Alternative Splicing in the Mouse Transcriptome. Although the human genome completion is cause for excitement we do not have any firm indication of precisely how many protein-coding genes exist in a mammalian genome. We have even less indication of the extent to which these genes generate alternative gene products, through a process termed alternative splicing. The detection and sequencing of these full-length alternative gene products is the focus of this application. This application details t ....Alternative Splicing in the Mouse Transcriptome. Although the human genome completion is cause for excitement we do not have any firm indication of precisely how many protein-coding genes exist in a mammalian genome. We have even less indication of the extent to which these genes generate alternative gene products, through a process termed alternative splicing. The detection and sequencing of these full-length alternative gene products is the focus of this application. This application details the opportunity to participate in the identification of the full transcriptome of the mouse and is part of a collaborative effort with The RIKEN Genome Sciences Center in Japan.Read moreRead less
Statistical methods for detection of non-coding RNAs in eukaryote genomes. Understanding how eukaryotic cells work is a major goal of 21st century biology. A crucial step will be to catalogue the functional components of eukaryotic genomes. Australian researchers must be involved in this process at an early stage, in order to maximise commercial opportunities, attract quality researchers and position ourselves for further advances. This project will make major contributions to international effo ....Statistical methods for detection of non-coding RNAs in eukaryote genomes. Understanding how eukaryotic cells work is a major goal of 21st century biology. A crucial step will be to catalogue the functional components of eukaryotic genomes. Australian researchers must be involved in this process at an early stage, in order to maximise commercial opportunities, attract quality researchers and position ourselves for further advances. This project will make major contributions to international efforts in this area, via the development of statistical methods for segmenting genomes, classification of those segments, and study of the resulting classes. In the long term, enhanced understanding of eukaryotic cells will lead to breakthroughs in biology, and to medical, pharmaceutical, agricultural and scientific advances.Read moreRead less
Morphological development of the kidney – a paradigm for organogenesis. This project aims to shed new light on how the kidney develops, how normal adult function is established and how congenital kidney malformations occur. It aims to investigate a mathematical pattern that has been discovered in the program of branching morphogenesis which dictates kidney development. By combining cutting-edge genetic approaches, morphological analysis and mathematical modelling, this project plans to explore h ....Morphological development of the kidney – a paradigm for organogenesis. This project aims to shed new light on how the kidney develops, how normal adult function is established and how congenital kidney malformations occur. It aims to investigate a mathematical pattern that has been discovered in the program of branching morphogenesis which dictates kidney development. By combining cutting-edge genetic approaches, morphological analysis and mathematical modelling, this project plans to explore how this pattern is established, how it dictates kidney development and whether it constitutes an ancient mechanism central to organ formation. Project outcomes may improve understanding of fundamental developmental processes and developmental disease and variation. Project findings may also be important for understanding the development of other organ systems.Read moreRead less
The structure and patterning of branching morphogenesis in the developing kidney. This project aims to understand a fundamental developmental process known as branching morphogenesis, which drives the formation of many organs including the kidney, lungs and glands. Understanding this process will be of key importance in understand how our organs form.
A new hierarchy of mathematical models to quantify the role of ghrelin during cell invasion. Ghrelin is a recently-discovered growth factor that regulates appetite and promotes tumour growth by enhancing cell invasion. The mechanisms by which ghrelin enhances cell invasion are, at present, unknown. This innovative project will develop a new hierarchy of multiscale mathematical models that will be used to quantify how ghrelin modulates cell behaviour (motility, proliferation and death) and provid ....A new hierarchy of mathematical models to quantify the role of ghrelin during cell invasion. Ghrelin is a recently-discovered growth factor that regulates appetite and promotes tumour growth by enhancing cell invasion. The mechanisms by which ghrelin enhances cell invasion are, at present, unknown. This innovative project will develop a new hierarchy of multiscale mathematical models that will be used to quantify how ghrelin modulates cell behaviour (motility, proliferation and death) and provide insight into the precise details of how ghrelin promotes cell invasion. This project will demonstrate the potential for ghrelin-based strategies to control cell invasion. By linking appetite regulation and tumour growth, the outcomes from this project will inform Australian health policy in this important area.Read moreRead less
Mutagenesis and combinatorial algorithms for sequencing problematic genomic regions. This project will develop a remarkable and original approach to DNA sequencing with potential to radically improve the speed, accuracy and effectiveness of existing sequencing technologies. It is especially useful for dealing with difficult-to-sequence genomic regions and has implications for all sequencing projects, including completion of the Human Genome Project. The approach involves generating, and wholly o ....Mutagenesis and combinatorial algorithms for sequencing problematic genomic regions. This project will develop a remarkable and original approach to DNA sequencing with potential to radically improve the speed, accuracy and effectiveness of existing sequencing technologies. It is especially useful for dealing with difficult-to-sequence genomic regions and has implications for all sequencing projects, including completion of the Human Genome Project. The approach involves generating, and wholly or partially sequencing, mutated copies of problematic regions of the target genome. Advanced combinatorial algorithms are then used to form highly probable alignments between strings and determine the unknown sequence. The approach has additional benefits in detecting single-nucleotide polymorphisms and sequencing errors.Read moreRead less
Statistical Methods for Discovering Ribonucleic acids (RNAs) contributing to human diseases and phenotypes. Identifying the causative genetic factors involved in quantitative phenotypes and diseases is a major goal of biology in the 21st century and beyond. A crucial step towards this goal is identifying and classifying the functional non-protein-coding Ribonucleic acids (RNAs) encoded in the human genome. This project will make major contributions to international efforts in this area by identi ....Statistical Methods for Discovering Ribonucleic acids (RNAs) contributing to human diseases and phenotypes. Identifying the causative genetic factors involved in quantitative phenotypes and diseases is a major goal of biology in the 21st century and beyond. A crucial step towards this goal is identifying and classifying the functional non-protein-coding Ribonucleic acids (RNAs) encoded in the human genome. This project will make major contributions to international efforts in this area by identifying RNA molecules that contribute to quantitative phenotypes including susceptibility to disease. As such, it will directly benefit fundamental science via the discovery and classification of new molecules. Indirectly, it will lead to breakthroughs in biology, and consequently to major medical and pharmaceutical advances in the diagnosis and treatment of genetic disease.Read moreRead less
New data-driven mathematical models of collective cell motion. Cancer and chronic wounds are a national, and indeed, international health problem set to worsen as our population ages. Predictive and interpretive tools are required to improve our understanding of collective cell migration in relation to cancer and chronic wounds. This project will produce new validated mathematical tools for predicting collective cell migration in a general framework that can deal with application-specific detail ....New data-driven mathematical models of collective cell motion. Cancer and chronic wounds are a national, and indeed, international health problem set to worsen as our population ages. Predictive and interpretive tools are required to improve our understanding of collective cell migration in relation to cancer and chronic wounds. This project will produce new validated mathematical tools for predicting collective cell migration in a general framework that can deal with application-specific details, such as the role of cell shape and cell size. Although cell shape and size are known to affect collective cell migration, standard mathematical models ignore these details. This project will produce new predictive mathematical modelling tools that are validated by new experimental data. Read moreRead less
Modelling cell invasion incorporating the epithelial to mesenchymal transition: Exploring therapies to control wound healing and cancer progression. Cancer and wounds are closely related, commonly lethal, diseases. Both require cell growth and invasion. This project will apply experimental measurements to create new mathematical models of cancer and wounds; models that will inform new targets and strategies for the treatment of these deadly diseases.
Development and validation of virtual epithelial cancer models using an integrated modelling and experimental three-dimensional approach. The mathematical and experimental modelling of the human prostate and ovary applying quantitative bioengineering concepts will lead to virtual cancer models. This project aims to validate these multi-scale models to delineate biological and pathological avenues in healthy and disease tissue and improve prevention and treatment of prostate and ovarian cancer.