The purpose of the present application is to gain an in-depth understanding of the structure-function relationships of amelogenin, the most abundant protein in developing dental enamel. Previously we have demonstrated that amelogenin forms complex 3-dimensional suprastructures intimately linked to enamel crystal formation (Diekwisch et al. 1993, 1995, Diekwisch 1998). The crucial role of an intact amelogenin structure for healthy tooth enamel has been highlighted in recent genetic studies demonstrating that amelogenin single-point mutations cause enamel defects in affected individuals (Collier et al. 1997). In order to gain an understanding of how specific structural domains of the amelogenin molecule affect amelogenin function during enamel biomineralization we have designed a research plan to detect and model where, when, and how amelogenins form functionally important metastructures and how they substantially change their configuration under the influence of proteolytic enzymes, glycosylated substrates, and growing hydroxyapatite crystals. Hypothesis: The AMEL gene exerts its function related to enamel formation through specific motifs and domains that directly determine amelogenin supramolecular organization.
Specific Aims : 1. To define the temporospatial framework of amelogenins and enamel proteases in the developing enamel matrix. 2. To determine amelogenin and enamel protease function during enamel biomineralization in organ culture. 3. To determine the motifs and sites that govern amelogenin supramolecular organization in cell culture. 4. To determine the 3-dimensional structure of amelogenin using X-ray crystallography. These experiments will provide experimental data to understand the role of amelogenin proteins during enamel biomineralization, which will translate in an enhanced understanding of the clinical symptoms of Amelogenesis imperfecta as well as in the development of important clinical aids in the repair and regeneration of lost or diseased enamel.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
7R01DE013378-02
Application #
6541990
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Program Officer
Shum, Lillian
Project Start
2001-12-01
Project End
2006-07-31
Budget Start
2001-12-01
Budget End
2002-07-31
Support Year
2
Fiscal Year
2001
Total Cost
$227,071
Indirect Cost
Name
University of Illinois at Chicago
Department
Dentistry
Type
Schools of Dentistry
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
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