MOLECULAR GENETICS AND GASTROINTESTINAL IMMUNOLOGY

以下计划将为福克斯博士研究分子 参与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得基本知识 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的指导和直接监督。Seidman博士， 哈佛医学院遗传学系。 拟议 研究项目，“结构和功能分析的 T细胞受体γ链基因座中的基因组V-J间隔，” 将作为学习必要技术的工具， 分子遗传学的同时， 免疫学 该项目将开始使用重叠cosmetics 以生成精确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随之而来。 初步 肠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课程中， 大学，并出席和参加在 哈佛医学院，马萨诸塞州理工学院， 马萨诸塞州总医院和达纳法伯癌症中心 院 第二阶段将在W。艾伦步行者，医学博士， 儿科学教授，HMS，和联合项目主任， 儿童医院的小儿胃肠病学和营养 MGH的。 从第一阶段收集的知识和经验， 本程序将应用于胃肠动力学的研究， 粘膜免疫和特异性的分子遗传学 胃肠道疾病 这将开始通过表征T- 克隆的肠粘膜T细胞的细胞受体重排 从谷蛋白敏感性肠病患者，并扩大到 包括分析编码Kupffer特有蛋白质基因 细胞

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.