MOLECULAR GENETICS AND GASTROINTESTINAL IMMUNOLOGY

分子遗传学和胃肠道免疫学

• 批准号: 3086427
• 负责人: VICTOR L FOX
• 金额: $ 6.67万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3086427
• 关键词: Kupffer's cell; T cell receptor; T lymphocyte; autoimmune disorder; biopsy; celiac disease; child (0-11); clone cells; endonuclease; gastrointestinal disorder; gastrointestinal system; gene rearrangement; genetic library; genetic mapping; genetic transcription; human subject; immunogenetics; intestinal mucosa; lymphocyte; medical education; molecular cloning; molecular genetics; monoclonal antibody; plasmids; protein biosynthesis; protein structure; tissue /cell culture

The following plan will prepare Dr. Fox to investigate molecular mechanisms involved in immunoregulatory abnormalities of the gastrointestinal tract. Phase I of this plan will focus on acquiring fundamental knowledge and developing laboratory skills required for advanced work in molecular immunology and molecular genetics. This will occur under the guidance and direct supervision of Jon G. Seidman, Ph.D., Department of Genetics, Harvard Medical School. The proposed research project, "Structural and Functional Analysis of the Genomic V-J Interval in the T-cell Receptor Gamma Chain Locus," will serve as a vehicle for learning techniques essential to molecular genetics while dissecting a fundamental problem of immunology. The project will begin by using overlapping cosmids to generate a restriction enzyme map of the exact V-J distance. Identifying functional transcription products and tracking the ultimate fate of this piece of the genome will follow. Preliminary cell culture work with intestinal lymphocytes will prepare for the transition to Phase II. The Phase I research experience will be complimented by graduate level courses conducted at Harvard University, and by attending and participating in seminars at Harvard Medical School, Massachusetts Institute of Technology, Massachusetts General Hospital, and The Dana-Farber Cancer Institute. Phase II will ensue under the guidance of W. Allan Walker, M.D., Professor of Pediatrics, HMS, and Chief of the Combined Program of Pediatric Gastroenterology and Nutrition at The Children's Hospital and MGH. The knowledge and experience gathered from Phase I of this program will be applied to the study of gastrointestinal mucosal immunity and the molecular genetics of specific gastrointestinal disorders. This will begin by characterizing T- cell receptor rearrangements of cloned intestinal mucosal T cells from patients with gluten-sensitive enteropathy and expand to include analysis of genes encoding proteins unique to Kupffer cells.

下面的计划将为福克斯博士研究分子 细胞免疫调节异常机制的研究进展 胃肠道。 该计划的第一阶段将侧重于获取基础知识 和开发高级工作所需的实验室技能 分子免疫学和分子遗传学。这将在以下情况下发生 乔恩·G·塞德曼博士的指导和直接监督 哈佛医学院遗传学系。建议数 研究项目《汽车的结构和功能分析》 T细胞受体γ链基因座的基因组V-J间期 将作为学习技术的载体，这些技术 分子遗传学在剖析人的一个基本问题时 免疫学。该项目将通过使用重叠的宇宙来开始 以生成准确的V-J距离的限制酶图谱。 鉴定功能转录产物并跟踪 这段基因组的最终命运将随之而来。初步 肠道淋巴细胞的细胞培养工作将为 过渡到第二阶段。第一阶段的研究经验将是 在哈佛大学开设的研究生级别的课程 大学，并通过参加和参加研讨会 哈佛医学院，麻省理工学院， 马萨诸塞州总医院和达纳-法伯癌症 研究所。 第二阶段将在W.Allan Walker医学博士的指导下进行， 英国卫生与公众服务部儿科学教授兼综合项目负责人 儿童医院的儿童胃肠病和营养学 和MGH。从第一阶段收集的知识和经验 本课题将应用于胃肠疾病的研究。 粘膜免疫与特异性肺炎的分子遗传学 胃肠道疾病。首先，我们将描述T- 克隆的肠粘膜T细胞的细胞受体重排 从面筋敏感型肠病患者中分离出来并扩展到 包括对库普弗独有蛋白质编码基因的分析 细胞。