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.
Developing orthogonal synthetic signaling cascades. This project proposes a generic approach for the construction of molecular switches based on artificially autoinhibited proteases. The bottom-up design of protein-based signaling networks is a key goal of synthetic biology. Yet, this remains elusive due to our inability to tailor-make signal transducers and receptors that can be readily compiled into defined signaling networks. Using structure-guided design and directed protein evolution, a set ....Developing orthogonal synthetic signaling cascades. This project proposes a generic approach for the construction of molecular switches based on artificially autoinhibited proteases. The bottom-up design of protein-based signaling networks is a key goal of synthetic biology. Yet, this remains elusive due to our inability to tailor-make signal transducers and receptors that can be readily compiled into defined signaling networks. Using structure-guided design and directed protein evolution, a set of protease-based signal transducers and ligand activated allosteric receptors will be created. The developed components are intended to be used to construct artificial signaling networks in mammalian cells that are orthogonal to the endogenous signaling cascades.Read moreRead less
Dynamic regulation of cell signalling scaffolds. This project aims to determine how cells utilise scaffold-type signalling proteins to orchestrate, over time, diverse cellular responses critical for normal development and physiology. The project expects to generate fundamental new knowledge in cell and synthetic biology with broad relevance that will foster establishment of new international linkages and networks. This research should benefit the biotechnology sector by identifying strategies fo ....Dynamic regulation of cell signalling scaffolds. This project aims to determine how cells utilise scaffold-type signalling proteins to orchestrate, over time, diverse cellular responses critical for normal development and physiology. The project expects to generate fundamental new knowledge in cell and synthetic biology with broad relevance that will foster establishment of new international linkages and networks. This research should benefit the biotechnology sector by identifying strategies for engineering scaffolds with desired biological outputs, with applications in areas such as large-scale cell production, immunotherapy, wound healing and regenerative medicine.Read moreRead less
The importance of exosomal membrane composition in intercellular signaling. Exosomes, microvesicles secreted by cells, are powerful signaling organelles. This project will explore the similarities and differences between the exosomal and host cell membrane. Membrane molecules exclusively present in exosomes may have important signaling implications and can aid in the uptake/fusion of exosomes by/with target cells.
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
Development and use of novel technologies to improve drugs targeting G protein-coupled receptor complexes involved in disease. The purpose of this project is to develop and use new and innovative technologies to improve many of the drugs taken for a wide range of medical conditions. The expected outcomes are the discovery of better drugs and a greater understanding of the drugs currently on the market, particularly enabling improved management of side-effects.
Activation of invasion in Toxoplasma. Host cell invasion is critical for the establishment and maintenance of infection by the single-celled parasite Toxoplasma gondii, the causative agent of Toxoplasmosis. This project will use the latest molecular techniques to understand how invasion is activated and will define a new set of drug targets to treat Toxoplasmosis and related diseases.
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