3/29/2012 8:00:00 AM
RNA helicases in RNA/protein body assembly and function: a multi-scale approach
The central innovation is our multi-scale approach combining single molecule imaging, soft matter biophysics, and developmental cell biology. Our common goal is to understand how the molecular activities of RNA helicases play a role in the assembly and biophysical features of nuclear and cytoplasmic RNA/protein (RNP) bodies, and how these structures contribute to the control of diverse RNA regulatory gene expression programs of a developing tissue. Our multi-scale effort seeks to connect the angstrom level molecular interactions to tissue level phenotype, providing insights into the mechanisms underlying dynamic RNP-mediated RNA regulation.
The synergy of our team arises from our unique combination of expertise that bridges structural length scales from single molecules (Myong, University of Illinois), to subcellular organization (Brangwynne, Princeton) and ultimately tissue formation (Eckmann, MPI Dresden, Germany). To develop a fundamental understanding of the nature and functional consequences of large scale RNP assemblies, we employ a broad range of interdisciplinary experimental techniques, and exploit the benefits of two complementary developmental model organisms, Caenorhabditis elegans and Xenopus laevis. Specifically, Eckmanns expertise in RNA/protein interactions and developmental gene expression enables Brangwynne to assign the contribution of individual helicases to mesoscale biophysical properties of RNP bodies, and Myong to conduct single molecule studies on physiologically relevant helicase/RNA partners and developmentally important cofactors. Myongs single molecule expertise offers Eckmann and Brangwynne an extended dimension through which systems biology parameters and biophysical properties of RNP bodies are tested, assayed, and interpreted at the level of single molecule dynamics of individual helicases. Furthermore, Brangwynnes ability to interrogate the biophysical properties of large-scale RNA helicase assemblies opens up a new avenue for Myong and Eckmann to investigate the consequences of RNA-protein interactions for the mesoscale properties of RNP bodies. The tightly inter-dependent nature of our collaboration entails long-term visits to each others laboratory, generation of shared reagents, exchange of samples, and education of each team in novel experimental designs. The resulting quantitative, multi-scale physical picture of RNP bodies would be impossible to obtain without an extremely close collaboration between the three members of our team.
Research Grant Awardees 2012 (Young Investigator and Program Grants)
- 8 Young Investigator Grants and 25 Program Grants were selected from a total of almost 800 original letters of intent and 96 subsequently invited full applications.