Transcriptional and epigenetic regulation of terminal lymphocyte differentiation and alterations of the same that lead to leukemia. In the developed world infection diseases are the number three killer behind heart disease and cancer, and huge financial effort is put into treatment and prevention. Despite this, results have often been disappointing. One cause of these poor outcomes is the lack of knowledge of how effective immune responses are generated. This project aims to better understand th ....Transcriptional and epigenetic regulation of terminal lymphocyte differentiation and alterations of the same that lead to leukemia. In the developed world infection diseases are the number three killer behind heart disease and cancer, and huge financial effort is put into treatment and prevention. Despite this, results have often been disappointing. One cause of these poor outcomes is the lack of knowledge of how effective immune responses are generated. This project aims to better understand the processes that control the generation of protective lymphocytes. It will deliver information that may enable a more targeted approach to vaccine-development and treatments of infections. As defective differentiation can also be a cause of leukemia it may also lead to targets of cancer treatment.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775778
Funder
Australian Research Council
Funding Amount
$196,000.00
Summary
A microarray platform for gene expression analysis and genotyping in biological systems. This technology has substantial benefits for basic science and biotechnology. The ability to rapidly study changes in gene expression in living organisms will benefit agriculture, animal and biomedical science and biotechnology. The Affymetrix platform creates opportunities for new avenues of research, such as studying epigenetic (DNA and protein modifications) mechanisms in development, ageing and disease. ....A microarray platform for gene expression analysis and genotyping in biological systems. This technology has substantial benefits for basic science and biotechnology. The ability to rapidly study changes in gene expression in living organisms will benefit agriculture, animal and biomedical science and biotechnology. The Affymetrix platform creates opportunities for new avenues of research, such as studying epigenetic (DNA and protein modifications) mechanisms in development, ageing and disease. The project falls within the designated national research priority areas of 'promoting and maintaining good health" and the priority goals of "a healthy start to life", "aging well", "aging productively" and "preventative health care."Read moreRead less
Discovering genes and mechanisms regulating immune responses. The Fellowship will retain and expand a pioneering Australian research program, and attract to Australia major international investment and technology linkages, making use of the DNA sequence of humans and other mammals to advance understanding of immunity and infection control in public health, agriculture and industry. The program will build on Australia's pre-eminent research strengths in the field of immunity and infection, and w ....Discovering genes and mechanisms regulating immune responses. The Fellowship will retain and expand a pioneering Australian research program, and attract to Australia major international investment and technology linkages, making use of the DNA sequence of humans and other mammals to advance understanding of immunity and infection control in public health, agriculture and industry. The program will build on Australia's pre-eminent research strengths in the field of immunity and infection, and will create new knowledge and resources to improve human and animal health through vaccines, pharmaceuticals and public health policy. Read moreRead less
Monotreme immune system provides insights into their evolutionary relationships. Genes of immunological importance will be cloned and characterised from the short-beaked echidna with the purpose of investigating the immune system in monotremes, gaining insights into the timing and order of evolutionary separation of the three extant mammalian groups:- the Prototherians (monotremes), the Metatherians (marsupials) and Eutherians (placentals), increasing understanding of the evolution of the verteb ....Monotreme immune system provides insights into their evolutionary relationships. Genes of immunological importance will be cloned and characterised from the short-beaked echidna with the purpose of investigating the immune system in monotremes, gaining insights into the timing and order of evolutionary separation of the three extant mammalian groups:- the Prototherians (monotremes), the Metatherians (marsupials) and Eutherians (placentals), increasing understanding of the evolution of the vertebrate immune system and providing the basis for making immunological reagents which are necessary for studying monotreme diseases (as a precautionary conservation strategy).Read moreRead less
From the pouch to the grave: age and sex related changes in immunity in the Tasmanian devil. Tasmanian devils face extinction in the wild due to the emergence of a contagious cancer: Devil Facial Tumour Disease (DFTD). A comprehensive understanding of the devil immune system is necessary to better understand the disease and develop a vaccine against it. This project will characterise immune responses of healthy devils throughout life, from the pouch, to onset of puberty, to old age. This project ....From the pouch to the grave: age and sex related changes in immunity in the Tasmanian devil. Tasmanian devils face extinction in the wild due to the emergence of a contagious cancer: Devil Facial Tumour Disease (DFTD). A comprehensive understanding of the devil immune system is necessary to better understand the disease and develop a vaccine against it. This project will characterise immune responses of healthy devils throughout life, from the pouch, to onset of puberty, to old age. This project will then compare these responses in DFTD-affected devils to determine why DFTD affects older animals first and does not affect sexually-immature devils. Additional outcomes will include the development of novel antibiotics against human and animal diseases and an atlas of devil development using the latest imaging technologies.Read moreRead less
Noncoding RNAs As Prognostic Markers And Therapeutic Targets In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$550,283.00
Summary
Normal human development involves a symphony of genetic changes that control the growth and differentiation of different types of cells during embryogenesis. For many years it has been assumed that most genetic information is transacted by proteins, and that the remaining 98% of the human genome that does not encode proteins was (apart from a limited amount of associated regulatory elements) largely non-functional evolutionary junk. However, this may not be the case. Recent results from our labo ....Normal human development involves a symphony of genetic changes that control the growth and differentiation of different types of cells during embryogenesis. For many years it has been assumed that most genetic information is transacted by proteins, and that the remaining 98% of the human genome that does not encode proteins was (apart from a limited amount of associated regulatory elements) largely non-functional evolutionary junk. However, this may not be the case. Recent results from our laboratory and others have shown that most of our genome and that of other mammals is actually expressed as noncoding RNA, which appears to be developmentally regulated. These RNAs (of which there appear to be tens of thousands, well outnumbering the protein-coding mRNAs) have been referred to as the hidden layer or dark matter of our genome, as they have barely been studied, but appear to play a central role in both normal and abnormal development in humans. There is now increasing evidence that many noncoding RNAs, including small regulatory RNAs called microRNAs, are perturbed in cancer and that these perturbations may be directly involved in, and be an accurate indicator of, cancer state and the direction of cancer progression. If this is true we need to understand the expression and functions of these RNAs in order to develop better diagnostics and perhaps powerful new therapeutics for cancer, based on RNA technology and generic delivery systems. This project will explore the patterns of noncoding RNA expression in normal breast development and in breast cancer, to identify those RNAs that direct or accompany the differentiation of these tissues, and to test the effects of interfering with their expression on these processes. These foundation studies lie at the leading edge of a new understanding of human genetics and cancer, and will provide a platform for future applications in medicine that utilize this information and understanding.Read moreRead less
The mucosal immune system of fish: analysis of the immune repertoire in gut-and gill-associated lymphoid tissues in trout. Infectious disease causes major economic loss to the aquaculture industry, highlighting the need for effective vaccination strategies. While oral or immersion vaccination represents the most cost effective means of protecting fish against infectious disease there are problems associated with inducing an effective immune response in fish that will assist our industry partner ....The mucosal immune system of fish: analysis of the immune repertoire in gut-and gill-associated lymphoid tissues in trout. Infectious disease causes major economic loss to the aquaculture industry, highlighting the need for effective vaccination strategies. While oral or immersion vaccination represents the most cost effective means of protecting fish against infectious disease there are problems associated with inducing an effective immune response in fish that will assist our industry partner (Novartis Animal Vaccines Ltd) to develop improved fish vaccines. The project will provide postgraduate training in the area of fish immunology that is vital to the developing Australian aquaculture industry.Read 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.
Detection Of Alternative Lengthening Of Telomeres In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$471,000.00
Summary
In each cell, DNA is packaged into units called chromosomes, the ends of which (i.e., telomeres) become slightly shorter every time they are replicated during the production of new cells. Continued cell replication and hence continued telomere shortening eventually results in the inability of cells to replicate themselves any further. Normal cells have mechanisms to slow down, but not completely prevent telomere shortening. The development of a cancer depends on its cells being able to replicate ....In each cell, DNA is packaged into units called chromosomes, the ends of which (i.e., telomeres) become slightly shorter every time they are replicated during the production of new cells. Continued cell replication and hence continued telomere shortening eventually results in the inability of cells to replicate themselves any further. Normal cells have mechanisms to slow down, but not completely prevent telomere shortening. The development of a cancer depends on its cells being able to replicate themselves many times, and therefore they need to find a method to prevent their telomeres shortening. We discovered one such method, called Alternative Lengthening of Telomeres (ALT), that is used by some cancers. It has been shown in principle that cancer cells can be killed by disrupting their ability to prevent telomere shortening. Therefore, in another project we are developing methods needed to find drugs that inhibit ALT. In the meantime, we have found the first evidence that some normal cells have an ALT-like mechanism. Our speculation is that cancer cells are able to dysregulate and subvert this normal mechanism in order to prevent their telomeres from shortening. In this project, we will analyse the ALT-like mechanism in mice, to determine its characteristics, and to determine what tissues use it. This information will provide critically important insights into the ALT mechanism itself, and the likely side effects of drugs that inhibit ALT.Read moreRead less