Systems-level characterization of scaffold protein signalling networks. The PEAK family of cell signalling scaffolds regulate cellular responses critical for normal development and physiology. This project will adopt a ‘holistic’ approach to characterizing their mechanism and function, integrating experimental and mathematical approaches and developing predictive computational models. It aims to generate fundamental new knowledge in cell, computational and synthetic biology with broad relevance ....Systems-level characterization of scaffold protein signalling networks. The PEAK family of cell signalling scaffolds regulate cellular responses critical for normal development and physiology. This project will adopt a ‘holistic’ approach to characterizing their mechanism and function, integrating experimental and mathematical approaches and developing predictive computational models. It aims to generate fundamental new knowledge in cell, computational and synthetic biology with broad relevance that will foster establishment of new international linkages. This research will also identify strategies for engineering novel scaffolds that re-program cellular behaviour towards specific, applied outcomes, with potential benefit for the fields of synthetic biology, bioengineering and biotechnology.Read moreRead less
Defining the molecular switches that govern discrete cellular fates. This project aims to elucidate how mammalian cells exploit the same molecular machinery to perform completely distinct jobs. While the repurposing of proteins by cells seems widespread, the mechanisms by which this occurs remains largely undefined. The project expects to generate new knowledge in the areas of cell signalling and systems biology, with important implications for many multi-functional proteins. It will utilise a h ....Defining the molecular switches that govern discrete cellular fates. This project aims to elucidate how mammalian cells exploit the same molecular machinery to perform completely distinct jobs. While the repurposing of proteins by cells seems widespread, the mechanisms by which this occurs remains largely undefined. The project expects to generate new knowledge in the areas of cell signalling and systems biology, with important implications for many multi-functional proteins. It will utilise a highly innovative and interdisciplinary approach that tightly integrates mathematical modelling and biological experiments. The expected outcomes will aid strategies for reprogramming cells towards a desired phenotype, which will bring significant benefits to the fields of synthetic biology and bioengineering.Read moreRead less
Systems modelling of the cardiac fibroblast. The cardiac fibroblast is a specialised cell in the heart. New evidence shows that this cell type is central to heart function, but relatively little is known about how and why. This project will develop mathematical modelling to characterise how the cardiac fibroblast regulates the functioning of the adult heart.
Role of suppressor of cytokine signalling proteins (SOCS3) in defective muscle repair and ageing. Old muscles are slower and weaker than young muscles, they are injured more easily and they repair less successfully. This proposal investigates the role of SOCS3-signalling in muscle repair, ultimately to improve healing and to promote healthy ageing that will enable older Australians to enjoy a better quality of life.
The discovery and characterisation of novel protein regulators of blood cell formation. All of the mature blood cells in the human body are derived from a common ancestor cell type known as a stem cell. Our proposed studies will enhance our knowledge of how functional, mature blood cells are formed from stem cells and how dysregulation of these normally tightly controlled pathways can give rise to severe blood diseases.
Imaging the T cell signalling machinery . The conversion of external stimuli to the interior of a cell is a fundamental process that underpins many unique facets of biology, including cellular movement, nerve transmission, response to hormones and immune recognition. However, the basic mechanism by which such signals are transmitted across cellular membranes is poorly understood. This proposal will seek to bridge this gap in our knowledge by imaging a multi-component “decision-making” machine th ....Imaging the T cell signalling machinery . The conversion of external stimuli to the interior of a cell is a fundamental process that underpins many unique facets of biology, including cellular movement, nerve transmission, response to hormones and immune recognition. However, the basic mechanism by which such signals are transmitted across cellular membranes is poorly understood. This proposal will seek to bridge this gap in our knowledge by imaging a multi-component “decision-making” machine that controls whether or not the immune system becomes activated. Accordingly, this proposal will provide far-reaching insights into molecular events that are of central importance to the initiation of immunity, and thus will ultimately benefit society via improvements in health.Read moreRead less
Intramembrane Mechanics of Immunoreceptor Signalling. The cells of the immune system constantly survey the body for markers of injury and infection through molecular sensors that are responsive to the presence of pathogens, tumours and damaged cells. The goal of this project is to understand how the mechanical action of these molecular sensors direct the transmission of information to the cell interior.
Exceptions Prove the Rule: How Antigen Recognition Drives T cell Activation. CD8+ T cells are immune cells that are critical for the adaptive immune response, which is central to immune function in vertebrates. CD8+ T cells mediate their effector functions only after activation, which occurs via T cell receptor (TCR) recognition of foreign antigens. Here, unique reagents and sophisticated technologies will be used to define precisely how the nature of TCR-antigen recognition impacts on T cell ac ....Exceptions Prove the Rule: How Antigen Recognition Drives T cell Activation. CD8+ T cells are immune cells that are critical for the adaptive immune response, which is central to immune function in vertebrates. CD8+ T cells mediate their effector functions only after activation, which occurs via T cell receptor (TCR) recognition of foreign antigens. Here, unique reagents and sophisticated technologies will be used to define precisely how the nature of TCR-antigen recognition impacts on T cell activation and effector function. This work builds on an earlier identification of an entirely novel mode of TCR-antigen recognition, and its success will establish novel paradigms in T cell biology and represent a key advance in knowledge in the life sciences.Read moreRead less
Defining the molecular architecture of a lymphocyte-activating receptor complex. A robust immune response requires activation of sentinel T cells. This project will seek to understand the architecture of receptors at the T cell surface that allow these important immune cells to sense the presence of pathogens that react accordingly.
A molecular investigation into the naïve T cell repertoire. This project aims to interrogate the relationship between T cell receptor (TCR) recognition modes and T cell recruitment and activation. CD8+ T cells are important for adaptive immunity. Their recognition, via TCR, of peptides bound to MHC class I antigen-presenting molecules (pMHCI), initiates a signalling cascade which activates T cells effector functions. All structural information on TCR recognition of pMHCI is based on TCRs prevale ....A molecular investigation into the naïve T cell repertoire. This project aims to interrogate the relationship between T cell receptor (TCR) recognition modes and T cell recruitment and activation. CD8+ T cells are important for adaptive immunity. Their recognition, via TCR, of peptides bound to MHC class I antigen-presenting molecules (pMHCI), initiates a signalling cascade which activates T cells effector functions. All structural information on TCR recognition of pMHCI is based on TCRs prevalent in immune responses, and all recognise pMHCI using a conserved orientation. This project aims to use this observation to study the relationship between TCR recognition modes and T cell recruitment and activation.Read moreRead less