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

申请者是Eph/EPhin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)。下文所述的短期目标将在未来5年内实施，这是一个长期计划的一部分，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。在接下来的10年里，将有3到6名博士生以该项目为载体接受培训。这一长期计划将是一项专门的NSERC计划。 在我们的免疫系统中，有两种类型的细胞，称为α/βT细胞和伽马/德尔塔T细胞，这两种细胞都是在胸腺发育的，它们有共同的祖先。是什么决定了祖先决定成为阿尔法/贝塔T细胞和伽马/德尔塔T细胞，目前还不完全清楚。我们发现有两个分子可以影响祖先的决策。在这个项目中，我们将调查这一发现的潜在机制。 我们有两个不相互排斥的假设：1)EFNB1/B2与已知调节祖先决策的分子相互作用或调节；2)EFNB1/B2本身就是决策的调节器。 该项目的具体目标如下： 1.研究EFNB1/B2是否与控制祖先决策的已知分子相互作用并影响其功能。 2.探讨EFNB1/B2是否能促进γ/Delta T细胞的存活和生长。 3.研究EFNB1/B2如何触发祖先细胞内其他分子的级联反应，以便做出决策。 意义重大。这项研究将在确定伽马/德尔塔T细胞命运方面产生新的知识。

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.