Individual Predoctoral Scientist Fellowship

描述（由申请人提供）： 治疗炎症和骨质流失。 炎症性疾病，如牙周病，导致局部和全身免疫反应，往往导致有害的后果，包括骨质流失。 这些事件的主要介质是炎性细胞因子，如白细胞介素（IL）-17。 迄今为止，仅鉴定了IL-17受体（IL-17 R）的一个亚基，并且尚不清楚其他亚基是否也参与IL-17 R信号传导复合物。 由于典型的细胞因子受体由至少两个亚基组成，我们假设IL-17 R也作为多聚体存在。 为了确定亚基是否形成同源二聚体，将使用三种方法，包括嵌合受体方法、荧光共振能量转移和生物化学交联。 此外，我们建议描绘特定的氨基酸的IL-17 R的结合IL-17和介导的特定信号是至关重要的。 这将通过受体截短和定点诱变来完成。 IL-17 R构型和结合结构域的阐明在治疗炎性疾病如牙周炎中具有潜在的治疗应用。

DESCRIPTION (provided by applicant): The treatment of inflammation and bone loss. Inflammatory conditions such as periodontal disease result in both local and systemic immune responses that often lead to deleterious consequences, including bone loss. The primary mediators of these events are inflammatory cytokines, such as interleukin (IL)-17. To date, only one subunit of the IL-17 receptor (IL-17R) has been identified, and it is not clear whether other subunit also participate in the IL-17R signaling complex. Since typical cytokine receptors consist of at least two subunits, we hypothesis that the IL-17R also exists as a multimer. To determine whether the subunits form a homodimer, three approaches will be used, including a chimeric receptor approach, flurescence resonance energy transfer, and biochemical cross-linking. In addition, we propose to delineate specific amino acids of the IL-17R that are critical for binding to IL-17 and mediating a specific signal. This will be done by receptor truncations and site directed mutagenesis. Elucidation of the IL-17R configuration and binding domains has potential therapeutic applications in the treatment of inflammatory diseases such as periodontitis.