Type XI collagen isoforms in skeletal biology

描述（由申请人提供）：候选人：朱莉娅牛津博士最近 获得了博伊西州立大学的终身职位。 她接受过蛋白质生物化学方面的培训， 她研究细胞外基质分子在发育中的作用， 疾病环境：博伊西州立大学对职业有承诺 发展科研队伍，培养学生 由教师谁是积极开展研究使用当前的技术。 该大学认识到生物信息学的重要性， 基因组学和蛋白质组学研究和培训，并大力支持这些， 最近的NIH BRIN拨款申请证明了这一点。研究项目：类型 Xi胶原蛋白是软骨胶原原纤维的组成部分。的 异型原纤维组装体与蛋白聚糖组分一起起作用， 软骨在发育过程中提供必要的生物力学特性， 生长和成人关节软骨。本研究旨在确定 Xi型胶原在细胞外基质中发挥作用的机制 组装和维持组织完整性。到目前为止，监管的效果 归因于Xi型胶原的原纤维生长已经用空间位阻解释， 通过胶原纤维表面上的氨基前肽阻碍。的 实际机制可能更复杂。拟议的努力是 设计用于检验I（Xi）胶原蛋白的同种型调节 纤维直径和氨基末端结构域参与分子 与细胞外基质的其他成分的相互作用， 基质组装和组织完整性。cc I（Xi）链可具有额外的 功能;特定同种型的表达可能表明 软骨（即永久性软骨或成为骨）。了解 X1型胶原的作用机制与调节基质有关 集会和组织。这些信息可以促进合理的 设计具有调节过量胶原的潜力的治疗剂 胶原纤维沉积和组织不良， 纤维化，主要器官如心脏，肾脏，肝脏，肺， 眼睛血管和皮肤调节细胞组装的能力 细胞外基质可能在组织领域具有重要意义， 工程也是。研究职业发展计划：直接职业 目标是建立一个生产性的研究实验室， 对细胞外基质领域的重大贡献 和疾病长期目标是整合研究和教学工作， 重点关注肌肉骨骼疾病和发育。强调 分子相互作用将利用蛋白质生物化学、组织培养和 分子生物学牛津博士将接受必要的培训，包括 负责任的研究行为，以支持研究工作和教学 学生在学术环境中使用这些方法。

DESCRIPTION (provided by applicant): Candidate: Dr. Julia Oxford has recently received an appointment to a tenure track position at Boise State University. She is trained in protein biochemistry and utilizes bioinformatic tools in her research on extracellular matrix molecules in development and disease. Environment: Boise State University has a commitment to the career development of faculty in scientific research and also the training of students by faculty who are actively carrying out research using current technologes. The University recognizes the importance of the inclusion of bioinformatics for genomics and proteomics research and training and strongly supports these, demonstrated by the recent NIH BRIN grant application. Research project: Type XI collagen is an integral component of the collagen fibrils of cartilage. The heterotypic fibrillar assembly functions with the proteoglycan component of cartilage to provide the necessary biomechanical properties during development, growth and as adult articular cartilage. This research aims to determine the mechanism by which type XI collagen plays a role in extracellular matrix assembly and maintenance of tissue integrity. To date, the effect of regulated fibril growth attributed to type XI collagen has been explained by steric hindrance by the amino propeptides on the surface of collagen fibrils. The actual mechanism is likely to be more complex. The proposed efforts are designed to test the hypothesis that isoforms of an I (XI) collagen modulate fibril diameter and that the amino terminal domain is involved in molecular interactions with other components of the extracellular matrix that mediate matrix assembly and tissue integrity. The cc I (XI) chain may have additional functions; the expression of a specific isoform may indicate the fate of cartilage (i.e. permanent cartilage or to become bone). Understanding the mechanism of type X1 collagen function has relevance to regulated matrix assembly and organization. This information could facilitate the rational design of therapeutic agents with the potential to modulate excessive collagen deposition and poor organization of collagen fibrils characteristic of fibrosis, a problem in major organs such as the heart, kidney, liver, lung, eye, blood vessels and skin. The ability to modulate the assembly of the extracellular matrix could be of great significance in the field of tissue engineering as well. Research career development plan: The immediate career goal is to establish a productive research laboratory that will make significant contribution to the field of extracellular matrix in development and disease. The long term goal is to integrate research and teaching efforts, with focus on musculoskeletal disease and development. The emphasis on molecular interactions will utilize protein biochemistry, tissue culture and molecular biology. Dr. Oxford will receive necessary training, including the responsible conduct of research, to support the research effort and to teach students these methods in an academic setting.