Individual Predoctoral Scientist Fellowship

描述(由申请人提供)： 治疗炎症和骨质流失。炎症条件，如牙周病，会导致局部和全身免疫反应，这往往会导致有害后果，包括骨质流失。这些事件的主要介质是炎性细胞因子，如白介素17。到目前为止，只有IL-17受体(IL-17R)的一个亚基被鉴定出来，目前还不清楚是否有其他亚基也参与了IL-17R信号复合体的形成。由于典型的细胞因子受体至少由两个亚基组成，我们假设IL-17R也以多聚体的形式存在。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法。此外，我们建议描绘IL-17R的特定氨基酸，这些氨基酸对于与IL-17结合和介导特定信号至关重要。这将通过受体截断和定点突变来完成。阐明IL-17R的结构和结合结构域在牙周炎等炎症性疾病的治疗中具有潜在的治疗应用价值。

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.