Structural studies of host-pathogen interactions. The host-pathogen interface represents a major frontier for biomedical and biotechnological applications. This project aims to understand at the atomic level two such interfaces. In the first instance, the project will elucidate the molecular basis for inhibition of premature host cell death by poxviruses, in particular vaccinia and variola virus, the causative agent of smallpox. In the second instance, the aim is to understand how defensins, a ....Structural studies of host-pathogen interactions. The host-pathogen interface represents a major frontier for biomedical and biotechnological applications. This project aims to understand at the atomic level two such interfaces. In the first instance, the project will elucidate the molecular basis for inhibition of premature host cell death by poxviruses, in particular vaccinia and variola virus, the causative agent of smallpox. In the second instance, the aim is to understand how defensins, a major class of host defence molecules, recognise microbial targets such as fungi, and exert a potent antimicrobial effect. Understanding the precise molecular mechanisms operating at both these host-pathogen interfaces this will provide novel avenues for the design of antiviral and antimicrobial agents.Read moreRead less
The ins and outs of HIV biology. This project aims to delineate the fundamental mechanisms that regulate the production of HIV and the ability of HIV to cause AIDS in infected patients. It will utilise state-of-the-art technologies to unearth new clues that govern the biology of HIV, with the ultimate goal to develop novel vaccine and treatment strategies against HIV.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100090
Funder
Australian Research Council
Funding Amount
$640,000.00
Summary
A centre for structural cryo-electron microscopy. This equipment will use powerful microscopes to visualise the shape of proteins. The data generated in the facility will provide fundamental insight into how large complex proteins govern life-and-death events in biology. These data will be important for scientists to develop new approaches to control aberrant protein function in disease.
Structural analysis of poxviruses: advancing our understanding of complex DNA viruses and their in vivo crystals. This project will use innovative structural biology approaches to investigate two key particles of poxviruses, the largest viruses infecting humans. Advance in understanding of immature particles and natural crystals of poxviruses will provide the basis for the development of broad-spectrum antivirals and novel microparticles for vaccine-delivery.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100152
Funder
Australian Research Council
Funding Amount
$360,000.00
Summary
Melbourne and La Trobe rapid integrated X-ray diffraction facility. This new facility will enable rapid X-ray diffraction studies of macromolecular crystals which are critical in reaching an understanding of cellular signalling events and interactions between microbial pathogens and their host organisms at the atomic level.
Understanding how pore-forming proteins punch holes in membranes. This project aims to unravel missing molecular details of how a major superfamily of proteins is able to drill holes in cell membranes. Animals, plants, fungi and bacteria all use pore-forming proteins as cell-killing weapons of mass destruction. Despite their lethal nature and their roles in infection and immunity, how these proteins work remains enigmatic. Project outcomes could reveal novel mechanisms general to these essential ....Understanding how pore-forming proteins punch holes in membranes. This project aims to unravel missing molecular details of how a major superfamily of proteins is able to drill holes in cell membranes. Animals, plants, fungi and bacteria all use pore-forming proteins as cell-killing weapons of mass destruction. Despite their lethal nature and their roles in infection and immunity, how these proteins work remains enigmatic. Project outcomes could reveal novel mechanisms general to these essential proteins and provide fundamental insights in understanding vital physiological processes across all kingdoms of life. Ultimately, the knowledge gained may prove useful in the engineering of membrane pores as highly specific sensors for a variety of molecules with nanotechnology and biotechnology applications.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
Spindles of insect viruses: structure, function and engineering of natural protein crystals as microparticles for vaccine delivery. Protein self-assembly is a critical process participating to the cell architecture and molecular machinery. This project will study the molecular structure of crystals forming in virally-infected cells, a striking example of protein self-assembly, and will engage in engineering of novel crystalline microparticles as antiviral vaccines.
Mechanism of action of a novel multifunctional bacterial secretion system. This project aims to examine the functional role of holin/lysin secretion systems in the complex lifestyles of important animal bacterial pathogens. This project will generate new knowledge in how bacteria interact with each other, the environment or their hosts through the secretion of proteins or other particles. The results of this research will provide a deeper understanding of the multifunctional roles that these un ....Mechanism of action of a novel multifunctional bacterial secretion system. This project aims to examine the functional role of holin/lysin secretion systems in the complex lifestyles of important animal bacterial pathogens. This project will generate new knowledge in how bacteria interact with each other, the environment or their hosts through the secretion of proteins or other particles. The results of this research will provide a deeper understanding of the multifunctional roles that these unusual secretion systems play and how they contribute to niche adaptation and disease. New insights will lead to identifying targets for future veterinary disease interventions or biotechnological applications.Read moreRead less
The mechanism of pore formation by Membrane Attack Complex/Perforin-like proteins. Members of the Membrane Attack Complex / Perforin (MACPF) family of proteins are essential for life, playing fundamental roles in immunity, tissue development and neuron formation. This project seeks to understand the basic mechanism of how MACPF proteins can form pores in target cells, a process central for killing in mammalian immunity.