Pappu, Harmon contribute to new findings on cell nucleolus structure

Washington University School of Engineering & Applied Science researchers were a part of team that has found new insights into the form and function of a cell’s nucleolus that could ultimately point toward new ways to treat disease.

Tyler Harmon

Rohit V. Pappu, the Edwin H. Murty Professor of Engineering, and Tyler Harmon, a doctoral student in Pappu’s lab, recently contributed their expertise in computational modeling and in fundamental understanding of the physics of intrinsically disordered proteins to a collaboration with the lab of Cliff Brangwynne, assistant professor in chemical and biological engineering at Princeton University. The collaboration uncovered the molecular basis of nucleolar structure. They showed that the protein and RNA components demix, similar to the way different vegetable oils do, to give rise to a layered structure for nucleoli. The results were recently published in the journal Cell.

Harmon and Pappu built on findings from Brangwynne’s lab to develop a computational model to show that the molecular architectures of key protein and RNA molecules encode the interactions that are sufficient to explain the spatially organized substructures of the nucleolus. The nucleolus is the hub where protein-making machines known as the ribosomes are made. The findings in the Cell paper suggest that the nucleolus is like a factory. It churns out RNA molecules that eventually leave the nucleolus and link up to form ribosomes.

Rohit Pappu

Beyond making ribosomes, the nucleolus has lately emerged as a hub for coordinating cellular growth, helping to regulate cell division and even setting the timing of a cell's self-destruction in reaction to stress or damage. Given this centrality, the nucleolus is also increasingly being recognized for roles in disease.

Further insight into the normal layout of nucleoli, as the new Cell study provides, will thus help in assessing the organelle as a promising therapeutic target for drugs in near future.

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Collaborative Research

WashU engineers Rohit Pappu and Tyler Harmon are co-authors of research published in the journal, Cell.

Princeton University: Clifford Brangwynne, Lian Zhu and Tiffany Richardson

St. Jude's Research Hospital: Diana Mitrea and Richard Kriwacki

Funding provided by: National Science Foundation, National Institutes of Health, National Cancer Institute, Helen Hay Whitney Foundation