Testing the Mechanism of T lymphocyte selection in the thymus mediated by the zfp36 family of RNA binding proteins

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The immune system is made up of many different types of cell. One cell type called the T cell is a sensitive sensory system that can tell the difference between our own healthy cells and microorganisms or cancerous cells. Essential functions of the T cells are to coordinate the activity of other immune cells, such as cells that produce antibodies, and to form a memory of previous infections. This property is important for the function of vaccines. The absence of T cells leads to a serious medical problem called immunodeficiency. When T cells fail to discriminate properly healthy from unhealthy cells and become "autoreactive" life-threatening and chronic diseases can develop such as MS or type I diabetes. For these reasons understanding how T cells develop throughout the lifecourse is an important question. A significant body of work from many laboratories over several decades has identified cell surface receptors, mechanisms of signalling by those receptors and gene switches (called transcription factors) that control this process. Our research now identifies a new class of regulator of T cell development and selection that acts to control gene expression by controlling a process known as RNA decay. The goals of our research are to understand how this new class or regulator functions. We will study the process of thymocyte development using state of the art genetic and molecular biology approaches. We expect to understand the molecular mechanism by which this new class or regulator acts and to be able to interpret this within the context of the body of knowledge that already exists. The knowledge gained may enable new approaches to autoimmunity or immunodeficiency to be devised. This project will also provide an excellent training opportunity for an early stage researcher in basic molecular and cellular immunology.