analysis to identify genes and pathways underlying high light stress tolerance in previously isolated mutants of the chlorophyte Chlamydomonas reinhardtii. Comprehensive profiles of transcriptome-proteome linkage will be constructed without the complications of multicellularity for this unicellular photosynthetic model organism. We will establish a public proteome reference database and provide new microarrays and molecular markers beneficial for research in Chlamydomonas. We expect to advance understanding of high light resistance mechanisms so that it will eventually be applicable to improve productivity in crop plants growing under various environmental stress conditions.Read moreRead less
Flipping the mattress: infinite polyurethane recycling by synthetic biology. Australia is covered in billions of tonnes of plastic and yet <10% is recycled today. Polyurethane (PU) is ubiquitous in our everyday lives, from lacquer coatings to elastane clothing to durable foam padding in car seats, cushions and mattresses. Currently, there are few avenues for PU recycling and much ends up in landfill e.g., a single mattress produces 15-20kg of PU foam waste. Luckily, biodegradation of PU can occu ....Flipping the mattress: infinite polyurethane recycling by synthetic biology. Australia is covered in billions of tonnes of plastic and yet <10% is recycled today. Polyurethane (PU) is ubiquitous in our everyday lives, from lacquer coatings to elastane clothing to durable foam padding in car seats, cushions and mattresses. Currently, there are few avenues for PU recycling and much ends up in landfill e.g., a single mattress produces 15-20kg of PU foam waste. Luckily, biodegradation of PU can occur naturally via various microbial means and from insects, like Galleria mellonella larvae. The overall aim of this research project is to understand plastic biodegradation and translate nature’s solutions into flexible and efficient synthetic enzyme technologies that can sustainably recycle commonly used PU foams. Read moreRead less
Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. ....Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. Knowledge about this new aspect of protein degradation could provide a powerful tool to test the effect of the stabilisation or removal of specific proteins in the cell and also to develop new technologies in protein production.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