The eukaryotic cell allocates extraordinary resources for the synthesis, processing, assembly, and regulation of its most complex ribonucleoprotein molecular machine, the ribosome. Under ideal growth conditions, yeast cells produce 2000 ribosomes each minute, each requiring the precise assembly of 4 RNAs and 79 protein components. The mechanistic details of how this remarkable process is coordinated and regulated have been the subject of longstanding interest.
Our lab is interested in understanding the dynamics of protein-RNA interactions during specific stages of eukaryotic ribosome biogenesis. In particular, we are focusing on the roles of multiple ATPases in the timing of ribosomal RNA remodeling events that define the internuclear maturation of pre-ribosomes and help modulate the regulatory interactions between ribosome biogenesis and the cell cycle machinery.
Rather than concentrating on a specific technique, we are using a combinatorial approach, bringing together the strengths of in vitro biochemical reconstitution, genetics, x-ray crystallography, cross-linking coupled to mass spectrometry, electron microscopy, and light microscopy to understand these events across multiple levels of resolution.