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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：
Derk Joester
金额：
$ 63.65万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
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

来源：
https://reporter.nih.gov/project-details/10467066
关键词：
Address Affect Alleles Ameloblasts Amelogenesis Amelogenesis Imperfecta Atlases Benchmarking Biological Process Biology Biophysics Cell Separation Cell physiology Cells Chromosome Mapping Color Communities Complement Cre driver Defect Dental Enamel Dental caries Dentition Development Developmental Process Dimensions Disease Electrons Enamel Formation Flow Cytometry Fluorescence Gene Expression Gene Expression Profile Gene Expression Profiling Generations Genes Genetic Genetic Transcription Glean Health Heterogeneity Human Incisor Intervention Knock-in Length Life Maturation-Stage Ameloblast Measurement Mechanics Methods Microscopy Minerals Modeling Molecular Profiling Mus Mutant Strains Mice Nanostructures Nature Pathway interactions Peptide Hydrolases Peptides Phase Physiological Population Process Production Property Proteins Proteome Proteomics Psychological Impact Quality of life Reagent Regulation Reporter Reporter Genes Research Research Personnel Societies Specific qualifier value Structure System Techniques Tissues Tooth structure Translations Wild Type Mouse X-Ray Medical Imaging ameloblastin biophysical analysis biophysical properties cell behavior conditional knockout cost differential expression enamel matrix proteins gene function genetic approach in vivo innovation interest live cell imaging mass spectrometric imaging mechanical properties multimodality mutant next generation novel novel strategies rare condition self assembly single-cell RNA sequencing spatiotemporal tool transcriptome sequencing transcriptomics vibration

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