Discovery Early Career Researcher Award - Grant ID: DE130100251
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Biophysical mechanisms regulating early T cell signalling events. T cell activation in response to foreign pathogens or cancer cells requires a complex set of protein interactions which must be controlled in space and time. This project will use new microscopy methods with single-molecule sensitivity to determine how the cell membrane and protein clustering regulate these interactions.
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
Discovery Early Career Researcher Award - Grant ID: DE140101626
Funder
Australian Research Council
Funding Amount
$394,179.00
Summary
Flotillin link membrane microdomains to signalling endosome during T cell activation. This project aims to determine the mechanisms that connect signalling microdomains at the cell surface to intracellular signalling endosomes to regulate T cell activation. A T cell immune response begins with the reorganisation of the plasma membrane to yield two-dimensional signalling microdomains that must be connected to the three-dimensional microarchitecture of the endocytic matrix for full T cell activati ....Flotillin link membrane microdomains to signalling endosome during T cell activation. This project aims to determine the mechanisms that connect signalling microdomains at the cell surface to intracellular signalling endosomes to regulate T cell activation. A T cell immune response begins with the reorganisation of the plasma membrane to yield two-dimensional signalling microdomains that must be connected to the three-dimensional microarchitecture of the endocytic matrix for full T cell activation. This project hypothesises that Flotillin form distinct signalling microdomains in the plasma membrane that internalise to constitute an independent endocytic pathway. Using single-molecule and ultra-fast fluorescence imaging, the project will demonstrate that Flotillin represent a unique two-dimensional to three-dimensional regulatory mechanism for T cell signalling.Read moreRead less