Histone deacetylase functions in immune cells. This project aims to define how an enzyme (a histone deacetylase) enables innate immune cells (macrophages) to respond to specific danger signals, such as those activating Toll-like Receptors. To identify processes that provide specificity to signal transduction pathways, this project will characterise protein targets and biological functions of a specific class IIa histone deacetylase in macrophages. This project expects to result in an understandi ....Histone deacetylase functions in immune cells. This project aims to define how an enzyme (a histone deacetylase) enables innate immune cells (macrophages) to respond to specific danger signals, such as those activating Toll-like Receptors. To identify processes that provide specificity to signal transduction pathways, this project will characterise protein targets and biological functions of a specific class IIa histone deacetylase in macrophages. This project expects to result in an understanding of histone deacetylases and protein deacetylation in immune cell responses which can be harnessed to manipulate cell functions for basic science and biotechnology uses.Read moreRead less
An investigation into CD1a, a versatile antigen-presenting molecule. This project aims to investigate how T lymphocytes are activated by lipids presented by the skin-associated antigen-presenting molecule, CD1a. Using X-ray crystallography and cellular immunology, we will provide fundamental insight into this poorly understood immunological axis. We will determine the molecular basis for how CD1a presents diverse self and foreign lipids, and how such CD1a-lipid complexes are recognised by the r ....An investigation into CD1a, a versatile antigen-presenting molecule. This project aims to investigate how T lymphocytes are activated by lipids presented by the skin-associated antigen-presenting molecule, CD1a. Using X-ray crystallography and cellular immunology, we will provide fundamental insight into this poorly understood immunological axis. We will determine the molecular basis for how CD1a presents diverse self and foreign lipids, and how such CD1a-lipid complexes are recognised by the responding T cells. This basic science discovery project will provide substantial new knowledge in the burgeoning field of lipid-mediated immunity, which should ultimately lead to new therapies targeting the CD1a lipid display molecule to either prevent immune mediated damage or promote protective immunity as required.Read moreRead less
Deciphering novel cross-talk between innate cytokine receptors. Understanding the basic functions of interferons, how they signal to cells, is central to understanding fundamental immunity. Interferons are crucial molecules of the immune system that are important for normal cell development and they protect the body from viral infection and cancer but can be deleterious in different autoimmune diseases and trauma settings. Preliminary Data shows there is a pathway of interferon signalling that h ....Deciphering novel cross-talk between innate cytokine receptors. Understanding the basic functions of interferons, how they signal to cells, is central to understanding fundamental immunity. Interferons are crucial molecules of the immune system that are important for normal cell development and they protect the body from viral infection and cancer but can be deleterious in different autoimmune diseases and trauma settings. Preliminary Data shows there is a pathway of interferon signalling that has previously been overlooked. This project aims to understand how this pathway works and how it contributes to the normal workings of cells. This fundamental science has future consequences for the design of vaccines and for the design of therapeutics to treat diseases that show defective interferon signalling.Read moreRead less
Mechanisms connecting diet, metabolism, gut microbiota and immunity. This project will identify the role of short chain fatty acids and the G-protein coupled receptor (GPR43) in regulating immune responses. This could explain how diet affects immune responses and also how certain bacteria in the gut provide benefits for immune defence.
A novel axis of cooperation between innate and adaptive immunity. The project aims to understand how two molecular components of the immune system, Complement and MHC, cooperate to protect the host. Further, these two molecules mediate trogocytosis, a little-studied form of intercellular communication, between two major immune cell types: dendritic cells and B cells. The project will be multidisciplinary, applying high-end microscopy, biochemistry, cell biology and immunology techniques. Person ....A novel axis of cooperation between innate and adaptive immunity. The project aims to understand how two molecular components of the immune system, Complement and MHC, cooperate to protect the host. Further, these two molecules mediate trogocytosis, a little-studied form of intercellular communication, between two major immune cell types: dendritic cells and B cells. The project will be multidisciplinary, applying high-end microscopy, biochemistry, cell biology and immunology techniques. Personnel will be trained in cutting-edge techniques. The project will expand knowledge on basic immunology and cell-cell cooperation. It will generate intellectual property for the biotechnology sector to develop new commercial products that might improve the health of humans and also animals of economic importance.Read moreRead less
The role of a novel protein, interferon epsilon, in reproductive tract immunity. This project aims to develop a world-first description of a new protein that has a protective role against female reproductive tract infections. This unique protein, called interferon epsilon, was discovered in our laboratory. This project will facilitate development of new therapeutic approaches of benefit in diseases such as Chlamydia and Herpes Simplex Virus.
Elucidating the post-transcriptional regulation of mast cell proteases. Mast cells (MCs) are immune cells that protect against pathogens but may induce deleterious inflammation. MC function is mediated by specific proteases that are pre-formed and stored in granules. These proteases have unique yet poorly understood mechanisms of regulation. The aim of the project is to use a novel suite of molecular tools and genetically modified mice to identify the critical regions of transcripts that post-tr ....Elucidating the post-transcriptional regulation of mast cell proteases. Mast cells (MCs) are immune cells that protect against pathogens but may induce deleterious inflammation. MC function is mediated by specific proteases that are pre-formed and stored in granules. These proteases have unique yet poorly understood mechanisms of regulation. The aim of the project is to use a novel suite of molecular tools and genetically modified mice to identify the critical regions of transcripts that post-transcriptionally regulate the production and storage of these proteins. The project aims to identify the RNA binding proteins, microRNAs and other novel factors that also regulate them. This is expected to elucidate the post-transcriptional mechanisms of regulation of MC proteases.Read moreRead less
Why do neutrophils swarm? This project aims to combine novel immunology, microscopy and computational approaches to investigate how immune cells called neutrophils cooperate to protect the host against microbes. Neutrophils are rapidly recruited to sites of inflammation and then utilise a type of highly coordinated collective behaviour termed swarming. However, the role of neutrophil swarms in fighting off infection is poorly understood. The project is poised to generate new knowledge on the imp ....Why do neutrophils swarm? This project aims to combine novel immunology, microscopy and computational approaches to investigate how immune cells called neutrophils cooperate to protect the host against microbes. Neutrophils are rapidly recruited to sites of inflammation and then utilise a type of highly coordinated collective behaviour termed swarming. However, the role of neutrophil swarms in fighting off infection is poorly understood. The project is poised to generate new knowledge on the importance of immune cell cooperation by developing in silico models of the immune response. The project will provide benefit through enhanced understanding of fundamental principles of immunity and develop new computational tools to model complex immune function in silico.Read moreRead less
Combating invading DNA: a process conserved in evolution? Cells of our body defend against foreign genetic material, or DNA, which indicates an infection or invading DNA capable of causing mutation. These defences are so important that several layers have developed during evolution, and this project compares the responses of different organisms to foreign DNA.