Abstract:
In every human cell, 6 ft of DNA and thousands of RNAs and proteins are compacted to fit inside a tiny nucleus. Yet, these molecules are not randomly arranged in the nucleus. Instead, proteins, DNAs, and RNAs are organized in specialized compartments like nuclear bodies, which are thought to play key roles in RNA processing. The nucleolus is the most prominent nuclear body in eukaryotes, coordinating a complex assembly line where thousands of ribosomal DNA genes, RNAs, and proteins work together to transcribe, process, fold, and export functional ribosomal subunits. Yet, despite being first observed almost two centuries ago, we do not fully understand how nuclear bodies function. This is largely because we have lacked tools to (i) measure their components, (ii) dissect how they form, and (iii) probe their functions. To address this, I have been developing a unique genomic toolkit to map, measure, and perturb nuclear organization and function. In my Ph.D., I developed a novel genomic approach, SPRITE, to map RNA and DNA organization throughout the cell, revealing how the genome is arranged around various nuclear bodies. More recently, in my postdoctoral work, I have focused on the nucleolus as a model for understanding nuclear body functions in RNA processing. Using sequencing in parallel with imaging, we found that ribosomal RNA (rRNA) processing steps are spatially segregated in the nucleolus, with sequential rRNA maturation required for its outward movement through nucleolar phases. Furthermore, by generating synthetic de novo nucleoli through an engineered rDNA plasmid system in cells, we show that defects in RNA processing can alter the ordering of nucleolar phases, resulting in inside-out nucleoli and preventing rRNA outflux. These findings demonstrate how rRNA is both a scaffold and substrate for the nucleolus, with rRNA acting as a programmable blueprint for the multiphase architecture that facilitates assembly of an essential molecular machine.
Zoom Link here: https://upenn.zoom.us/j/99148757177?pwd=Gb7s4LgOFFUT7dhBpm3NauQegy6Tsh.1
Bio:
Sofia Quinodoz is working to study nuclear organization and its role regulating cellular functions as a HHMI Hanna H. Gray Fellow at Princeton University in Cliff Brangwynne’s Laboratory. As an undergraduate, Sofia studied Molecular Biology at Princeton University with a focus in Quantitative and Computational Biology. During her Ph.D. at Caltech in Mitch Guttman’s Lab, she developed a novel genomic tool, SPRITE, to measure RNA and DNA organization in the nucleus. She was awarded the Fred Hutch Weintraub Award, HHMI Gilliam Fellowship, and NSF GRFP Fellowship.