Interactions between ribosome biogenesis and regulatory networks of cell division in eukaryotic cells

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The long-term objective of our research program is to understand the molecular basis for the communication between two major cellular pathways: ribosome biogenesis and the cell cycle. Ribosomes are the cellular protein production machinery and as such very important as protein production is imperative for cell growth and a cell's ability to divide. Thus it is only logical that the synthesis of ribosomes is tightly linked to the regulation of cell division. Several connections between these two pathways have been identified in recent years, however, it is still unclear how mechanistically any communication is achieved between them. In my past work I have identified to proteins, Rrp14p and Nop15p, that appear to form an important control link between ribosome synthesis and very specific stages of the cell cycle. Their presence within cells is required not only for correct ribosome assembly, but also for correct position of the cell spindle, which physically segregates duplicated chromosomes, and correct timing of mother and daughter cell separation, respectively. How these proteins interact with the cell division machinery to achieve such control is still unknown. Using the budding yeast S.cerevisiae as our model system, we will characterize and study cell cycle machinery components that physically interact with Rrp14p and Nop15p, as well as regulatory mechanisms underlying their functions. This will provide a first insight into how two major cellular pathways communicate with each other in order to coordinate and regulate one another. Moreover, the project will set the stage for further investigations into the molecular mechanisms linking ribosome biogenesis and cell division, a topic that is becoming increasingly important in higher eukaryotes, where defects in ribosome biogenesis factors such as NIFK (hNOP15) were shown to result in malignant cell proliferation and disease development.