BIOLOGY AND BIOMETRICS OF ENAMEL CRYSTAL GROWTH

牙釉质晶体生长的生物学和生物特征学

• 批准号: 6523884
• 负责人: Tom Diekwisch
• 金额: $ 25.91万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6523884
• 关键词: X ray crystallography; amelogenin; biomimetics; dental development; electron microscopy; endopeptidases; enzyme activity; extracellular matrix; gene deletion mutation; histogenesis; hydroxyapatites; immunocytochemistry; in situ hybridization; laboratory mouse; normal ossification; organ culture; point mutation; polymerase chain reaction; protein structure function; site directed mutagenesis; tissue /cell culture; tooth enamel

DESCRIPTION (provided by applicant): The purpose of the present application is to gain an in-depth understanding of the structure-function relationships of amelogenin, the most abundant protein in developing dental enamel. Previously we have demonstrated that amelogenin forms complex 3-dimensional suprastructures intimately linked to enamel crystal formation (Diekwisch et al. 1993, 1995, Diekwisch 1998). The crucial role of an intact amelogenin structure for healthy tooth enamel has been highlighted in recent genetic studies demonstrating that amelogenin single-point mutations cause enamel defects in affected individuals (Collier et al. 1997). In order to gain an understanding of how specific structural domains of the amelogenin molecule affect amelogenin function during enamel biomineralization we have designed a research plan to detect and model where, when, and how amelogenins form functionally important metastructures and how they substantially change their configuration under the influence of proteolytic enzymes, glycosylated substrates, and growing hydroxyapatite crystals. Hypothesis: The AMEL gene exerts its function related to enamel formation through specific motifs and domains that directly determine amelogenin supramolecular organization. Specific Aims: 1. To define the temporospatial framework of amelogenins and enamel proteases in the developing enamel matrix. 2. To determine amelogenin and enamel protease function during enamel biomineralization in organ culture. 3. To determine the motifs and sites that govern amelogenin supramolecular organization in cell culture. 4. To determine the 3-dimensional structure of amelogenin using X-ray crystallography. These experiments will provide experimental data to understand the role of amelogenin proteins during enamel biomineralization, which will translate in an enhanced understanding of the clinical symptoms of Amelogenesis imperfecta as well as in the development of important clinical aids in the repair and regeneration of lost or diseased enamel.

描述（由申请人提供）：本申请的目的是深入了解