Mathematical Methods for Next Generation Sequencing. The emergence of a new generation of high throughput genomic sequencing technologies is providing unprecedented opportunities for biological research. Hidden within the huge amounts of data generated by this technology is information about the expression and regulation of genes, and the complex functional purpose of non-coding, so called 'junk', DNA. Development of mathematical and statistical tools is essential to interpreting these data. The ....Mathematical Methods for Next Generation Sequencing. The emergence of a new generation of high throughput genomic sequencing technologies is providing unprecedented opportunities for biological research. Hidden within the huge amounts of data generated by this technology is information about the expression and regulation of genes, and the complex functional purpose of non-coding, so called 'junk', DNA. Development of mathematical and statistical tools is essential to interpreting these data. The proposed research will enhance Australia's reputation for developing novel quantitative techniques at the cutting edge of modern biology. The proposed project has a broad range of potential applications in biotechnology, particularly in the medical and agricultural industries.Read moreRead less
Advanced fluid mechanics modelling of complex leukocyte-endothelial interactions. This project adopts an interdisciplinary approach toward understanding the mechanical interactions between blood cells and vessel walls, under different hydrodynamic conditions. Outcomes will have downstream benefits to vascular biology in relation to diagnosis of problems such as atherosclerotic plaques. These vascular problems are associated with several major health problems including coronary heart disease, h ....Advanced fluid mechanics modelling of complex leukocyte-endothelial interactions. This project adopts an interdisciplinary approach toward understanding the mechanical interactions between blood cells and vessel walls, under different hydrodynamic conditions. Outcomes will have downstream benefits to vascular biology in relation to diagnosis of problems such as atherosclerotic plaques. These vascular problems are associated with several major health problems including coronary heart disease, hypertension, stroke, diabetes and kidney dysfunction.Read moreRead less
Neurotrophic factors for pelvic autonomic neurons: the role of neurturin. This project is about pelvic parasympathetic neurons, which are responsible for involuntary activities such as bladder voiding and penile erection. We are interested in the neurotrophic factors that determine survival of these neurons during early mammalian development and keep them healthy in adults. Little is known about ?parasympathetic neurotrophic factors? in general. However we have recently discovered that the prote ....Neurotrophic factors for pelvic autonomic neurons: the role of neurturin. This project is about pelvic parasympathetic neurons, which are responsible for involuntary activities such as bladder voiding and penile erection. We are interested in the neurotrophic factors that determine survival of these neurons during early mammalian development and keep them healthy in adults. Little is known about ?parasympathetic neurotrophic factors? in general. However we have recently discovered that the protein neurturin is very important in the pelvic parasympathetic system. We will determine exactly how neurturin affects pelvic neurons and how it interacts with other neurotrophic factors. Our results will fill a major gap in our knowledge of fundamental neurobiology.Read moreRead less
Genetics and evolution of Shigella O antigens. We use genome scale sequencing techniques to sequence 26 O-antigen gene clusters from Shigella. With the seven already known, this will give sequences for every O-antigen of Shigella. This will be the first time that such set is fully sequenced. Shigella are human specific pathogens, have emerged with the evolution of humans. O-antigens are important for their life and pathogenicity. This project will greatly extend our knowledge of the genetic basi ....Genetics and evolution of Shigella O antigens. We use genome scale sequencing techniques to sequence 26 O-antigen gene clusters from Shigella. With the seven already known, this will give sequences for every O-antigen of Shigella. This will be the first time that such set is fully sequenced. Shigella are human specific pathogens, have emerged with the evolution of humans. O-antigens are important for their life and pathogenicity. This project will greatly extend our knowledge of the genetic basis and evolution of this important polymorphism. O-antigens are used for typing Shigella and also elicit strong immunity. The molecular data will help establish DNA based typing and vaccine development.Read moreRead less
Phyloinformatics and biodiversity: developing bioinformatic tools for understanding the dynamics of extinction and invasion within species assemblages. DNA sequence data provides an exciting new way to study biodiversity, because the genome of each organism records its evolutionary history. By analysing DNA sequences co-existing species, we can reconstruct the ecological and evolutionary history of a biological community. This allows us to track biodiversity changes over time, and examine how th ....Phyloinformatics and biodiversity: developing bioinformatic tools for understanding the dynamics of extinction and invasion within species assemblages. DNA sequence data provides an exciting new way to study biodiversity, because the genome of each organism records its evolutionary history. By analysing DNA sequences co-existing species, we can reconstruct the ecological and evolutionary history of a biological community. This allows us to track biodiversity changes over time, and examine how the state of a species assemblage determines which species are lost through extinction or gained through the invasion of exotic species. Understanding the factors that govern changes in biodiversity over time is essential for planning for future conservation in the face of a rapidly changing environment. Read moreRead less
Testing the free radical theory of aging: do indicators of oxidative damage predict lifespan? Because of the Free Radical Theory of Aging, many millions of dollars are spent around the world on dietary antioxidants of unproven efficacy. Many millions of research dollars are spent providing support for this theory but few studies test it rigorously. The first major benefit of this research is worldwide; to refute, or to substantially enhance and focus the current support for the Free Radical Theo ....Testing the free radical theory of aging: do indicators of oxidative damage predict lifespan? Because of the Free Radical Theory of Aging, many millions of dollars are spent around the world on dietary antioxidants of unproven efficacy. Many millions of research dollars are spent providing support for this theory but few studies test it rigorously. The first major benefit of this research is worldwide; to refute, or to substantially enhance and focus the current support for the Free Radical Theory. This should help to rationalise and direct funding supplied to these areas. The second benefit is for Australia: aging is a fruitful area for research because of the high general public interest and for training because of its multidisciplinary nature, and funding in Australia is very low by international standards. Read moreRead less
Combined genetic and cellular analysis of melanisation to study variation in human pigmentation. This investigation examines variations in the genes that are important determinants of human skin pigmentation and are likely to be associated with skin cancer risk. Our research program will form the basis of future diagnostics based on major genes that determine a persons skin type. Current skin cancer prevention strategies rely predominantly on broad spectrum campaigns that are aimed at increasi ....Combined genetic and cellular analysis of melanisation to study variation in human pigmentation. This investigation examines variations in the genes that are important determinants of human skin pigmentation and are likely to be associated with skin cancer risk. Our research program will form the basis of future diagnostics based on major genes that determine a persons skin type. Current skin cancer prevention strategies rely predominantly on broad spectrum campaigns that are aimed at increasing the general community awareness of the damaging effects of UV radiation. A better understanding of the genetic basis of UV-sensitive skin types will greatly enhance the targeting of such skin cancer-prevention campaigns, provide an understanding of changes that occur in skin pathology, and the mechanisms of sun induced tanning.Read moreRead less
Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in bi ....Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in biotechnology. The ultimate aim is to create novel technologies for protein production, modification and analysis that will accelerate the pace of discovery in protein research, basic cell and organism biology, diagnostics, biotechnology and drug discovery. Read moreRead less
Sperm competition, sexual conflict, and gamete evolution in mice. The innovative experiments of this project will yield results that are at the forefront of research in evolutionary biology. This project will generate publications in high profile journals, and will foster collaborations between Australian and European researchers, creating a significant international impact and promoting excellence in Australian research. Since European settlement of Australia, sixty percent of the native rodent ....Sperm competition, sexual conflict, and gamete evolution in mice. The innovative experiments of this project will yield results that are at the forefront of research in evolutionary biology. This project will generate publications in high profile journals, and will foster collaborations between Australian and European researchers, creating a significant international impact and promoting excellence in Australian research. Since European settlement of Australia, sixty percent of the native rodent species have become extinct or are threatened with extinction. As there is a significant lack of research on the mating systems of Australian rodents, our investigations on a native mouse will generate information that will be extremely valuable to the national conservation efforts of threatened rodent species.Read moreRead less
Identifying genes causing thermal evolution of ectotherm body size. Cold-blooded animals increase in body size as they are found in populations at greater distances from the equator. These patterns are due to populations adapting to temperature. The aim of this project is to identify the genes involved in this adaptation process. We will do this by taking advantage of a well-studied body size cline in the vinegar fly on the east coast of Australia, and by building on an international collaborati ....Identifying genes causing thermal evolution of ectotherm body size. Cold-blooded animals increase in body size as they are found in populations at greater distances from the equator. These patterns are due to populations adapting to temperature. The aim of this project is to identify the genes involved in this adaptation process. We will do this by taking advantage of a well-studied body size cline in the vinegar fly on the east coast of Australia, and by building on an international collaboration between a leading UK and two Australian research groups. In doing so we will provide an explanation at the molecular level for one of the great unresolved phenomena in biology: why do cold-blooded animals get bigger in the cold? The research also leads to the potential to manipulate body size in animals.Read moreRead less