Clifford P. Brangwynne
The Nucleolus and Cell Growth Control
RNA/protein (RNP) bodies are a fascinating class of intracellular organelles involved in a wide range of fundamental biological processes. Unlike conventional organelles, which are bound by a lipid membrane, RNP bodies are non membrane bound structures that self-assemble from a soluble pool of RNA and protein components. The functional significance of the assembly of RNA and protein into these large-scale structures, consisting of thousands of individual molecules, remains poorly understood. Our studies in several model systems suggest that RNP bodies represent a liquid-like state of biological matter. This has shed light on our understanding of the biophysical control of their size, shape, and internal dynamics. Moreover, the liquid properties may underly their function as dynamic micro-reactors, concentrating RNA and protein reactants within a small cytoplasmic volume, but maintaining their high mobility to facilitate rapid RNA processing.
Our work involves developing a detailed understanding of the structure/function relationship of RNP bodies, and the consequences for fundamental biological processes. We are particularly interest in the nucleolus, a nuclear RNP body. Nucleoli play a critical biological role by providing large numbers of ribosomes necessary for sustained cell growth, explaining their importance in processes ranging from embryonic development to oncogenesis. However, we understand very little about nucleolar structure, and how this structure facilities its function as a micro-reactor for ribosome subunit assembly. How do the transiently interacting nucleolar components assemble into a coherent structure, with defined size and shape? Does the collective liquid behavior of nucleoli play a role in ribosome subunit processing and cell growth?
To address these questions, my lab is taking a novel biophysical approach using several model systems, including Xenopus frog oocytes, and the genetically tractable and optically transparent worm C.elegans. Our work in the frog system aims to build a detailed biophysical understanding of the nonequilibrium material properties of nucleoli, and how these properties facilitate ribosome subunit assembly. This complements our work in the worm where we are using 3D confocal imaging and custom image analysis algorithms to dissect the role of these biophysical properties in cell growth control within the context of a developing multicellular organism.