MOLECULAR GENETICS AND GASTROINTESTINAL IMMUNOLOGY

分子遗传学和胃肠道免疫学

• 批准号: 3086428
• 负责人: VICTOR L FOX
• 金额: $ 6.66万
• 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/3086428
• 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.

以下计划将使福克斯博士准备好研究分子 免疫调节异常的机制 胃肠道。 该计划的第一阶段将侧重于获取基础知识 并发展高级工作所需的实验室技能 分子免疫学和分子遗传学。 这将发生在 Jon G. Seidman 博士的指导和直接监督， 哈佛医学院遗传学系。 拟议的 研究项目，“结构和功能分析 T细胞受体伽玛链基因座中的基因组V-J间隔，" 将作为学习必不可少的技术的工具 分子遗传学，同时剖析一个基本问题 免疫学。 该项目将从使用重叠粘粒开始 生成精确 V-J 距离的限制性内切酶图谱。 识别功能性转录产物并跟踪 这段基因组的最终命运将会随之而来。 初步的 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 受到哈佛大学研究生水平课程的称赞 大学，并通过出席和参加以下机构的研讨会 哈佛医学院、麻省理工学院、 马萨诸塞州总医院和丹纳法伯癌症中心 研究所。 第二阶段将在医学博士 W. Allan Walker 的指导下进行， HMS 儿科教授兼联合项目负责人 儿童医院的儿科胃肠病学和营养学 和麻省总医院。 从第一阶段收集的知识和经验 该程序将应用于胃肠道的研究 粘膜免疫和特定的分子遗传学 胃肠道疾病。 这将从表征 T-开始 克隆肠粘膜T细胞的细胞受体重排 来自麸质敏感肠病患者并扩展到 包括对 Kupffer 独特蛋白质编码基因的分析 细胞。