Defining the immunological roles of stromal cells within lymphoid tissues. The populations of endothelial and mesenchymal cells that construct the lymphoid tissues are being revealed as key players in the priming and orchestration of immune responses. Yet, fundamental knowledge of the molecular makeup and the functions of these stromal cells, particularly their roles in immune responses, is sorely lacking. This project will utilise a multidisciplinary approach including advanced imaging and bioi ....Defining the immunological roles of stromal cells within lymphoid tissues. The populations of endothelial and mesenchymal cells that construct the lymphoid tissues are being revealed as key players in the priming and orchestration of immune responses. Yet, fundamental knowledge of the molecular makeup and the functions of these stromal cells, particularly their roles in immune responses, is sorely lacking. This project will utilise a multidisciplinary approach including advanced imaging and bioinformatics to dissect the functions of the lymphoid stromal cells and their roles in the swelling of lymphoid tissues during immune responses. This will provide vital information about the biology of these understudied cells and reveal the ways in which they support the generation of immunity.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.
Elucidating the regulation of cell death by random mutagenesis of key apoptotic proteins. All organisms need to remove damaged or excessive cells. This cell death process is called apoptosis. Defects in apoptosis result in numerous diseases including cancer, and neurodegenerative and immune disorders. Determining how this process is regulated is of crucial importance for therapeutic intervention. We will utilise a powerful strategy to mutate proteins required for apoptosis so that they no longer ....Elucidating the regulation of cell death by random mutagenesis of key apoptotic proteins. All organisms need to remove damaged or excessive cells. This cell death process is called apoptosis. Defects in apoptosis result in numerous diseases including cancer, and neurodegenerative and immune disorders. Determining how this process is regulated is of crucial importance for therapeutic intervention. We will utilise a powerful strategy to mutate proteins required for apoptosis so that they no longer work, which will allow the identification of protein regions essential for cell death activity . This will lead to identification of potential drug targets to control apoptosis. Elucidating the mechanism of cell death will lead to the development of novel and improved therapies for diseases such as cancer and neurodegenerative disease.Read moreRead less
Understanding the life and death of Mucosal-associated invariant T cells. Cell death of naïve T cells in lymphoid organs is well-understood. However, T cells only gain their function upon activation, and how activated T cells regulate their life or death remains unclear. Mucosal-associated Invariant T (MAIT) cells are abundant in non-lymphoid tissues as key local players in immunity, and share some features of activated conventional T cells. This project aims to define how MAIT cell survival and ....Understanding the life and death of Mucosal-associated invariant T cells. Cell death of naïve T cells in lymphoid organs is well-understood. However, T cells only gain their function upon activation, and how activated T cells regulate their life or death remains unclear. Mucosal-associated Invariant T (MAIT) cells are abundant in non-lymphoid tissues as key local players in immunity, and share some features of activated conventional T cells. This project aims to define how MAIT cell survival and death are controlled. It combines methods we developed to track MAIT cells in vivo with expertise in cell death analysis. This project is expected to elucidate the complex mechanisms controlling MAIT cell survival/death and increase our fundamental understanding of cell death mechanisms of activated T cells.Read moreRead less
Role of the PU.1 transcription factor in regulating lymphoid development. Haemopoiesis is a tightly regulated process and provides an important model for our understanding and application of stem cell biology. Perturbation of early haemopoiesis results in a number of important disorders including leukaemia, anaemia and immunodeficiency. The application of stem cells to many disease conditions is currently being pursued, however, in order to develop therapeutic interventions knowledge of normal c ....Role of the PU.1 transcription factor in regulating lymphoid development. Haemopoiesis is a tightly regulated process and provides an important model for our understanding and application of stem cell biology. Perturbation of early haemopoiesis results in a number of important disorders including leukaemia, anaemia and immunodeficiency. The application of stem cells to many disease conditions is currently being pursued, however, in order to develop therapeutic interventions knowledge of normal cellular differentiation is crucial. The studies outlined here aim to contribute to the understanding of the these processes and hence help to provide the framework for future studies aimed at more directly altering cell fate decision for clinical applications. Read moreRead less
An X-ray crystallographic investigation into co-receptors on T-lymphocytes. T lymphocytes are an indispensable cellular component of the immune system. The normal process of T cell selection in the thymus, and the ability of mature T cells to respond to foreign antigens are governed by receptor recognition and co-receptor mediated events. The co-receptors encompass a wide spectrum of structurally diverse proteins that are involved in adhesion, co-ligation and signal transduction. This proposa ....An X-ray crystallographic investigation into co-receptors on T-lymphocytes. T lymphocytes are an indispensable cellular component of the immune system. The normal process of T cell selection in the thymus, and the ability of mature T cells to respond to foreign antigens are governed by receptor recognition and co-receptor mediated events. The co-receptors encompass a wide spectrum of structurally diverse proteins that are involved in adhesion, co-ligation and signal transduction. This proposal aims to investigate, using X-ray crystallography as the primary research tool, co- receptors located on T-lymphocytes. This work will gain fundamental insights into co-receptor function.Read moreRead less
Controlling apoptotic cell death in health and disease. Regulating how and when cells die is crucial for the development and maintenance of a healthy body and mind. This project will investigate the proteins that are responsible for controlling cell death with the view to identifying novel ways to target these proteins for the treatment of disorders such as cancer, neurodegenerative disease and autoimmunity.
New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based intervent ....New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based interventions and vaccines that protect the gut and lung from infectious and inflammatory issues. The harnessing of effective immune responses to control such challenges, are of enormous fundamental and long-standing biological interest, and are amongst the most important areas of current scientific research.Read moreRead less
Molecular mechanisms of cyclic Adenosine Monophosphate (AMP) induced apoptosis. Cyclic Adenosine Monophosphate (cAMP) is an important cellular chemical necessary for cell growth. However, de-regulated cAMP production in response to altered physiology can result in cellular death or apoptosis. This is attributed to the development of certain human diseases and this project aims to understand the molecular mechanism behind this process.
Designing new generation adjuvants for allergy and parasite vaccines. Allergy vaccines have the potential to provide a permanent cure against many allergic diseases, currently affecting 20-30 per cent of people in developed countries. This project will study how allergy vaccines work and how we can improve their effectiveness and safety.