I will seek to define the structure and function of the NOR 90K protein. This is a newly discovered component of the nucleolus and is present within the nucleolus-organizing-regions of metaphase chromosomes. I will use standard cloning methods to derive a full length cDNA for the gene that encodes this protein. That effort will provide information about the primary and possibly the secondary structure of this protein. It will also provide a useful probe for studies of the species and tissue distribution of the NOR 90K gene and the circumstances of its expression. In a separate approach, I will isolate the NOR 90K protein biochemically and examine its ability to bind to specific base sequence within DNA. I will also localize this protein at the level of resolution of the electron microscope. These studies should provide sufficient information so that hypotheses about the function of this protein can be developed and tested. In phase 2 of this program, I will turn my attention to more clinically related problems and seek to understand why the NOR 90K protein acts as an autoantigen in scleroderma. Through a rigorous series of basic course work, the research program outlined in this proposal, and the constant supervision of my mentors, I feel confident that this program will provide a sound foundation for a career in academic rheumatology.
| Kipnis, R J; Craft, J; Hardin, J A (1990) The analysis of antinuclear and antinucleolar autoantibodies of scleroderma by radioimmunoprecipitation assays. Arthritis Rheum 33:1431-7 |
