SysCODE: Tooth Germ Design and Engineering (2 of 10)

SysCODE：牙胚设计与工程（10 中的 2）

• 批准号: 7502025
• 负责人: RICHARD L MAAS
• 金额: $ 56.61万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-28 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7502025
• 关键词: Address; Adult; Behavior; Biological; Cells; Clinical; Complex; Data; Dental; Dental Enamel; Development; Developmental Biology; Discipline; Effectiveness of Interventions; Embryo; Engineering; Epithelial; Epithelium; Extracellular Matrix; Gene Expression; Generations; Genetic; Genome; Genomics; Goals; In Vitro; Individual; Interdisciplinary Study; Jaw; Knowledge; Medicine; Mesenchymal; Mesenchyme; Molecular; Morphogenesis; Mus; Mutant Strains Mice; Natural regeneration; Odontogenesis; Organ; Pathway interactions; Population; Property; Proteins; Proteome; Proteomics; Regulator Genes; Science; Series; Signal Pathway; Signal Transduction; Solutions; Staging; Stem cells; Structure; Sum; System; Time; Tissue Engineering; Tissues; Tooth Germ; Tooth structure; base; computerized tools; design; engineering design; high throughput screening; in vivo; loss of function; mutant; Address; Adult; Behavior; Biological; Cells; Clinical; Complex; Data; Dental; Dental Enamel; Development; Developmental Biology; Discipline; Effectiveness of Interventions; Embryo; Engineering; Epithelial; Epithelium; Extracellular Matrix; Gene Expression; Generations; Genetic; Genome; Genomics; Goals; In Vitro; Individual; Interdisciplinary Study; Jaw; Knowledge; Medicine; Mesenchymal; Mesenchyme; Molecular; Morphogenesis; Mus; Mutant Strains Mice; Natural regeneration; Odontogenesis; Organ; Pathway interactions; Population; Property; Proteins; Proteome; Proteomics; Regulator Genes; Science; Series; Signal Pathway; Signal Transduction; Solutions; Staging; Stem cells; Structure; Sum; System; Time; Tissue Engineering; Tissues; Tooth Germ; Tooth structure; base; computerized tools; design; engineering design; high throughput screening; in vivo; loss of function; mutant

Recent advances in developmental biology, computational and genome science, and tissue engineering have made it possible to contemplate the regeneration of mammalian organs. The integration of knowledge from these disparate fields now enables the study of how individual components combine on a global scale to generate particular biological structures and functions. The application of such a systems-based approach to the problem of tooth engineering will make it possible to pursue rational rather than empiric strategies to fabricate a properly differentiated, enamel bearing tooth in vitro. Owing to current knowledge of the genetic pathways involved in odontogenesis and its clinical accessibility, the tooth represents an ideal target organ for the SysCODE Consortium. Like many mammalian organs, the tooth forms via a common developmental mechanism that involves the sequential, ordered exchange of signals between interacting epithelial and mesenchymal cell populations. We hypothesize that this complex, dynamic regulatory network can be resolved at the genetic and ultimately molecular level by the integration of different scientific disciplines and that this information can be used in the form of a molecular blueprint to design and build a tooth. To accomplish this goal, we propose three Specific Aims. In Aim 1, we will generate a dynamic time series of spatially resolved gene expression lists for the interacting epithelial and the mesenchymal cell populations that regulate early tooth morphogenesis. These analyses will be expanded to include select mouse mutants, limited proteomic data for abundant ECM proteins (w/ Project 5), and micromechanical design principles (w/ Project 6). In Aim 2, in conjunction with the SysCODE Computational Team, we will synthesize this information into a gene regulatory network (GRN), and with other data, into a molecular blueprint for early tooth development. This will involve the identification and ordering of canonical signaling pathways between dental epithelium and mesenchyme and analysis of transcriptional regulatory networks using new genomic and computational tools. Lastly, in Aim 3, we will employ tissue engineering platforms developed in Projects 7 and 9 in conjunction with the molecular blueprint and engineering design principles to direct tooth development in vitro. In sum, this Project has the potential to provide a paradigm for how interdisciplinary research can address a high impact problem whose solution can transform medicine.

发育生物学，计算和基因组科学以及组织工程的最新进展 使人们可以考虑哺乳动物器官的再生。知识的整合 现在，从这些不同的领域中，可以研究单个组件如何在全球范围内组合 生成特定的生物结构和功能。这种基于系统的应用 解决牙齿工程问题将使追求理性而不是经验的方法 制造适当分化的搪瓷轴承牙齿的策略。由于当前的了解 牙齿发生及其临床可及性涉及的遗传途径是理想的 Syscode联盟的目标器官。像许多哺乳动物器官一样，牙齿通过共同形成 涉及连续交互的顺序，有序交换的发展机制 上皮和间质细胞群体。我们假设这种复杂的动态调节 网络可以通过不同科学的整合在遗传和最终分子水平上解决 学科，这些信息可以以分子蓝图的形式使用，以设计和构建 齿。为了实现这一目标，我们提出了三个具体目标。在AIM 1中，我们将产生一个动态的时间 相互作用上皮和间质细胞的一系列空间分辨的基因表达列表 调节早期形态发生的种群。这些分析将扩展到包括选择 小鼠突变体，丰富的ECM蛋白质（W/ Project 5）的蛋白质组学数据有限 设计原则（W/项目6）。在AIM 2中，与SYSCODE计算团队一起，我们将 将此信息合并到基因调节网络（GRN）中，并与其他数据合成分子 早期牙齿发育的蓝图。这将涉及规范信号的识别和顺序 牙齿上皮和间质之间的途径以及转录调节网络的分析 使用新的基因组和计算工具。最后，在AIM 3中，我们将采用组织工程平台 与分子蓝图和工程设计原理一起在项目7和9中开发 在体外指导牙齿发育。总而言之，该项目有可能为如何提供范式 跨学科研究可以解决一个高影响问题，该问题可以改变医学。