Detection Of Susceptibility Genes For Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$589,073.00
Summary
Multiple sclerosis is one of the most common chronic diseases of the nervous system. It usually starts in young adulthood and continues with episodes of severe disability from which partial recovery leads in many patients to difficulties with walking, balance, speech, bladder control and other neurologic functions. The disease inflicts a severe burden on both patients and the community. There is currently no preventive treatment and therapy is expensive (interferon at $20,000 p.a.) and of limite ....Multiple sclerosis is one of the most common chronic diseases of the nervous system. It usually starts in young adulthood and continues with episodes of severe disability from which partial recovery leads in many patients to difficulties with walking, balance, speech, bladder control and other neurologic functions. The disease inflicts a severe burden on both patients and the community. There is currently no preventive treatment and therapy is expensive (interferon at $20,000 p.a.) and of limited benefit in stopping further damage and of no benefit in reversing existing damage. New treatments will come through a full understanding of how the immune system attacks the brain to cause MS. There is a strong inherited component in MS and the discovery of the genes responsible should speed up the quest to understand the cause of the disease. The proposed studies involve international collaboration co-ordinated from Cambridge University, UK, in which the entire human genome will be screened looking for the MS genes using world s best available technology. Funding of this grant will allow Australia an equal seat at the table for this collaboration involving 17 countries. No individual country can recruit enough patients and hence this international effort is essential. It is expected that the understanding of the cause of MS will lead to new treatments that are effective and with low side effects.Read moreRead less
We propose an integrated program of bioinformatics research and capacity building focused on functional genomics. We will address research problems in the analysis and interpretation of high-volume genomic and proteomic data, in comparative sequence analysis, in determining the relation between genotype and phenotype using mutagenesis screens, and in making effective use of single nucleotide polymorphisms. Our capacity building will focus on the research training of students (undergraduates thro ....We propose an integrated program of bioinformatics research and capacity building focused on functional genomics. We will address research problems in the analysis and interpretation of high-volume genomic and proteomic data, in comparative sequence analysis, in determining the relation between genotype and phenotype using mutagenesis screens, and in making effective use of single nucleotide polymorphisms. Our capacity building will focus on the research training of students (undergraduates through the UROP scheme, honours and PhD) and postdoctoral scholars.Read moreRead less
Molecular Regulation Of Blood Cell Production And Function
Funder
National Health and Medical Research Council
Funding Amount
$18,333,174.00
Summary
The blood-forming system is an intricately controlled balance of cell proliferation, maturation and functional activity that is essential for oxygen transport throughout the body, blood clotting, and effective immune responses. Defining the genes and molecules that orchestrate blood cell production and function is crucial, not only for understanding the role of blood in health, but for establishing the bases of blood cell disorders such as autoimmunity and leukaemia, and for devising new clinica ....The blood-forming system is an intricately controlled balance of cell proliferation, maturation and functional activity that is essential for oxygen transport throughout the body, blood clotting, and effective immune responses. Defining the genes and molecules that orchestrate blood cell production and function is crucial, not only for understanding the role of blood in health, but for establishing the bases of blood cell disorders such as autoimmunity and leukaemia, and for devising new clinical strategies for fighting these lethal diseases. This program is conducted by a large, established team of investigators that have made world-class contributions to understanding blood cell formation and function for more than 30 years. Their work established the modern era of molecular haematology via discovery and analysis of blood cell hormones (colony-stimulating factors or CSFs), their receptors and intracellular mediators, which resulted in development of treatments for millions of cancer patients. The program is a multidisciplinary, team approach to fundamental biological questions with a focus on potential clinical and commercial outcomes involving collaborations with clinical medicine and the pharmaceutical industry. Research will focus on meshing novel genetic approaches in mice with translation studies in humans to identify new validated targets for therapeutic intervention in blood cell diseases, as well as building on the team s expertise in cytokine action with emphasis on the actions of the suppressor of cytokine signalling (SOCS) molecules, a key family of proteins that controls cytokine actions.Read moreRead less
Role of R-loops and double R-loops in genome organisation and transcription. The majority of our genome is converted to an extensive network of non-protein-coding RNA molecules (ncRNAs), but the function of these ncRNAs is unknown. This project aims to identify and determine the mechanism of action of nuclear ncRNA networks with a particular focus on nuclear ncRNAs that form RNA-DNA hybrids with the genomic DNA. These studies have the potential to lead to ground-breaking discoveries in our under ....Role of R-loops and double R-loops in genome organisation and transcription. The majority of our genome is converted to an extensive network of non-protein-coding RNA molecules (ncRNAs), but the function of these ncRNAs is unknown. This project aims to identify and determine the mechanism of action of nuclear ncRNA networks with a particular focus on nuclear ncRNAs that form RNA-DNA hybrids with the genomic DNA. These studies have the potential to lead to ground-breaking discoveries in our understanding of genome organisation and the mechanism of transcription control, and might provide an entirely new tool-box to manipulate genome function. This should provide significant benefits to efforts to develop innovative biotechnology and genome editing technologies in plants and animals.Read moreRead less
RNA surveillance and the initial steps of RNA biogenesis. This project aims to understand the initial steps of RNA biogenesis and how this process is linked to the chromatin environment. Although less than five per cent of our genome encodes proteins, almost the entire genome is transcribed to RNA. A large portion of these transcripts are degraded during the early steps of RNA biogenesis by the RNA surveillance machinery, but the mechanism for the recognition and degradation of these transcripts ....RNA surveillance and the initial steps of RNA biogenesis. This project aims to understand the initial steps of RNA biogenesis and how this process is linked to the chromatin environment. Although less than five per cent of our genome encodes proteins, almost the entire genome is transcribed to RNA. A large portion of these transcripts are degraded during the early steps of RNA biogenesis by the RNA surveillance machinery, but the mechanism for the recognition and degradation of these transcripts is not understood. New evidence suggests that the chromatin environment of the transcribed locus plays an important role in this process. This project will lead to significant benefits in the implementation of emerging RNA-based technologies and in understanding how genome stability is maintained.Read moreRead less
Statistical Methods For Identifying Structural Variation In Tumour Genomes Using Next Generation Sequencing
Funder
National Health and Medical Research Council
Funding Amount
$243,458.00
Summary
New DNA sequencing technology can sequence a tumour genome affordably in 2 weeks. This re-sequencing data can be used to find small mutations and large-scale chromosomal rearrangements that together are the drivers of cancer. These may one day be used to guide cancer therapy. This project will develop new algorithms for finding mutations and apply these to discover the genetic basis of drug resistance in a model lymphoma system.