EnamelBase: About Us
What is the EnamelBase?
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 - amelogenesis - remains poorly understood.(1) Among the factors that have delayed progress 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.(2-4) 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.
Taking full advantage of these recent technical advances, we have created an integrated, multi-modal set of tools and reference materials. Specifically, we have generated stage specific Cre drivers, reporters, conditional knockout and knock-in models of key structural and proteolytic proteins that constitute the enamel matrix. We are currently working 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 are being 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.
References
- Ophir D Klein, Olivier Duverger, Wendy Shaw, Rodrigo S Lacruz, Derk Joester, Janet Moradian-Oldak, Megan K Pugach, J Timothy Wright, Sarah E Millar, Ashok B Kulkarni, John D Bartlett, Thomas GH Diekwisch, Pamela DenBesten & James P Simmer, “Meeting report: a hard look at the state of enamel research”, Int J Oral Sci 2017, 9, e3 .
- Lyle M Gordon, Michael J. Cohen, Keith W MacRenaris, Jill D Pasteris, Takele Seda, & Derk Joester, “Amorphous intergranular phases control the properties of rodent tooth enamel”, Science 2015, 347, 746-750 .
- Lyle M Gordon & Derk Joester, “Mapping residual organics and carbonate at grain boundaries and in the amorphous interphase in mouse incisor enamel”, Front Physiol 2015, 6 .
- K. A. DeRocher, Paul J M Smeets, Berit H Goodge, Michael J Zachman, Prasanna V Balachandran, Linus Stegbauer, Michael J Cohen, Lyle M Gordon, James M Rondinelli, Lena F Kourkoutis & Derk Joester, “Chemical gradients in human enamel crystallites”, Nature 2020, 583, 66-71 .