# Enamel atlas: systems-level amelogenesis tools at multiple scales

> **NIH NIH UH3** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $636,476

## Abstract

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.

## Key facts

- **NIH application ID:** 10467066
- **Project number:** 5UH3DE028872-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Derk Joester
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $636,476
- **Award type:** 5
- **Project period:** 2021-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10467066

## Citation

> US National Institutes of Health, RePORTER application 10467066, Enamel atlas: systems-level amelogenesis tools at multiple scales (5UH3DE028872-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10467066. Licensed CC0.

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