The Systems Biochemistry of Adaptation in Cellular Protein Networks. A living cell must process and interpret a host of diverse signals using a complex network of interacting proteins inside the cell. The detailed molecular mechanisms by which cells exhibit adaptation to these signals remains a fundamental question in biology. This project aims to develop a novel mathematical framework for analysing the capacity of intracellular protein interactions to contribute to cellular adaptation, along ....The Systems Biochemistry of Adaptation in Cellular Protein Networks. A living cell must process and interpret a host of diverse signals using a complex network of interacting proteins inside the cell. The detailed molecular mechanisms by which cells exhibit adaptation to these signals remains a fundamental question in biology. This project aims to develop a novel mathematical framework for analysing the capacity of intracellular protein interactions to contribute to cellular adaptation, along with a novel methodology for validating mathematical models against experimental data. These innovations offer a completely fresh approach to identifying and modulating the adaptive capacities of living cells, which may contribute to overcoming the problem of drug resistance in future therapeutic development.
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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
Engineering layered double hydroxide nanoparticles toward an efficient targeted clinical delivery system. This project will develop a more effective drug delivery system using clay nanoparticles and biofriendly serum proteins. Outcomes from this project will provide a tremendous opportunity for potent therapies of cancers, vasculature and neuronal diseases, and place Australia at the forefront of nanotechnology drug delivery research.
Molecular hallmarks of androgen receptor targeting in prostate cancer. There is a critical need in oncology drug development for better biomarkers of response to prostate cancer therapies, clinically to assist with treatment decision making, and pre-clinically to facilitate translation of emerging agents into clinical practice. Using a unique explant culture model, this project will identify protein and lipid markers that can be used to accurately and reliably assess response to androgen recepto ....Molecular hallmarks of androgen receptor targeting in prostate cancer. There is a critical need in oncology drug development for better biomarkers of response to prostate cancer therapies, clinically to assist with treatment decision making, and pre-clinically to facilitate translation of emerging agents into clinical practice. Using a unique explant culture model, this project will identify protein and lipid markers that can be used to accurately and reliably assess response to androgen receptor (AR)-targeting therapies in human prostate tumours. The identification and functional assessment of these biomarkers will identify those that can be used as surrogate endpoints in clinical trials, facilitate earlier approval of investigational agents and lead to improved options for therapeutic management of prostate cancer.Read moreRead less
Decoding miRNA regulated genetic circuits. This project will aim to develop a much better understanding of how the process of making proteins from genes is regulated, and will develop scientific software capable of predicting how a cell will respond to changes in this regulation. The results will have widespread use, including assistance in deciding the best treatments for genetic diseases.
A new Src, PKCdelta and Akt regulated protease activated receptor system in metastasis. In contrast with localised cancer which can often be cured, curative treatment is generally not possible for cancer that has spread. This project will characterise a protein that drives the spread of cancer and to develop new approaches to treat patients at risk of developing these aggressive tumours that spread to other organs.
Exploring novel coding genomic features through integrative proteogenomics. Knowledge of the full extent to which the human genome is made into proteins is of fundamental importance in the study of health and disease. New technological advances are now enabling functional studies of genomes with increasing detail. This project aims to develop and apply cutting edge bioinformatics methods to perform an integrative and comprehensive exploration of the extent to which the genes of a human cell line ....Exploring novel coding genomic features through integrative proteogenomics. Knowledge of the full extent to which the human genome is made into proteins is of fundamental importance in the study of health and disease. New technological advances are now enabling functional studies of genomes with increasing detail. This project aims to develop and apply cutting edge bioinformatics methods to perform an integrative and comprehensive exploration of the extent to which the genes of a human cell line are made into proteins. The project will improve our understanding of the human genome and deliver cutting edge methodology applicable for genome annotation in all living organisms.Read moreRead less
How do mechanical cues regulate tissue renewal and tumour progression? Imbalances between cell production and cell death in tissues can be catastrophic, leading to major global health issues such as cancer. This project will use modified mice and protein-protein interaction based techniques to identify how changes in the mechanical properties of tissues regulate the balance between cell production and cell death.
Development of disulphide-rich peptides for drug design. Peptides are an outstanding source of potential drug leads. This project seeks to build on earlier breakthroughs by developing stable, peptide-based drugs to combat cancer and autoimmune diseases. The peptides, derived from natural sources, are anticipated to provide drug leads that can ultimately lead to treatments for these diseases.
Inherited determinants of cancer aetiology. Family history of cancer is a strong risk factor for many cancers. This project will aim to identify inherited factors influencing risk of developing cancer and those factors influencing the course of the disease and outcomes.