Discovery Early Career Researcher Award - Grant ID: DE120102556
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
The influence of crosstalk between protein post-translational modifications on the propagation of molecular signals. The ability of a cell to respond appropriately to its surroundings is a result of interactions between proteins and chemical modifiers termed post-translational modifications (PTM). This project will show how PTM interactions (competition/ cooperation) influence cellular outcomes in response to changes in the environment.
Unravelling a canonical mitochondrial stress response pathway. Stress has a major impact on all life forms and is considered one of the key determinants of healthy ageing. This project aims to unravel a highly novel pathway through which many different forms of stress converge to induce a conserved stress response in mammalian cells. Major outcomes include rewriting the textbook on how stress is sensed by cells and how cells respond to this stress and will provide novel approaches and technologi ....Unravelling a canonical mitochondrial stress response pathway. Stress has a major impact on all life forms and is considered one of the key determinants of healthy ageing. This project aims to unravel a highly novel pathway through which many different forms of stress converge to induce a conserved stress response in mammalian cells. Major outcomes include rewriting the textbook on how stress is sensed by cells and how cells respond to this stress and will provide novel approaches and technologies for studying stress in a broad range of organisms and systems. This project will benefit all efforts to understand stress and aid efforts by others to ameliorate stress-mediated health defects across the animal kingdomRead moreRead less
Mechanisms of memory function involving site-specific tau phosphorylation. This project aims to understand the molecular principles that facilitate encoding, maintenance and retrieval of memories in the brain. To store memories in brain circuits, electrical and chemical signals are crucial. Brain cells can integrate signals into biochemical modifications of intracellular proteins. The nature of the protein modifications that represent memory within brain cells is unknown. This project uses innov ....Mechanisms of memory function involving site-specific tau phosphorylation. This project aims to understand the molecular principles that facilitate encoding, maintenance and retrieval of memories in the brain. To store memories in brain circuits, electrical and chemical signals are crucial. Brain cells can integrate signals into biochemical modifications of intracellular proteins. The nature of the protein modifications that represent memory within brain cells is unknown. This project uses innovative genome editing, mathematical modelling and proteomic approaches, to study how biochemical modifications of a key protein called tau help encode and retrieve memories. These molecular insights will make a significant advance in the current understanding of a brain function that is essential to all human activities.Read moreRead less
Novel regulatory mechanisms for the protein kinase Akt. This project aims to investigate unique feedback/feedforward regulatory behaviour of the protein kinase Akt by combining novel mathematical modelling with innovative lab methods for assessing Akt function in live cells. The project aspires to generate new knowledge that advances signal transduction research and provide computational and lab tools that provide an important resource for other researchers. The project will provide significant ....Novel regulatory mechanisms for the protein kinase Akt. This project aims to investigate unique feedback/feedforward regulatory behaviour of the protein kinase Akt by combining novel mathematical modelling with innovative lab methods for assessing Akt function in live cells. The project aspires to generate new knowledge that advances signal transduction research and provide computational and lab tools that provide an important resource for other researchers. The project will provide significant benefits such as transforming efforts to design Akt therapeutics and enabling other researchers to make new discoveries.Read moreRead less
Novel models to advance our understanding of mammalian development. This project aims to add to the understanding of cellular processes underpinning mammalian development. Protein phosphorylation is a dynamic process regulated by both protein kinases and protein phosphatases. While the role of kinases in cellular functions are well defined, the roles of protein phosphatases are not well understood. Using a range of laboratory models this project aims to discover the function of the phosphatase P ....Novel models to advance our understanding of mammalian development. This project aims to add to the understanding of cellular processes underpinning mammalian development. Protein phosphorylation is a dynamic process regulated by both protein kinases and protein phosphatases. While the role of kinases in cellular functions are well defined, the roles of protein phosphatases are not well understood. Using a range of laboratory models this project aims to discover the function of the phosphatase PP2A, in cell proliferation, survival, differentiation and DNA damage repair. The anticipated outcome is an improved understanding of all stages of mammalian development. This will provide significant benefits in the biotechnology, chemical and pharmaceutical industries.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160100282
Funder
Australian Research Council
Funding Amount
$377,500.00
Summary
Mechanotransduction within the Immune Synapse. This project plans to use advanced microscopy to study the forces involved in T-cell activation which lead to an immune response. T-cells readily detect the presence of even a single antigenic peptide-major histocompatibility complex (pMHC) and discriminate among thousands of endogenous pMHC via T-cell receptors (TCRs) on the surface of antigen-presenting cells. The mechanisms underlying this phenomenal sensitivity have remained elusive, but more re ....Mechanotransduction within the Immune Synapse. This project plans to use advanced microscopy to study the forces involved in T-cell activation which lead to an immune response. T-cells readily detect the presence of even a single antigenic peptide-major histocompatibility complex (pMHC) and discriminate among thousands of endogenous pMHC via T-cell receptors (TCRs) on the surface of antigen-presenting cells. The mechanisms underlying this phenomenal sensitivity have remained elusive, but more recent studies suggest mechanical forces to be instrumental. To investigate their role, the project plans to introduce force sensors into the immune synapse. Understanding the molecular mechanisms could provide new approaches to improving adoptive immunotherapy and to generating new hypotheses for drug development and targeting.Read moreRead less
Modulating T cell responses with novel Lck activating compounds. Modulating T cell responses with novel Lck activating compounds. This project aims to research T cell receptor (TCR) signal initiation and network plasticity and identify uses for drugs that affect the kinase Lck. The TCR signalling network has considerable plasticity so that modulation of one molecule (here the drug target is Lck) can have non-linear effects on T cell function. This project intends to use novel drugs to understand ....Modulating T cell responses with novel Lck activating compounds. Modulating T cell responses with novel Lck activating compounds. This project aims to research T cell receptor (TCR) signal initiation and network plasticity and identify uses for drugs that affect the kinase Lck. The TCR signalling network has considerable plasticity so that modulation of one molecule (here the drug target is Lck) can have non-linear effects on T cell function. This project intends to use novel drugs to understand how the T cell network can be exploited to control both the magnitude and quality of the T cell responses. This research is expected to aid the design of immune-modulating drugs.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100163
Funder
Australian Research Council
Funding Amount
$560,000.00
Summary
Single molecule imaging laboratory. Single molecule imaging laboratory: The goal of the project is to establish a single molecule imaging laboratory to close the gap between structural imaging and cellular imaging. Utilising the expertise of the ARC Centre of Excellence in Advanced Molecular Imaging, the aim of the project is to design, build and apply three microscopes that go beyond the current commercial solutions for single molecule localisation microscopy such as Photo-Activation Localisati ....Single molecule imaging laboratory. Single molecule imaging laboratory: The goal of the project is to establish a single molecule imaging laboratory to close the gap between structural imaging and cellular imaging. Utilising the expertise of the ARC Centre of Excellence in Advanced Molecular Imaging, the aim of the project is to design, build and apply three microscopes that go beyond the current commercial solutions for single molecule localisation microscopy such as Photo-Activation Localisation Microscopy (PALM) and Stochastic Optical Reconstruction Microscopy (STORM) and perform single molecule imaging: deep inside cells and tissue.The facility will have a fast acquisition rate to monitor highly dynamic molecular events, and improved precision to image molecules and complexes in intact cells with less than or equal to one nanometre resolution. There is currently no comparable imaging facility in the world.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE140100149
Funder
Australian Research Council
Funding Amount
$300,000.00
Summary
CyTOF platform for the Advanced Cytometry Facility: overcoming fluorescence spectral barriers to truly multiparametric cytometry by mass spectrometry. Cytometry by time-of-flight mass spectrometry platform for the Advanced Cytometry Facility: overcoming fluorescence spectral barriers to truly multiparametric cytometry by mass spectrometry: This project will provide a flow cytometer capable of analysing single cells by time-of-flight mass spectrometry. Antibody labels for cell components will ena ....CyTOF platform for the Advanced Cytometry Facility: overcoming fluorescence spectral barriers to truly multiparametric cytometry by mass spectrometry. Cytometry by time-of-flight mass spectrometry platform for the Advanced Cytometry Facility: overcoming fluorescence spectral barriers to truly multiparametric cytometry by mass spectrometry: This project will provide a flow cytometer capable of analysing single cells by time-of-flight mass spectrometry. Antibody labels for cell components will enable measurement of up to 100 parameters/cell. Developing analytical and modelling algorithms like Spanning tree Progression of Density normalised Events (SPADE), this project will aim to map the relationships of various unelucidated cell lineages, via functional pathway connections. New pathways thus revealed will enable elaboration and use of novel specific molecules in perturbational analyses to confirm and further enhance the understanding of these highly intricate, basic relationships. This will provide unparalleled insight, both into early development of stem cells and mechanisms of maintenance of homeostasis in differentiated cells.Read moreRead less
The combined use of proteomics and small molecules for target identification and pathway analysis. This project intends to investigate how a series of new small molecules identified from our research to improve the metabolic effects of insulin. This project will integrate medicinal chemistry with proteomics and metabolic biology to identify the cellular targets and their mechanism of action.