Role of unique ADP-ribosylating vacuolating Mycoplasma pneumoniae toxin i

独特的 ADP-核糖基化空泡肺炎支原体毒素 i 的作用

• 批准号: 8300811
• 负责人: JOEL Barry BASEMAN
• 金额: $ 203.36万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8300811
• 关键词: Acute; Address; Adult; Allergic; Allergic Disease; Antibodies; Asthma; Autopsy; Basic Science; Binding; Biological Assay; Biology; Biopsy; Cells; Child; Chronic; Clinical; Clinical Investigator; Clinical Research; Collaborations; Commit; Community Acquired Respiratory Distress Syndrome Toxin; Development; Diagnostic; Disease; Doctor of Philosophy; Essential Amino Acids; Evaluation; Fab Immunoglobulins; Fertilization; Functional disorder; Goals; Health; Human; Inflammation; Injury; Lead; Link; Lung; Lung diseases; Mediating; Mediator of activation protein; Modeling; Mus; Mycoplasma pneumoniae; Pathologic; Pathology; Patients; Pneumonia; Postdoctoral Fellow; Prevention; Procedures; Process; Proteins; Pulmonary Surfactant-Associated Protein A; Qualitative Evaluations; Reagent; Research; Research Project Grants; Resources; Role; Sampling; Structure; Techniques; Testing; Time; Toxin; Virulence; Virulence Factors; X ray diffraction analysis; X-Ray Diffraction; airway inflammation; clinical material; cofactor; follow-up; graduate student; injured airway; innovation; neutralizing monoclonal antibodies; novel diagnostics; novel therapeutics; rapid detection; success; therapeutic vaccine; three dimensional structure

DESCRIPTION (provided by applicant): The San Antonio Asthma and Allergic Diseases Cooperative Research Center (SA-AADCRC) represents a tightly focused, integrative and innovative effort to understand the role of Mycoplasma pneumoniae and its unique ADP-ribosylating and vacuolating toxin, designated Community Acquired Respiratory Distress Syndrome ToXin (CARDS TX) as important mediators of acute and chronic airway diseases, including new onset asthma and exacerbations, as well as persistent pulmonary dysfunction in children and adults. The basic science and clinical investigators who comprise the SA-AADCRC team share broad expertise and are highly collaborative. The SA-AADCRC's broad strategy of attack interlinks basic science and clinical research projects and cores. Project 1 uses the murine model and human materials to address fundamental questions on how CARDS TX induces asthma-like disease and exacerbates allergic pulmonary inflammation. Project 2 focuses on identifying CARDS TX ADP-ribosylating airway protein targets, delineating functionally important CARDS TX domains and essential amino acids that mediate CARDS TX binding to human surfactant protein A (SP-A) and airway cells, and generating antibody reagents that block/neutralize CARDS TX. Project 3 applies state-of-the-art biophysical techniques to uncover the structure and action of CARDS TX by using single crystal X-ray diffraction to determine CARDS TX three dimensional structure in the presence and absence of its cofactor NAD; neutralizing monoclonal antibody Fab fragments; and surfactant protein-A (SP-A). Clinical Core will collect human material from subjects with well controlled asthma, poorly controlled asthma and healthy controls and help in evaluation and follow-up of patient-related studies. Diagnostic Core will process clinical and experimental samples for diagnostic analysis by providing highly sensitive and specific diagnostic assays for rapid detection of M. pneumoniae CARDS TX. Pathology Core will provide necessary biopsy and necropsy procedures, lung pathology interpretation, histochemical and immunocytochemical evaluations, and qualitative and semiquantitative histopathologicai analyses. Administrative Core will oversee all SA-AADCRC-related activities and coordinate interactions and collaborations between projects and cores. Therefore, the SA-AADCRC represents a network of collaborators/colleagues who continuously ask fundamental and translational questions about asthma, airway-related pathologies, immunopathogenesis, and M. pneumoniae/CARDS TX biology and virulence mechanisms.

描述（申请人提供）：圣安东尼奥哮喘和过敏性疾病合作研究中心（SA-AADCRC）代表了一个紧密关注的，综合的和创新的努力，以了解肺炎支原体及其独特的ADP-核糖基化和空泡毒素，指定社区获得性呼吸窘迫综合征ToXin的作用。（BTX）作为急性和慢性气道疾病的重要介质，包括儿童和成人的新发哮喘和急性发作以及持续性肺功能障碍。组成SA-AADCRC团队的基础科学和临床研究人员共享广泛的专业知识，并高度合作。SA-AADCRC广泛的攻击策略将基础科学和临床研究项目和核心联系起来。项目1使用小鼠模型和人类材料来解决关于MTX如何诱导哮喘样疾病并加剧过敏性肺部炎症的基本问题。项目2的重点是确定ADP-TX核糖基化气道蛋白靶点，描绘功能重要的ADP-TX结构域和介导ADP-TX与人表面活性蛋白A（SP-A）和气道细胞结合的必需氨基酸，并产生阻断/中和ADP-TX的抗体试剂。项目3应用最先进的生物物理技术，通过使用单晶X射线衍射来确定在存在和不存在其辅因子NAD的情况下的BTX三维结构，来揭示BTX的结构和作用;中和单克隆抗体Fab片段;和表面活性蛋白-A（SP-A）。临床核心将从控制良好的哮喘受试者、控制不良的哮喘受试者和健康对照受试者中收集人体材料，并帮助评估和随访患者相关研究。诊断核心将通过提供用于快速检测M的高度敏感和特异性诊断检测来处理用于诊断分析的临床和实验样本。pneumoniae病理学中心将提供必要的活检和尸检程序、肺部病理学解释、组织化学和免疫细胞化学评价以及定性和半定量组织病理学分析。行政核心将监督所有SA-AADCRC相关活动，并协调项目和核心之间的互动和合作。因此，SA-AADCRC代表了一个合作者/同事网络，他们不断提出有关哮喘、气道相关病理学、免疫发病机制和M. pneumoniae/Pneumoniae TX生物学和毒力机制。