Discovery Early Career Researcher Award - Grant ID: DE240101055
Funder
Australian Research Council
Funding Amount
$448,737.00
Summary
How blood vessel stiffness regulates their growth and maintenance. This project aims to reveal an unidentified molecular mechanism of how endothelial cells in the walls of blood vessels detect stiffness of the surrounding environment in order to regulate blood vessel growth and maintenance. The results are expected to advance the emerging field of mechanobiology by combining cutting-edge cell biology and microscopy techniques carried out in novel 3D cell culture and unique quail models. The bene ....How blood vessel stiffness regulates their growth and maintenance. This project aims to reveal an unidentified molecular mechanism of how endothelial cells in the walls of blood vessels detect stiffness of the surrounding environment in order to regulate blood vessel growth and maintenance. The results are expected to advance the emerging field of mechanobiology by combining cutting-edge cell biology and microscopy techniques carried out in novel 3D cell culture and unique quail models. The benefits of these outcomes include generation of knowledge on the impact of tissue stiffness on the signalling mechanisms that drive formation and maintenance of blood vessels. In the long term, this fundamental understanding could give rise to major developments in emerging industries such as organ bioengineering.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101128
Funder
Australian Research Council
Funding Amount
$444,154.00
Summary
Decode Neuro-Mechanobiology:mechanosensitive ion channels in proprioception. Human bodies are densely covered with numerous mechanosensory neurons that provide us with the sense of touch and pain. However, the molecular force sensors remain poorly identified. This project aims at defining the fundamental roles of mechanosensitive ion channels to sense and respond to various mechanical stimuli, and how their responses may encode mechanical cues.The ultimate goal is to provide a fundamentally new ....Decode Neuro-Mechanobiology:mechanosensitive ion channels in proprioception. Human bodies are densely covered with numerous mechanosensory neurons that provide us with the sense of touch and pain. However, the molecular force sensors remain poorly identified. This project aims at defining the fundamental roles of mechanosensitive ion channels to sense and respond to various mechanical stimuli, and how their responses may encode mechanical cues.The ultimate goal is to provide a fundamentally new understanding of proprioception and motion sensing. The new multimodality approach generated in this project is expected to evolve as a national facility for neuro-mechanobiology, and future research may lead to the inspiration of novel bionic sensor design and brain-computer interface for future neuroengineering industry.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190100609
Funder
Australian Research Council
Funding Amount
$368,000.00
Summary
Mechanobiology: a new model of integrin activation by membrane tension. This project aims to address a fundamental question in mechanobiology on how integrin receptor coordinates with force to mediate cell spreading, migration, growth and survival. With an observation that membrane deformation enhances integrin binding, the project expects to establish a new model of integrin activation by membrane tension. It will develop an integrated approach combining single-molecule force probes, super reso ....Mechanobiology: a new model of integrin activation by membrane tension. This project aims to address a fundamental question in mechanobiology on how integrin receptor coordinates with force to mediate cell spreading, migration, growth and survival. With an observation that membrane deformation enhances integrin binding, the project expects to establish a new model of integrin activation by membrane tension. It will develop an integrated approach combining single-molecule force probes, super resolution microscopy, microfluidics and molecular dynamics simulations. It is expected that the role of membrane tension in promoting cell adhesion will be defined at molecular scale, and the link between integrin activation and Piezo calcium channel mediated membrane tension sensing will be delineated.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101536
Funder
Australian Research Council
Funding Amount
$473,824.00
Summary
How does heme regulate blood vessel formation in the brain? There are more than 600 kilometres of blood vessels in the brain, all of which are lined by tightly packed cells that protect the brain from toxins. My research aims to investigate how these blood vessels are formed. This project expects to reveal the role that a critical signalling molecule called heme plays in this fundamental biological process. I will use cutting-edge structural biology and biophysical techniques to uncover the mole ....How does heme regulate blood vessel formation in the brain? There are more than 600 kilometres of blood vessels in the brain, all of which are lined by tightly packed cells that protect the brain from toxins. My research aims to investigate how these blood vessels are formed. This project expects to reveal the role that a critical signalling molecule called heme plays in this fundamental biological process. I will use cutting-edge structural biology and biophysical techniques to uncover the molecular mechanisms that allow heme to enter cells and regulate blood vessel growth in the brain. The outcomes of this research will enhance our understanding of the brain’s core infrastructure and will contribute to an understanding of how cerebral blood vessels grow and maintain integrity. Read moreRead less
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: DE120102914
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Membrane protein function in its native lipid environment characterised by solid-state nuclear magnetic resonance. Membrane proteins play an important role for cell function and have vast medical implications, whereas their function is crucially dependent on mechanisms related to their embedding in the membrane. These features will be characterised by newly developed spectroscopic methods, which will further contribute to an improved understanding of 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
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
Discovery Early Career Researcher Award - Grant ID: DE140101788
Funder
Australian Research Council
Funding Amount
$358,920.00
Summary
Structural Analysis of Biomolecular Complexes at Membrane Interfaces Important to Health and Disease. This project will study structural aspects of key biomolecular complexes at membrane interfaces that are involved with apoptosis (programmed cell death). Malfunctions in apoptosis have been implicated in many aliments including age-related diseases and cancers. Understanding of the molecular and structural aspects of key complexes can pave the way to novel therapies. The approach that will be us ....Structural Analysis of Biomolecular Complexes at Membrane Interfaces Important to Health and Disease. This project will study structural aspects of key biomolecular complexes at membrane interfaces that are involved with apoptosis (programmed cell death). Malfunctions in apoptosis have been implicated in many aliments including age-related diseases and cancers. Understanding of the molecular and structural aspects of key complexes can pave the way to novel therapies. The approach that will be used is to design new biomimetic outer mitochondrial membranes and use these to study the structure and binding of proteins involved with apoptosis. By studying simple models of complex systems, this project promises to yield detailed information on important biomolecular complexes where structural detail is currently lacking. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220101424
Funder
Australian Research Council
Funding Amount
$434,282.00
Summary
Molecular basis of Prestin’s electromotility and sound discrimination . Sonar animals like whales can hear at exceptionally high frequencies allowing them to echolocate. Humans, though, can hear at much higher frequencies than reptiles and birds. Frequency sensing mainly depends on a protein in the ear called Prestin. Currently, the structure and working mechanism of Prestin is unknown. This project aims to characterize how Prestin responds to high frequencies by probing the electro-mechanical f ....Molecular basis of Prestin’s electromotility and sound discrimination . Sonar animals like whales can hear at exceptionally high frequencies allowing them to echolocate. Humans, though, can hear at much higher frequencies than reptiles and birds. Frequency sensing mainly depends on a protein in the ear called Prestin. Currently, the structure and working mechanism of Prestin is unknown. This project aims to characterize how Prestin responds to high frequencies by probing the electro-mechanical force generated using mechanically gated channels as a reporter. Single particle cryo-electron microscopy will also be used to visualize Prestin’s 3D structure. Together, this DECRA project will elucidate the molecular basis of hearing differences across species and reshapes our understanding of the evolution of hearing.Read moreRead less