This research project addresses the biological functions of a unique domain within the cell nucleus - the nucleolus. The nucleolus has long been known as the seat of ribosome biosynthesis. However, a few years ago Dr. Pederson proposed in a semi-speculative essay (Pederson, T. 1998. The Plurifunctional Nucleolus. Nucleic Acids Research 26:3871-3876) that the nucleolus has other functions as well. This idea was greeted receptively and before long, increasing evidence began to be obtained as several groups turned their attention to the concept of a plurifunctional nucleolus.
Dr. Pederson's work on this concept has centered on the hypothesis that the nucleolus is a key station in the assembly of the signal recognition particle (SRP). His laboratory has identified both the RNA and certain protein components of the SRP in the nucleoli of cultured mammalian cells, as well as in the amplified nucleoli of frog oocytes. However, whether these components are actually in molecular contact with one another in the nucleolus has not been established, and this is one of the major objectives of the present project. Dr. Pederson has also speculated that the nucleolus may serve as a center for the coordinated co-regulation of SRP and ribosome synthesis (Pederson, T. and Politz, J.C. 2000. The Nucleolus and the Four Ribonucleoproteins of Translation. J. Cell Biology 148:1091-1095.) This hypothesis is also addressed in the present project.
In relation to the broader aspects of the field, it is to be borne in mind that numerous other functions have been suggested for the nucleolus recently, particularly relating to cell cycle progression. In addition, it has been claimed that some translation occurs in the nucleus, including in the nucleolus. The evidence for this is provocative but not definitive (Pederson, T. 2001. Is the Nucleus in Need of Translation? Trends in Cell Biology 11:395-397), and contradictory results have been obtained subsequently. However, neither of these additional putative functions are addressed directly in this project.
Broader Impacts:
Dr. Pederson is committed to the scientific education of both young students and the public at large. The project will serve as a platform for summer research training for undergraduate students drawn from a variety of colleges in the Worcester area, including members of underrepresented groups.