A cellular hub for the organisation of T cell priming. This project aims to delineate the cellular interactions involved in the initiation of immune responses by utilising advanced in vivo imaging. Adaptive immunity in vertebrates functions via the acquisition of signals by immune cells via complex interactions with other immune cells, yet these exchanges are difficult to observe and define. This project expects to provide insights into the mechanisms that underpin effective cell-mediated immune ....A cellular hub for the organisation of T cell priming. This project aims to delineate the cellular interactions involved in the initiation of immune responses by utilising advanced in vivo imaging. Adaptive immunity in vertebrates functions via the acquisition of signals by immune cells via complex interactions with other immune cells, yet these exchanges are difficult to observe and define. This project expects to provide insights into the mechanisms that underpin effective cell-mediated immune responses. The expected outcomes are to generate fundamental new knowledge about immune responses and enhance capacity to study the immune system. This could benefit future development of new vaccines and therapies to improve health.Read moreRead less
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
Sphingosine-1-phosphate receptor 5: a novel regulator of T cell immunity. T cells provide critical immune protection against infection and cancer. However, the pathways that regulate these immune cells are not fully understood. T cells express a molecule called S1P5 that has an unknown function in these cells. In this proposal, we reveal new evidence that this molecule is an unappreciated and crucial regulator of T cell behaviour. Using state-of-the-art techniques and novel genetic tools, this p ....Sphingosine-1-phosphate receptor 5: a novel regulator of T cell immunity. T cells provide critical immune protection against infection and cancer. However, the pathways that regulate these immune cells are not fully understood. T cells express a molecule called S1P5 that has an unknown function in these cells. In this proposal, we reveal new evidence that this molecule is an unappreciated and crucial regulator of T cell behaviour. Using state-of-the-art techniques and novel genetic tools, this project aims to discover the involvement of S1P5 in the immune response, and determine how S1P5 can be controlled to enhance protective T cell immunity. The expected outcomes are to generate fundamental new knowledge that will have significance for regulation of the immune response. 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.
The establishment of an immune system that is able to distinguish between self and non-self is of fundamental importance for good health and survival. How this specificity is achieved has been an area of intense investigation for many years because a breakdown of this process leads to the development of autoimmune diseases, such as diabetes, or an inability to fight pathogenic organisms. It has been known for many years that the development T cells, a subset of cells involved in mounting immune ....The establishment of an immune system that is able to distinguish between self and non-self is of fundamental importance for good health and survival. How this specificity is achieved has been an area of intense investigation for many years because a breakdown of this process leads to the development of autoimmune diseases, such as diabetes, or an inability to fight pathogenic organisms. It has been known for many years that the development T cells, a subset of cells involved in mounting immune responses, occurs in the thymus. The thymus produces large numbers of immature T cells (called thymocytes) from which a small number receive the appropriate signals to survive and develop into mature T cells. These tailor-made T cells can then enter the blood and peripheral lymphoid organs where they fight infectious organisms without reacting against host (i.e. self) tissues. The work for this project is aimed at determining how proteins inside thymocytes transmit signals that determine whether thymocytes either survive, and develop into T cells, or are eliminated because they react too strongly with self proteins. We have established that a protein called c-Cbl is central to this process as it regulates the initial strength of the signal that determines the fate of thymocytes. Our aim is to identify the putative key protein regulated by c-Cbl that can sense when a signal is too strong following the binding of a thymocyte to a self protein and directs a cell death signalling response. From this critical point of signal splitting we also aim to identify proteins that relay the death signal to the nucleus where they trigger the production of well-characterised proteins required to mediate cell death. By identifying the proteins in this signalling pathway we will have a greater capacity to control the magnitude of immune responses and therefore be able to lessen tissue damage caused by autoimmune reactions.Read moreRead less
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
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.
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.