Intellectual merit. This research project concerns a specialized architectural domain within the cell nucleus, called the nucleolus. It has long been known that the nucleolus contains genes that produce the RNA component of cellular particles called ribosomes. The RNA made by these genes combines with certain proteins in the nucleolus and the resulting ribosome particles then move to the cytoplasm of the cell where they serve as factories for the biosynthesis of proteins. In research previously supported by NSF, the principal investigator of this project discovered that the nucleolus has additional functions beyond its role in the production of ribosomes. The present project will investigate the nucleolar presence of non-ribosome particles that contain proteins involved in cell growth and division. Related studies will track the dynamic movements of these non-ribosome particles between the nucleolus and the other regions of the nucleus. In a third line of investigation, the presence in nucleoli of special RNA molecules known as microRNAs will be pursued in an effort to understand the functional significance of their nucleolar localization.

Broader impacts. This research will be conducted in such a way as to optimize broader impacts. It will involve advanced training of a post-doctoral fellow and a number of rotation students. In addition to standard dissemination of the findings both in published articles and at scientific conferences, the principal investigator will incorporate this axis of research into his broader writing and lecturing on the cell biology of the nucleus. The principal investigator also makes use of his position as Associate Editor of the journal Nucleus to publish commentaries on the nucleolus and the nucleus, as he does also from time to time in the widely read FASEB Journal, of which he is an editor. It is believed that the present research project has the potential to illuminate a key conundrum about the cell nucleus, namely how such a dynamic organelle as regards the complexity of its molecular interactions nonetheless functions in such an integrated way, and in very high spatial constraints. Thus, this research may contribute to the broad intellectual structure of the cell biology field.

Project Report

This research project was designed to reveal new functions of a part of the cell called the "nucleolus". This is a structure that is located inside the cell's nucleus together with the chromosomes. It had once been thought that the nucleolus has a single function, which is to build the molecular machines the cell uses to synthesize proteins. (These machines are called "ribosomes"). In the recently completed project, we found that the nucleolus has two additional features. The first is that it functions in regulating cell growth and does so independently of its role in producing ribosomes. The second feature is that the nucleolus harbors a certain family of genetic elements called RNA, in particular ones called messenger RNA and microRNA. This latter finding was completely unanticipated and suggests that the nucleolus is directing genetic readout in the cell. Because these findings from the project are so novel, the Principal Investigator has made a strong effort to disseminate them beyond standard publication for narrow groups of specialists. These efforts have included presentations to broad audiences of biologists at venues both in the U.S. and abroad. In additon, the Principal Investigator prepared a special article for publication in a journal read by many cancer researchers, so that the newly discovered role of the nucleolus in cell growth control would be known to them. In additon, a news article recently published in Science magazine drew attention to the newly discovered features of the nucleolus. The investment made by the U.S. National Science Foundation in this and related research on the nucleolus has thus brought strong dividends, as well as pointing the way to promising applications.

Agency
National Science Foundation (NSF)
Institute
Division of Molecular and Cellular Biosciences (MCB)
Application #
1051398
Program Officer
Gregory W. Warr
Project Start
Project End
Budget Start
2011-04-01
Budget End
2014-03-31
Support Year
Fiscal Year
2010
Total Cost
$801,203
Indirect Cost
Name
University of Massachusetts Medical School
Department
Type
DUNS #
City
Worcester
State
MA
Country
United States
Zip Code
01655