Computational enzymology: exploring the free energy landscape of enzymatic catalysis. Most biochemical reactions depend on enzyme catalysis and understanding how enzymes work at the molecular level remains a central question. This project will develop a suite of computational models to study the mechanisms of enzyme-catalysed reactions and such knowledge holds promise for technological benefits in the form of new drugs and novel catalysts.
Protein structure controls light harvesting in photosynthetic light algae. The strange phenomena of quantum mechanics were not expected to play a direct role in life, however, it appears that quantum effects may be important in the efficient capture of sunlight for photosynthesis. The conditions for the emergence of quantum phenomena appear to be set by the structures of proteins. The aim of this project is to relate protein structure to the emergence of quantum effects in the light harvesting p ....Protein structure controls light harvesting in photosynthetic light algae. The strange phenomena of quantum mechanics were not expected to play a direct role in life, however, it appears that quantum effects may be important in the efficient capture of sunlight for photosynthesis. The conditions for the emergence of quantum phenomena appear to be set by the structures of proteins. The aim of this project is to relate protein structure to the emergence of quantum effects in the light harvesting proteins of marine algae. Understanding the link between structure and quantum effects could improve our knowledge of how nature achieves its remarkable efficiency in utilising the energy from the sun. This is likely to foster new technologies that improve the efficiency of solar energy systems.Read moreRead less
Flick the biological quantum switch: light controls photosynthetic proteins. This project aims to determine whether light conditions dictate which proteins, and hence quantum properties, a marine alga selects. The protein structures determine whether non-trivial quantum effects are available to the alga. Expected outcomes include fostering new technologies which will provide significant benefits, such as improving the efficiency of solar energy systems.
Structural and functional chacterisation of Acot7 in macrophages and its role in inflammation. This project will develop better understanding of the cellular pathways that mediate inflammation and will provide detailed information on a specific enzyme that produces arachidonic acid, the precursor to many inflammatory molecules, and characterisation of novel inhibitory binding sites.
Structural studies on chaperone protein machines from an Antarctic archeon. This project is to understand two fundamental biological processes, protein folding and prevention of RNA folding, that are crucial to all life, in particular, to survival in the cold. The project will determine the structure of the protein folding machine, showing how it works, and determine how RNA is protected after synthesis.
Statistical analyses for spatial organisation in T cell signalling networks. This project aims to reveal how nanoscale spatial organisation encodes plasticity in the T cell signalling network, and how T cells exploit this plasticity to regulate sensitivity to antigens. In adoptive immunity, T cells respond appropriately to any given antigen, but how they make decisions is unclear. This project will define how nanoscale spatial organisation of signalling molecules shapes signalling strength and p ....Statistical analyses for spatial organisation in T cell signalling networks. This project aims to reveal how nanoscale spatial organisation encodes plasticity in the T cell signalling network, and how T cells exploit this plasticity to regulate sensitivity to antigens. In adoptive immunity, T cells respond appropriately to any given antigen, but how they make decisions is unclear. This project will define how nanoscale spatial organisation of signalling molecules shapes signalling strength and plasticity in the T cell antigen receptor (TCR) network; and infer rules linking spatial organisation and signalling activities in intact T cells. Contextualising the TCR signalling network is expected to reveal the origin and use of network plasticity for T cell decision-making. Such information could be invaluable for the design of vaccines and immune-modulating drugs.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160100608
Funder
Australian Research Council
Funding Amount
$359,000.00
Summary
Investigating the structural basis of human antibody stability. This project plans to use protein engineering and X-ray crystallography to investigate the effects of stabilising mutations on antigen binding and the antibody-antigen interaction. Monoclonal antibodies are high-affinity reagents that have transformed the study of biological processes. However, antibodies often display inherent instability, which limits applicability. Mutations have recently been identified that render human antibod ....Investigating the structural basis of human antibody stability. This project plans to use protein engineering and X-ray crystallography to investigate the effects of stabilising mutations on antigen binding and the antibody-antigen interaction. Monoclonal antibodies are high-affinity reagents that have transformed the study of biological processes. However, antibodies often display inherent instability, which limits applicability. Mutations have recently been identified that render human antibodies resistant to aggregation. Preliminary data indicates that stabilising mutations improves the biophysical properties of monoclonals without affecting the native antibody structure. The project aims to provide detailed insights into the molecular basis of antibody stability.Read moreRead less
Investigating the dynamic nature of antibody stability. The aim of the project is to provide insights into the molecular mechanisms of antibody stability. Monoclonal antibodies have transformed the study of biological processes and represent blockbuster therapeutics for cancer and inflammation. Unfortunately, antibodies often display limited stability, which greatly hinders development. Mutations have recently been identified that render human antibodies resistant to aggregation, and high-resolu ....Investigating the dynamic nature of antibody stability. The aim of the project is to provide insights into the molecular mechanisms of antibody stability. Monoclonal antibodies have transformed the study of biological processes and represent blockbuster therapeutics for cancer and inflammation. Unfortunately, antibodies often display limited stability, which greatly hinders development. Mutations have recently been identified that render human antibodies resistant to aggregation, and high-resolution crystal structures are being used to identify function. Intriguingly, preliminary data indicates that the mutations do not affect the native antibody structure, but rather influence dynamic states. The project plans to use a combination of mutagenesis, molecular dynamics simulation and deuterium exchange to study antibody dynamics.Read moreRead less
Structural studies of a reconstructed primordial antigen receptor. Antigen receptors (B- and T-cell receptor) form the basis of the adaptive immune system of humans and all other modern day vertebrates. These complex receptors are believed to have evolved from an extinct homodimeric (symmetrical) ancestor through a process of gene duplication and diversification. However, any molecular insights had so far remained elusive. Using laboratory evolution and X-ray crystallography this project demonst ....Structural studies of a reconstructed primordial antigen receptor. Antigen receptors (B- and T-cell receptor) form the basis of the adaptive immune system of humans and all other modern day vertebrates. These complex receptors are believed to have evolved from an extinct homodimeric (symmetrical) ancestor through a process of gene duplication and diversification. However, any molecular insights had so far remained elusive. Using laboratory evolution and X-ray crystallography this project demonstrates that such a primordial receptor can in principle be reconstructed and characterised. The project proposes to expand this work, which will provide intriguing insights into antigen receptor evolution. The reconstruction of basic recognition modules will also be highly beneficial for biosensor applications. Read moreRead less