INDIVIDUAL PREDOCTORAL DENTAL SCIENTIST FELLOWSHIP

个人博士前牙科科学家奖学金

• 批准号: 7056101
• 负责人: Eric Kern Harrington
• 金额: $ 2.76万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7056101
• 关键词: actins; annexins; cartilage; cell differentiation; chick embryo; chondrocytes; collagen; confocal scanning microscopy; gene induction /repression; immunocytochemistry; in situ hybridization; integrins; intermolecular interaction; neutralizing antibody; northern blottings; proteoglycan; transfection; western blottings

This application proposes a five year educational program at Baylor College of Dentistry, Texas A and M University System (BCD) for Mr. David Erik Kern. This program will combine Ph.D. studies in Biomedical Sciences with concurrent clinical training leading to a D.D.S. Mr. Kern's ultimate goal is a career in dental research and academic dentistry. His research interests are directed toward cartilage development and the genetic basis for chondrodysplasias, craniofacial abnormalities, and other genetic defects in human cartilage and bone development. A tentative research proposal is outlined, that will be modified as Erik begins the research component of the training. The research will address hypotheses concerning the cell-extracellular matrix interactions that are important for chondrocyte survival, proliferation and terminal differentiation. In previous work my group developed an organ culture model in which chondrocytes recapitulate normal development in their natural microenvironment. We have previously shown that sterna cultured with blocking integrin antibodies have decreased growth, survival, differentiation, and type X collagen secretion. This project builds on the previous work to further characterize the effects of cell-matrix interactions on collagen and other secreted protein synthesis and mRNA expression. Erik will specifically ask: How is type X collagen down regulated when cell-matrix interactions are blocked? Are other collagen (II, IX or XI) expression or synthesis affected by blocking cell-ECM interactions with integrin antibodies? Do other matrix proteins or molecules (cartilage matrix proteins, proteoglycans, or annexin V) change expression or synthesis in presence of blocking integrin antibodies? Do integrins themselves change expression or synthesis in the presence of blocking antibodies? Techniques will include maintaining whole cartilage in organ culture, immunoprecipitation, Western Blots, RNA extraction, Northern Blots, in situ hybridization, immunohistochemistry, and confocal microscopy.

该申请为David Erik Kern先生提议在德克萨斯州A和M大学系统（BCD）的贝勒牙科学院（BCD）进行五年的教育计划。 This program will combine Ph.D.与同时进行临床训练的生物医学科学研究导致了D.D.S.克恩先生的最终目标是牙科研究和学术牙科的职业。 他的研究兴趣是针对软骨发育和软骨发育，颅面异常和其他遗传缺陷的遗传基础的。 概述了一项暂定研究建议，随着Erik开始培训的研究部分，该建议将进行修改。 这项研究将解决有关细胞 - 纤细基质相互作用的假设，这些相互作用对于软骨细胞生存，增殖和末端分化很重要。 在先前的工作中，我的小组开发了一种器官培养模型，其中软骨细胞在其自然微环境中概括了正常发育。 我们先前已经表明，用阻断整联蛋白抗体培养的Sterna降低了生长，生存，分化和X型胶原蛋白分泌。 该项目建立在先前的工作基础上，以进一步表征细胞 - 矩阵相互作用对胶原蛋白和其他分泌蛋白质合成和mRNA表达的影响。 Erik会特别询问：当细胞 - 矩阵相互作用被阻止时，X型胶原蛋白如何向下调节？ 其他胶原蛋白（II，IX或XI）表达或合成是否受到与整合素抗体相互作用的影响？ 其他基质蛋白或分子（软骨基质蛋白，蛋白聚糖或膜联蛋白V）是否在存在封闭整合素抗体的情况下会改变表达或合成？ 整联蛋白本身是否在存在阻断抗体的情况下会改变表达或合成？ 技术将包括在器官培养中保持整个软骨，免疫沉淀，蛋白质印迹，RNA提取，北印迹，原位杂交，免疫组织化学和共聚焦显微镜。