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
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
Neural migration: Which cells advance and which stay behind? This project aims to examine the neural crest cells that colonise the developing gut and to identify why some cells advance while others stay behind to populate a region. Directed cell migration is essential for normal development, including for the nervous system. In most of the migratory cell populations that have been analysed to date, all of the cells migrate as a collective from one location to another. However, there are also mi ....Neural migration: Which cells advance and which stay behind? This project aims to examine the neural crest cells that colonise the developing gut and to identify why some cells advance while others stay behind to populate a region. Directed cell migration is essential for normal development, including for the nervous system. In most of the migratory cell populations that have been analysed to date, all of the cells migrate as a collective from one location to another. However, there are also migratory cell populations that must populate the areas through which they migrate, and thus some cells get left behind while others advance. The planned data are likely to be relevant to other cell populations that also populate the areas through which they migrate, including neural crest-derived melanocytes and Schwann cell precursors.Read moreRead less
Quantifying the adaptive immune response. The aim of this project is to develop mathematical models and computer software capable of predicting immune responses in infection and disease. The ability to predict immune responses should allow better vaccine design and better understanding of what causes the immune system to attack its own body, causing autoimmune disease, or fail to respond, causing immunodeficiency. The models and software will also be applicable to other areas of cell biology, ....Quantifying the adaptive immune response. The aim of this project is to develop mathematical models and computer software capable of predicting immune responses in infection and disease. The ability to predict immune responses should allow better vaccine design and better understanding of what causes the immune system to attack its own body, causing autoimmune disease, or fail to respond, causing immunodeficiency. The models and software will also be applicable to other areas of cell biology, such as describing growth and development. Thus, this project will lead to advances in understanding of fundamental biology, as well as potential improvements in treatments for a range of diseases.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
Does a novel class of small RNA molecules control self-incompatibility in solanaceous plants? Self-incompatibility is a simple and genetically defined cell recognition system that prevents inbreeding in many plant species. Flowers of self-incompatible plants can distinguish self pollen from foreign pollen, and allow only foreign pollen to fertilise their egg cells. This proposal will investigate the possibility that the part of the genetic self-incompatibility locus controlling recognition of ....Does a novel class of small RNA molecules control self-incompatibility in solanaceous plants? Self-incompatibility is a simple and genetically defined cell recognition system that prevents inbreeding in many plant species. Flowers of self-incompatible plants can distinguish self pollen from foreign pollen, and allow only foreign pollen to fertilise their egg cells. This proposal will investigate the possibility that the part of the genetic self-incompatibility locus controlling recognition of pollen is a novel type of gene that encodes a small RNA molecule but no protein. Knowledge gained by studying the self-incompatibility genes will help us to understand how plant cells recognise each other, and may allow us to manipulate seed (and hence crop) production.Read moreRead less
Subcellular recruitment of a RhoA ubiquitination complex by Rnd proteins. This study addresses a novel molecular mechanism through which members of the Rnd family of GTP-binding proteins regulate the morphology and migration of immature nerve cells of the developing nervous system. This study has broad implications for the understanding of cell migration during embryo development, as well as in health and disease.
Assessing the mechanisms and dynamics of myelination in the brain. This project is expected to refine our understanding of brain plasticity by revealing how myelin plasticity optimises brain function in response to experience. Using a multidisciplinary approach incorporating animal studies, mathematical modelling and computational neuroscience, the project seeks to redefine our understanding of myelin remodelling using an entirely new integrated cell-to-system approach. The expected outcome is f ....Assessing the mechanisms and dynamics of myelination in the brain. This project is expected to refine our understanding of brain plasticity by revealing how myelin plasticity optimises brain function in response to experience. Using a multidisciplinary approach incorporating animal studies, mathematical modelling and computational neuroscience, the project seeks to redefine our understanding of myelin remodelling using an entirely new integrated cell-to-system approach. The expected outcome is fundamental knowledge revealing how myelination is dynamically regulated by neural activity throughout life. This may transform current understanding of neuroplasticity that could aid in the future development of strategies to improve brain health.Read moreRead less
Electrical activity in early enteric neuron development. Intestinal movements and secretion are critical to the good health and nutrition of both humans and animals. These functions are regulated by a large nervous system contained within the intestinal wall, the enteric nervous system. This project will identify how enteric nerve cells develop and how their behaviour influences the development of other enteric nerve cells. This is will provide an important base for more applied research aime ....Electrical activity in early enteric neuron development. Intestinal movements and secretion are critical to the good health and nutrition of both humans and animals. These functions are regulated by a large nervous system contained within the intestinal wall, the enteric nervous system. This project will identify how enteric nerve cells develop and how their behaviour influences the development of other enteric nerve cells. This is will provide an important base for more applied research aimed at developing treatments for diseases like chronic constipation and irritable bowel syndrome. It will also contribute to the growing knowledge about how epigenetic factors can modify genetically programmed development within the nervous system.Read moreRead less