This Program Project has made considerable scientific contributions to dental research in the past, and proposes to continue this tradition in the future. Since the original submission of our first Program Project Grant Application in 1968, we have made effort to promote fundamental research which evolve into science transfer technology for applications in clinical dentistry. This tradition continues. The present application has been designed to investigate the structure, function and molecular genetics of enamel genes and their products, and to transfer this knowledge towards the diagnosis of various types of amelogenesis imperfecta (AI), and the development of enamel bioceramics as a possible dental restorative material. The theme of our competing renewal program project grant is the assertion that enamel is a bioceramic, and that by understanding the structure, function and genetics of normal and abnormal enamel gene products a significant new technology will emerge enabling the fabrication of enamel in vitro. To achieve our goals, three inter- dependent subprojects are proposed to investigate (i) the structural biology of enamel proteins (e.g. amelogenins, tuftelins and enamel proteases), (ii) the function of enamel gene products in tissue-specific biomineralization, and (iii) the molecular genetics of amelogenesis imperfecta. In addition, these studies utilize the methodology of recombinant DNA technology, protein engineering, three-dimensional NMR, X-ray crystallography, computer-assisted molecular modeling, loss of function mutations (e.g., antisense inhibition strategies as well as immunoperturbation studies) using tooth organ culture and cell cultures (e.g. ameloblast cell cultures and transfection studies using odontoblast cell lines), and molecular genetics of human amelogenesis imperfecta including autosomal, X-linked and Y-linked inherited diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Program Projects (P01)
Project #
5P01DE002848-28
Application #
2872143
Study Section
Special Emphasis Panel (ZDE1-GH (25))
Project Start
1977-12-01
Project End
2001-01-14
Budget Start
1999-01-15
Budget End
2001-01-14
Support Year
28
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Southern California
Department
Other Basic Sciences
Type
Schools of Dentistry
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Fong, Hanson; White, Shane N; Paine, Michael L et al. (2003) Enamel structure properties controlled by engineered proteins in transgenic mice. J Bone Miner Res 18:2052-9
Moradian-Oldak, J (2001) Amelogenins: assembly, processing and control of crystal morphology. Matrix Biol 20:293-305
Wen, H B; Fincham, A G; Moradian-Oldak, J (2001) Progressive accretion of amelogenin molecules during nanospheres assembly revealed by atomic force microscopy. Matrix Biol 20:387-95
Paine, M L; White, S N; Luo, W et al. (2001) Regulated gene expression dictates enamel structure and tooth function. Matrix Biol 20:273-92
Wen, H B; Moradian-Oldak, J; Fincham, A G (2000) Dose-dependent modulation of octacalcium phosphate crystal habit by amelogenins. J Dent Res 79:1902-6
Wen, H B; Moradian-Oldak, J; Zhong, J P et al. (2000) Effects of amelogenin on the transforming surface microstructures of Bioglass in a calcifying solution. J Biomed Mater Res 52:762-73
Moradian-Oldak, J; Paine, M L; Lei, Y P et al. (2000) Self-assembly properties of recombinant engineered amelogenin proteins analyzed by dynamic light scattering and atomic force microscopy. J Struct Biol 131:27-37
Wen, H B; Moradian-Oldak, J; Leung, W et al. (1999) Microstructures of an amelogenin gel matrix. J Struct Biol 126:42-51
Fincham, A G; Moradian-Oldak, J; Simmer, J P (1999) The structural biology of the developing dental enamel matrix. J Struct Biol 126:270-99
Wen, H B; Moradian-Oldak, J; Fincham, A G (1999) Modulation of apatite crystal growth on Bioglass by recombinant amelogenin. Biomaterials 20:1717-25

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