The role of immuno-exosomes in innate immunity. This project aims to determine the role of exosomes (EV) in innate immunity. Exosomes are extracellular vesicles secreted by mammalian cells that have an important biological function in intercellular communication by transferring biologically active proteins, lipids, and RNAs to neighbouring or distant cells. Following exposure to a foreign organism, cells dynamically change the protein composition of the EV they secrete. While this data supports ....The role of immuno-exosomes in innate immunity. This project aims to determine the role of exosomes (EV) in innate immunity. Exosomes are extracellular vesicles secreted by mammalian cells that have an important biological function in intercellular communication by transferring biologically active proteins, lipids, and RNAs to neighbouring or distant cells. Following exposure to a foreign organism, cells dynamically change the protein composition of the EV they secrete. While this data supports a role for EV as key players in innate immunity, a full understanding of the biological relevance of these vesicles and how they serve as a cellular defence mechanism is lacking. This project will provide significant benefits such as addressing key questions in EV biology and providing new fundamental insights into a novel and poorly understood component of the innate immune response.Read moreRead less
Molecular Mechanisms of NOD signalling. Alterations in NOD1 and NOD2 (nucleotide-binding oligomerization domain containing 1 and 2) signalling have been implicated in various human inflammatory diseases. Therefore, a clear understanding of the molecular signalling pathways is important to gain further insights into potential drug targets for the treatment of these diseases. Using novel experimental approaches, this project aims to identify new members of the NOD signalling pathway. It will test ....Molecular Mechanisms of NOD signalling. Alterations in NOD1 and NOD2 (nucleotide-binding oligomerization domain containing 1 and 2) signalling have been implicated in various human inflammatory diseases. Therefore, a clear understanding of the molecular signalling pathways is important to gain further insights into potential drug targets for the treatment of these diseases. Using novel experimental approaches, this project aims to identify new members of the NOD signalling pathway. It will test the effect of pharmacological inhibition of established molecules such as RIPK2 or IAPs in NOD dependent models for human diseases. Outcomes of this study will be of the utmost interest for the treatment of NOD driven diseases such as Crohn's disease, Blau syndrome or asthma.Read moreRead less
Toll-like receptors in infectious and inflammatory diseases: the double-edged sword of innate immunity. The innate immune system is the first line of defence against invading microorganisms. This project will explore the role of specific innate immune genes in the control of infections and the development of inflammatory diseases.
Investigating the actions of anti-inflammatory pathways in chronic lung disease. There is an urgent need to develop better drugs for Chronic Obstructive Pulmonary Disease (COPD) as patients become resistant to currently used anti-inflammatory drugs with disease progression. This research will uncover fundamental biology into an important class of anti-inflammatory receptor termed ALX/FPR2. This receptor normally coordinates the clearance of infection and injured tissue and subsequently switches ....Investigating the actions of anti-inflammatory pathways in chronic lung disease. There is an urgent need to develop better drugs for Chronic Obstructive Pulmonary Disease (COPD) as patients become resistant to currently used anti-inflammatory drugs with disease progression. This research will uncover fundamental biology into an important class of anti-inflammatory receptor termed ALX/FPR2. This receptor normally coordinates the clearance of infection and injured tissue and subsequently switches off inflammation. Essential knowledge into why this receptor pathway fails to switch off inflammation will be determined. Furthermore, the development of targeting strategies to this receptor represents an innovative approach to blocking damaging and chronic airway inflammation.Read moreRead less
Inflammasomes: molecular drivers of anti-microbial defence. The innate immune system is the body’s first line of defence against infection, but also drives unhealthy inflammation. Families of innate immune receptors, such as nucleotide-binding oligomerisation domain (NOD-like Receptors), were recently discovered to control both anti-microbial defence and unhealthy inflammation. This project will characterise the basic biology of NOD-like Receptors at the molecular, cellular and organismal levels ....Inflammasomes: molecular drivers of anti-microbial defence. The innate immune system is the body’s first line of defence against infection, but also drives unhealthy inflammation. Families of innate immune receptors, such as nucleotide-binding oligomerisation domain (NOD-like Receptors), were recently discovered to control both anti-microbial defence and unhealthy inflammation. This project will characterise the basic biology of NOD-like Receptors at the molecular, cellular and organismal levels, and will thereby lead to a greater understanding of the fundamental biological pathways controlling inflammation and defence against infection. This may ultimately lead to commercial opportunities for treating infection and chronic inflammation.Read moreRead less
The regulation of anti-viral immunity by host and viral proteins. Anti-viral immunity is initially triggered when specific immune sensors detect viral components within the cell. This project will use a combined functional/structural approach to investigate the specifics of immune activation by a pivotal immune sensor and use this information to understand how influenza A sabotages this specific immune response.
The role of P2X7 and P2X4 receptor mediated innate phagocytosis in pathogenesis and treatment of neurodegenerative diseases. This project will identify how inherited variation in two proteins of the brain can accelerate the removal of neurones and predispose to a range of neurodegenerative diseases. Knowledge of the biological basis of this finding will allow a search for new compounds which will slow and protect against this form of neurodegeneration.
Investigating the role of the innate immune complement system in the abnormal development of the central nervous system. Past research has discovered a surprising link between the immune system, dietary folate deficiency and the development of the embryonic brain. This project will investigate the immune system in the developing brain, in order to understand the causes of developmental defects such as neural tube defects, and the role dietary folate plays in this process.
Recognition of lipid antigens by the immune system. T cells are a critical component of the immune system, protecting against a range of pathogens by detecting and responding to foreign molecules. Despite their importance, there is still much to learn about how T cells function. New types of T cells that respond to bacteria-derived lipid molecules, have recently been identified. This project aims to undertake a molecular and functional investigation into lipid-reactive T cells. This will provide ....Recognition of lipid antigens by the immune system. T cells are a critical component of the immune system, protecting against a range of pathogens by detecting and responding to foreign molecules. Despite their importance, there is still much to learn about how T cells function. New types of T cells that respond to bacteria-derived lipid molecules, have recently been identified. This project aims to undertake a molecular and functional investigation into lipid-reactive T cells. This will provide basic fundamental insight into a poorly understood, but crucial, component of the immune system as well as an opportunity to ultimately develop novel lipid-based vaccines.Read moreRead less
A molecular and functional investigation of innate-like T cells of the immune system. This project will investigate innate-like T cells, which are at a crossroad between innate and adaptive immunity. A complete knowledge of the cellular function and balance of these cells will offer potential for new immunotherapies associated with infectious and autoimmune disorders.