Enamel atlas: systems-level amelogenesis tools at multiple scales

牙釉质图谱:多尺度的系统级釉质生成工具

基本信息

  • 批准号:
    10467066
  • 负责人:
  • 金额:
    $ 63.65万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-08-01 至 2024-07-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT Enamel defects, whether congenital, acquired, or environmental in origin, are associated with a significant cost to society and also have profound psychological impacts. Despite significant progress over the last decade, the developmental process that gives rise to enamel, known as amelogenesis, remains poorly understood. We have identified at least two factors that have delayed progress, and which we propose to address in this application. One is that existing mouse reagents, which provide the primary model for understanding genetic regulation of amelogenesis, have deficiencies that hinder dissecting the mechanisms in vivo. Another challenge is that new information regarding the nanostructure and phase composition of enamel have begun to emerge that prior models did not take into account. The ability to access powerful new genetic approaches, “omics” techniques and materials characterization methods therefore creates unprecedented opportunities to generate sophisticated new tools that will help push amelogenesis research to the next level. We propose to take full advantage of these recent technical advances and of the complementary expertise of our team to create an integrated, multi-modal set of tools and reference materials. Specifically, we will generate innovative mouse reagents, including amelogenesis-stage specific Cre drivers, reporters and conditional knockout and knock-in models of key structural and proteolytic players that constitute the enamel matrix, which will enable a workflow to profile transcription (using RNA sequencing) and translation (using proteomics) at specific developmental stages, and even on a single cell basis (using single-cell RNA sequencing). Tissue and cell-level molecular profiling will be complemented by an in-depth characterization of the structure, composition, and mechanical properties of forming and mature enamel at overlapping length scales. By mapping gene expression, specifying local proteomes, and quantitatively assessing impact of the perturbations at each of these levels on the materials properties of enamel, we will create a platform that will empower amelogenesis researchers, help delineate mechanisms of disease, and lay the groundwork to enable the development of new approaches of intervention.
摘要

项目成果

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Derk Joester其他文献

Derk Joester的其他文献

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{{ truncateString('Derk Joester', 18)}}的其他基金

Enamel atlas: systems-level amelogenesis tools at multiple scales
牙釉质图谱:多尺度的系统级釉质生成工具
  • 批准号:
    10416107
  • 财政年份:
    2021
  • 资助金额:
    $ 63.65万
  • 项目类别:
Enamel atlas: systems-level amelogenesis tools at multiple scales
牙釉质图谱:多尺度的系统级釉质生成工具
  • 批准号:
    10670353
  • 财政年份:
    2021
  • 资助金额:
    $ 63.65万
  • 项目类别:
Nanoscale structure and phase composition of sound and carious enamel
完好牙釉质和龋牙釉质的纳米结构和相组成
  • 批准号:
    8954557
  • 财政年份:
    2015
  • 资助金额:
    $ 63.65万
  • 项目类别:
SYNTHESIS AND AGGREGATION OF CALCIUM CARBONATE IN PHOSPHOLIPID VESICLES
磷脂囊泡中碳酸钙的合成和聚集
  • 批准号:
    8361302
  • 财政年份:
    2011
  • 资助金额:
    $ 63.65万
  • 项目类别:

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