The role of ephrinB1 and ephrinB2 in controling gamma-delta T cell development

申请人是Eph/ephrin研究的先驱。自2000年以来，这项研究一直是他实验室的一个主要项目（资金来自其他来源）。以下描述的在未来5年内实施的短期目标是长期计划的一部分，该计划将在未来10年或更长时间内全面展开，其目标是阐明Ephs/ephins在免疫系统和心血管系统中的作用。三到六个博士学生将在未来10年内利用该方案作为一个工具接受培训。这个长期计划将是一个专门的NSERC计划。 在我们的免疫系统中，有两种类型的细胞，称为α/β T细胞和γ/δ T细胞，它们都是在胸腺中发育的，它们有共同的祖先。是什么决定了祖先成为α/β T细胞和γ/δ T细胞的决定还没有完全了解。我们发现有两种分子可以影响祖先的决策。在这个项目中，我们将研究这一发现的潜在机制。 我们有两个不相互排斥的假设：1）EFNB 1/B2与已知调节祖先决策的分子相互作用或调节分子; 2）EFNB 1/B2本身就是决策的调节剂。 该项目的具体目标如下： 1. 研究EFNB 1/B2是否与控制祖先决策的已知分子发生物理相互作用并影响其功能。 2. 评价EFNB 1/B2是否促进γ/δ T细胞的存活和生长。 3. 研究EFNB 1/B2如何触发祖先细胞内其他分子的级联反应，以进行决策。 意义这项研究将产生γ/δ T细胞命运决定的新知识。

The applicant is a pioneer in Eph/ephrin research. This research has been a major program (with funding from other sources) in his lab since 2000. The short-term objectives described hereafter to be carried out in the next 5 years are a part of a long-term program, which will be in full swing for the next 10 years and more, and the objectives of which are to elucidate the roles of Ephs/ephins in the immune system and cardiovascular system. Three to six Ph.D. students will be trained in the next 10 years using the program as a vehicle. This long-term program will be a dedicated NSERC program. In our immune system, there are two types of cells called alpha/beta T cells and gamma/delta T cells, and both of them are developed in the thymus and they have common ancestors. What determines the decision of the ancestors to become alpha/beta T cells and gamma/delta T cells is not fully understood. We found that two molecules called can influence the decision making of the ancestors. In this project, we will investigate the underlying mechanisms of this finding. We have two non-mutually exclusive hypotheses: 1) EFNB1/B2 interact with or modulate molecules known to regulate decision-making of the ancestors; 2) EFNB1/B2 are modulators of the decision making in their own right. The specific aims of this project are as follows: 1. To investigate whether EFNB1/B2 interact physically with and affect the function of known molecules that control the ancestor decision making. 2. To evaluate whetherEFNB1/B2 promote the survival and growth of gamma/delta T cells. 3. To investigate how EFNB1/B2 trigger a cascade of other molecules inside the ancestor cells for their decision making. Significance. This study will generate new knowledge in gamma/delta T cell fate determination.