PI3K signalling and T lymphocyte development

T淋巴细胞，所谓的，因为他们在Thirdly发展，是一种类型的白色血细胞的免疫系统的功能至关重要。这些细胞的异常功能与免疫缺陷（例如AIDS）或自身免疫（例如I型糖尿病、类风湿性关节炎）相关。T淋巴细胞来源于造血干细胞，并在胸腺中完成其成熟，胸腺是一个位于心脏附近的器官，它已经进化到专门提供促进T细胞发育的环境。造血干细胞成熟为T淋巴细胞时所经历的发育阶段已经得到了相对良好的表征。这使得能够识别细胞必须通过的关键监管检查点，以便进一步发展。其中一个检查点被称为β选择。为了通过这个检查点，细胞必须产生特定的信号，引起基因表达的变化，并允许细胞分裂。β-选择信号也是细胞存活所必需的。我们已经确定了一些负责产生β选择信号的基因。这些被称为磷脂酰肌醇-3-激酶的基因是许多生物技术和制药公司正在积极研究的潜在药物靶点。我们的项目建议是进行实验，这将增加我们对磷脂酰肌醇-3-激酶信号传导如何受细胞表面受体调节以及如何与上游和下游过程相结合的理解。可以合理地断言，从早期T淋巴细胞分化研究中获得的一般原则可以在随后的发育阶段得到重申。因此，我们相信我们对早期T细胞发育的研究可能与健康和疾病中成熟T淋巴细胞活化的重要过程有关。

T lymphocytes, so-called because they develop in the Thymus, are a type of white blood cell crucial for the function of the immune system. Aberrant function of these cells is associated with immunodeficiency (e.g. AIDS) or autoimmunity (e.g. type I diabetes, rheumatioid arthritis). T lymphocytes are derived from blood stem cells and complete their maturation in the thymus, an organ located near the heart that has evolved specifically to provide an environment that promotes T cell development. The developmental stages haematopoietic stem cells pass through as they mature into T lymphocytes have been relatively well-characterised. This has allowed the identification of key regulatory checkpoints that cells must pass through in order to develop further. One of these checkpoints is called beta-selection. In order to pass through this checkpoint cells must generate specific signals which bring about changes in gene expression and allows the cells to divide. The beta-selection signal is also necessary for cells to survive. We have identified some of the genes which are responsible for generating the beta-selection signal. These genes which are called phosphatidylinositol-3- kinases are potential drug targets which are being actively investigated by many biotechnology and pharmaceutical companies. Our project proposal is to pursue experiments which will increase our understanding of how signalling by phosphatidylinositol-3- kinases is regulated by cell surface receptors and how this is integrated with upstream and downstream processes. It is reasonable to assert that general principles learned from study of early T lympchocyte differentiation may be reiterated at subsequent developmental stages. Thus, we believe our work on early T cell development may be relevant to processes important for the activation of mature T lymphocytes in health and disease.