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
Nanopore sensors for multiplexed, ultra-fast gene detection. The aim of this research is to develop the application of protein nanopores for multiplex identification of DNA samples for ultrafast gene detection. This is a type of barcoding of organism DNA that allows for rapid gene identification. This technology aims to address a significant need for rapid, on-the-spot identification of organisms. Applications include rapid identification of pathogenic bacteria in infections and identification o ....Nanopore sensors for multiplexed, ultra-fast gene detection. The aim of this research is to develop the application of protein nanopores for multiplex identification of DNA samples for ultrafast gene detection. This is a type of barcoding of organism DNA that allows for rapid gene identification. This technology aims to address a significant need for rapid, on-the-spot identification of organisms. Applications include rapid identification of pathogenic bacteria in infections and identification of organisms in environmental sampling. Current methods are relative slow, require DNA amplification and specialised laboratories.
This proposal aims to fine tune the properties of the large nanopore, polyC9, with respect to size and charge, as well as to identify and characterise novel large nanopores. Read moreRead less
Hitting bacteria with a Bam: Lectin-Like Antimicrobials as New Antibiotics. Antibiotic resistance in disease-causing bacteria is a rapidly growing problem, making the development of new antibiotics of critical importance. This project aims to develop naturally produced lectin-like protein antibiotics as novel antimicrobial agents. To achieve this, the project will produce an extensive library of these antibiotics and test them for potency and specificity. Using cutting-edge techniques, it will d ....Hitting bacteria with a Bam: Lectin-Like Antimicrobials as New Antibiotics. Antibiotic resistance in disease-causing bacteria is a rapidly growing problem, making the development of new antibiotics of critical importance. This project aims to develop naturally produced lectin-like protein antibiotics as novel antimicrobial agents. To achieve this, the project will produce an extensive library of these antibiotics and test them for potency and specificity. Using cutting-edge techniques, it will determine how these antibiotics kill cells on a molecular and cellular level. It is anticipated this research will create the tools and knowledge required to exploit lectin-like protein antibiotics to fight bacterial infection, which will lead to their use in the prevention of crop and livestock losses due to disease.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.
All in the family: understanding a new class of bacterial toxins. 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. The outcomes could reveal novel mechanisms general to these proteins and ....All in the family: understanding a new class of bacterial toxins. 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. The outcomes could reveal novel mechanisms general to these proteins and provide fundamental insights in understanding vital physiological processes across all kingdoms of life. Ultimately, this knowledge may guide the design of artificial protein pores that are selective for specific molecules with applications such as measuring metal ions, sugars, pesticides or pollutants. Read moreRead less
The structural basis for MPEG1 mediated assembly of immune complexes. Macrophage Expressed Gene-1 (MPEG1) is an ancient pore forming perforin-like immune effector that is found throughout multicellular life. In humans MPEG1 is found in Macrophages (a type of immune cell) and functions to eliminate a wide range of different infectious microbes. In this study we will study how different modifications and molecular interactions drive MPEG1 function. Crucially our work will provide a framework to ....The structural basis for MPEG1 mediated assembly of immune complexes. Macrophage Expressed Gene-1 (MPEG1) is an ancient pore forming perforin-like immune effector that is found throughout multicellular life. In humans MPEG1 is found in Macrophages (a type of immune cell) and functions to eliminate a wide range of different infectious microbes. In this study we will study how different modifications and molecular interactions drive MPEG1 function. Crucially our work will provide a framework to understand how MPEG1 interacts with the interferon signalling pathway. These data will provide fundamental insight into how perforin-like proteins are controlled and will broadly inform new approaches to modify immune function and molecular signalling events.Read moreRead less
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.