Linking sex-specific adaptation to the evolution of infectious disease. This project aims to examine how differences in the response of males and females to pathogen attack can influence the evolution of infectious disease. This project expects to generate new knowledge in the area of host-pathogen co-evolution, by integrating approaches from the fields of evolutionary genetics, sexual selection, and epidemiology. Expected outcomes include an enhanced capacity to build interdisciplinary collabor ....Linking sex-specific adaptation to the evolution of infectious disease. This project aims to examine how differences in the response of males and females to pathogen attack can influence the evolution of infectious disease. This project expects to generate new knowledge in the area of host-pathogen co-evolution, by integrating approaches from the fields of evolutionary genetics, sexual selection, and epidemiology. Expected outcomes include an enhanced capacity to build interdisciplinary collaborations and development of theory that predicts infection dynamics in any species with separate sexes. This is expected to provide significant benefits, such as improving our knowledge of why the sexes differ and potentially providing new avenues for understanding disease outbreaks and preventing population declines or extinctions.Read moreRead less
Activation of invasion in Toxoplasma. Host cell invasion is critical for the establishment and maintenance of infection by the single-celled parasite Toxoplasma gondii, the causative agent of Toxoplasmosis. This project will use the latest molecular techniques to understand how invasion is activated and will define a new set of drug targets to treat Toxoplasmosis and related diseases.
Molecular dissection of malaria parasite motility and host-cell invasion across the lifecycle. Malaria parasites move in a unique way, gliding across cell surfaces and infecting host cells using a unique molecular motor. This research aims to understand the molecular mechanics behind parasite movement and use this to develop novel drugs that might throw a spanner in the parasite motor, blocking movement and thereby preventing malaria disease.
Imaging the generation and recall of protective antiviral immune responses in vivo. Our understanding of the in vivo dynamics of cellular immune responses to infectious diseases is poor. This project will utilise advanced intravital imaging combined with novel tools to dissect the cellular events involved in the generation and recall of T cell responses to localised virus infection, combined with a detailed functional analysis of the lymphoid organ stroma. Such fundamental information will contr ....Imaging the generation and recall of protective antiviral immune responses in vivo. Our understanding of the in vivo dynamics of cellular immune responses to infectious diseases is poor. This project will utilise advanced intravital imaging combined with novel tools to dissect the cellular events involved in the generation and recall of T cell responses to localised virus infection, combined with a detailed functional analysis of the lymphoid organ stroma. Such fundamental information will contribute to the development of new generation vaccines and therapies to protect against tissue-specific infectious diseases, cancers and autoimmune diseases.Read moreRead less
The function and misfunction of serum apolipoproteins: lipid binding and protein misfolding. The interaction between proteins and lipids is a fundamental aspect of cellular processes in all organisms. Lipid binding proteins must be structurally dynamic to perform their function, which predisposes them to misfolding and aggregation. This project aims to assess the structural mechanisms of lipid binding by apolipoproteins, and how these proteins balance this function with their propensity to misfo ....The function and misfunction of serum apolipoproteins: lipid binding and protein misfolding. The interaction between proteins and lipids is a fundamental aspect of cellular processes in all organisms. Lipid binding proteins must be structurally dynamic to perform their function, which predisposes them to misfolding and aggregation. This project aims to assess the structural mechanisms of lipid binding by apolipoproteins, and how these proteins balance this function with their propensity to misfold. It will focus on apolipoprotein (apo)A-I as a model serum apolipoprotein that binds lipids and mediates lipid transport in circulation. This project also aims to provide an important new understanding of protein-lipid interactions, the structural mechanisms of apolipoproteins, and the process of misfolding in a diverse range of proteins.Read moreRead less
Understanding the biogenesis of exosomes. This project aims to understand how exosomes are made in human cells. Exosomes are small packages that are released by cells, which mediate communication between cells. Currently, very little is known about how exosomes are made within a cell. This project expects to identify key proteins that are involved in the production of exosomes and to understand exosomes synthesis, thereby expanding our knowledge on how cells regulate communication signals. Disse ....Understanding the biogenesis of exosomes. This project aims to understand how exosomes are made in human cells. Exosomes are small packages that are released by cells, which mediate communication between cells. Currently, very little is known about how exosomes are made within a cell. This project expects to identify key proteins that are involved in the production of exosomes and to understand exosomes synthesis, thereby expanding our knowledge on how cells regulate communication signals. Dissecting how exosomes are produced at the fundamental level will provide significant benefits such as a deeper understanding of how cells maintain normal cellular functions.Read moreRead less
The discovery and characterisation of novel protein regulators of blood cell formation. All of the mature blood cells in the human body are derived from a common ancestor cell type known as a stem cell. Our proposed studies will enhance our knowledge of how functional, mature blood cells are formed from stem cells and how dysregulation of these normally tightly controlled pathways can give rise to severe blood diseases.
Cellular Organisation of Protective Immune Responses. Our immune system consists of a task force of white blood cells that coordinate to defeat invading pathogens. Research has revealed a cell receptor, CXCR3, controls immune cell interactions, which determine immune control and protection during initial cell activation and viral infection. This project will use a multi-disciplinary approach combining viral immunology, unique mouse models, advanced imaging, and bioinformatic analyses to dissect ....Cellular Organisation of Protective Immune Responses. Our immune system consists of a task force of white blood cells that coordinate to defeat invading pathogens. Research has revealed a cell receptor, CXCR3, controls immune cell interactions, which determine immune control and protection during initial cell activation and viral infection. This project will use a multi-disciplinary approach combining viral immunology, unique mouse models, advanced imaging, and bioinformatic analyses to dissect the cellular conversations that underpin immune protection. Revealing the mechanisms of cellular interactions during an immune response will have a major impact on development of targeted vaccines, and therapeutics (particularly for chronic infections and cancer), which are major health burdens.Read moreRead less
New molecular tools to study the mechanisms of bacterial metal homeostasis. This project aims to provide new insight into how metal ion uptake is regulated. It will precisely measure the cellular concentrations of metal ions, reveal the roles of metal ions in essential cellular processes, and identify the molecular targets of metal toxicity. Metal ions are essential to all forms of life and are used by up to half of all proteins to facilitate cellular chemical processes. The intended outcome of ....New molecular tools to study the mechanisms of bacterial metal homeostasis. This project aims to provide new insight into how metal ion uptake is regulated. It will precisely measure the cellular concentrations of metal ions, reveal the roles of metal ions in essential cellular processes, and identify the molecular targets of metal toxicity. Metal ions are essential to all forms of life and are used by up to half of all proteins to facilitate cellular chemical processes. The intended outcome of the research is to provide new fundamental knowledge of the roles of metal ions in bacterial cells; knowledge that will be key to defining the chemical biology of living systems and will provide information essential to understanding how microbes adapt to changing environments.Read moreRead less
Untangling the plant Golgi apparatus: Functional proteomics to understand plant cell wall biosynthesis. The plant cell wall determines plant morphology and structure. It is also a major factor in food quality, and it is used as forage and is the raw material for a range of industries. A significant proportion of the cell wall is synthesised in a poorly studied cellular compartment known as the Golgi apparatus. This project intends to exploit unique isolation and analytical techniques in conjunct ....Untangling the plant Golgi apparatus: Functional proteomics to understand plant cell wall biosynthesis. The plant cell wall determines plant morphology and structure. It is also a major factor in food quality, and it is used as forage and is the raw material for a range of industries. A significant proportion of the cell wall is synthesised in a poorly studied cellular compartment known as the Golgi apparatus. This project intends to exploit unique isolation and analytical techniques in conjunction to further profile and characterise this structure in order to uncover new information about the complex interplay of components involved in plant cell wall biosynthesis. This information will be used to support approaches to manipulate cell walls to produce plant biomass optimised for agricultural and industrial applications.Read moreRead less