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

测试 RNA 结合蛋白 zfp36 家族介导的胸腺中 T 淋巴细胞选择机制

• 批准号: MR/N010434/1
• 负责人: Martin Turner
• 金额: $ 47.72万
• 依托单位: Babraham Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FN010434%2F1
• 关键词: Testing; Mechanism; lymphocyte; selection; thymus

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.

免疫系统由许多不同类型的细胞组成。一种称为T细胞的细胞类型是一种敏感的感觉系统，可以区分我们自己的健康细胞和微生物或癌细胞。T细胞的基本功能是协调其他免疫细胞的活动，如产生抗体的细胞，并形成对以前感染的记忆。这一特性对疫苗的功能至关重要。缺乏T细胞会导致严重的医学问题，称为免疫缺陷。当T细胞不能正确区分健康细胞和不健康细胞并成为“自身反应性”时，可能会发生危及生命的慢性疾病，如MS或I型糖尿病。因此，了解T细胞在整个生命过程中如何发育是一个重要的问题。几十年来，许多实验室的大量工作已经确定了细胞表面受体，这些受体的信号传导机制以及控制这一过程的基因开关（称为转录因子）。我们的研究现在确定了一类新的T细胞发育和选择调节因子，通过控制称为RNA衰变的过程来控制基因表达。我们研究的目标是了解这种新的类别或调节器如何发挥作用。我们将使用最先进的遗传学和分子生物学方法研究胸腺细胞发育的过程。我们希望了解这种新类别或调节剂作用的分子机制，并能够在现有知识体系的背景下解释这一点。所获得的知识可能使新的方法来设计自身免疫或免疫缺陷。该项目还将为基础分子和细胞免疫学的早期研究人员提供一个极好的培训机会。

项目成果

The timing of differentiation and potency of CD8 effector function is set by RNA binding proteins.

• DOI: 10.1038/s41467-022-29979-x
• 发表时间: 2022-04-27
• 期刊: Nature communications
• 影响因子: 16.6