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
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
Pore-forming toxins: more than one way to make a hole. 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. This project aims to unravel missing molecular details of how a major superfamily of such proteins is able to drill holes in cell membranes. The outcomes could reveal novel mechanisms general to these proteins and provid ....Pore-forming toxins: more than one way to make a hole. 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. This project aims to unravel missing molecular details of how a major superfamily of such proteins is able to drill holes in cell membranes. 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.
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The structural basis for defensin-mediated membrane attack. This project aims to define how the innate defense proteins called defensins attack target membranes to cause cells to burst and die. It is often said that attack is the best form of defense, and the immune systems of plants and animals will often target the cell membranes of microbes and other pathogens to defend themselves. This project will identify the precise molecular mechanism underlying defensin activity, and clarify how ligand ....The structural basis for defensin-mediated membrane attack. This project aims to define how the innate defense proteins called defensins attack target membranes to cause cells to burst and die. It is often said that attack is the best form of defense, and the immune systems of plants and animals will often target the cell membranes of microbes and other pathogens to defend themselves. This project will identify the precise molecular mechanism underlying defensin activity, and clarify how ligand recognition and subsequent multimerisation leads to target membrane lysis. The project will establish the fundamental mechanisms regulating antimicrobial defense systems based on small proteins, and define a conceptual framework for the action of defensins to develop strategies to combat fungal infections.Read moreRead less
The structural biology of trace metal trafficking across membranes. This project aims to investigate how essential trace element nutrients are recognised and specifically acquired and expelled by bacterial cells. Cells are surrounded by biomembranes that separate and protect them from their environments. Embedded within these membranes are proteins that perform essential functions. In bacteria, membrane proteins are responsible for the uptake and elimination of trace elements that are required f ....The structural biology of trace metal trafficking across membranes. This project aims to investigate how essential trace element nutrients are recognised and specifically acquired and expelled by bacterial cells. Cells are surrounded by biomembranes that separate and protect them from their environments. Embedded within these membranes are proteins that perform essential functions. In bacteria, membrane proteins are responsible for the uptake and elimination of trace elements that are required for survival. This project will investigate the features of integral membrane proteins that allow discrimination between cargo, by defining their three dimensional architectures using X-ray crystallography. This will contribute to the field of membrane protein structural biology and fundamental discoveries in the area of cellular trace element homeostasis and toxicity.Read moreRead less
How do signals cross the cell membrane: the betacommon receptor family. This project aims to unravel missing molecular details of how a family of proteins, called the betacommon receptors, is able to signal across cell walls. This project aims to generate new knowledge about how membrane-bound receptors transmit biological signals in living organisms. Despite their fundamental importance in biology, how these proteins work remain enigmatic. Expected outcomes include discovery of novel mechanisms ....How do signals cross the cell membrane: the betacommon receptor family. This project aims to unravel missing molecular details of how a family of proteins, called the betacommon receptors, is able to signal across cell walls. This project aims to generate new knowledge about how membrane-bound receptors transmit biological signals in living organisms. Despite their fundamental importance in biology, how these proteins work remain enigmatic. Expected outcomes include discovery of novel mechanisms general to these types of protein receptors and fundamental insights in understanding vital physiological processes across all kingdoms of life. Ultimately, this new knowledge should benefit efforts to discover novel treatments in cases where malfunctioning receptors cause diseases in animals and humans.Read moreRead less