This is a multidisciplinary, multicenter, multisite Institutional NRSA proposal that is designed to provide training for dentists in the field of cell biology, molecular biology, biochemistry, developmental biology, pathobiology, and gene therapy. The program is prepared to take advantage of recent significant scientific advances on the part of faculty members. There are several scientific centers that promote a multi-disciplinary and interdisciplinary approach to biomedical research. The centers involved are: 1) the Center for Craniofacial Molecular Biology, 2) the Institute for Genetic Medicine, 3) the School of Dentistry, 4) the School of Medicine, and 5) the Department of Molecular Biology. They all interact to provide a method of mentoring students in the molecular biological arena. The proposal offers a wide spectrum of scientific training for students, which includes studying the mechanisms of cleft palate formation, the regulation of gene expression in facial muscles, prokaryotic virulence factors, analysis of gene expression in osteoblasts and osteoclasts, fidelity of DNA repair, physical and genetic mapping of human chromosomes, salivary gland development, molecular modeling through energy minimization, molecular dynamics of DNA-protein interactions, steroidal modification of gene expression during development and pathogenesis, epithelial mesenchymal interactions, oncogenes and carcinogenesis, and gene therapy. This is an ambitious proposal in which degree-seeking candidates will be admitted to the graduate school at the University of Southern California and complete core courses appropriate to the basic science requirements in one of the participating academic departments, select a research topic, and train under faculty members in a specific department to complete their degree. It is expected that the trainee applying for the doctoral degree will require five years of effort to complete the program and five years of support. Non-degree seeking candidates may also be selected, with training for a minimum of two years and a maximum of three years. Course work appropriate to the continuing training of postdoctoral fellows will be completed. The goal of the program is to develop trainees who are fully capable of pursuing an independent career in biomedical research after their training. The program also proposes to train predoctoral fellows as follows: three in the first year, six in the second year, nine in the third year, nine in the fourth year, and nine in the fifth year. The postdoctoral training will be as follows: three, six, nine, eleven, and eleven trainees, respectively. The program provides in excess of 20 different research areas in which the individual trainees can become involved. In the application, the program director gives an example of an individual training program in which a student selects the Department of Biology, Section of Molecular Biology, for training. There is a very comprehensive summary of the work that the student will take in the first, second, third, and fourth years of the program, which will include courses in advanced molecular biology, journal club, research units in laboratory rotations, molecular techniques, diagnostic and therapeutic applications, statistics for biologists, hormonal control of gene expression, etc. During the first year, students will have to maintain a B average and complete rotations in three laboratories. During the second year, students will initiate a thesis research area. In the third year and subsequent years, the trainees will have qualifying examinations. The program director provides a second example of a student who might select the Department of Biochemistry and Molecular Biology, and lists the courses that that individual would take. They include cell regulation and metabolism, membrane structure and function, chemical reaction mechanisms and biochemistry, enzyme kinetics and mechanisms, etc. Degree-seeking individuals in the third and fourth years will have limited course work, because of the intensive research laboratory experience that is necessary. After the students have a written examination, candidates will have an oral examination and a thesis defense. The oral examination is taken before a faculty guidance committee of five. Each student continues to meet at least yearly with a thesis advisory committee consisting of three to five members for evaluation of their progress. Although it would not be possible to give a detailed description of all of the nearly 10 program areas in which individuals can matriculate, the above two are excellent examples.