Friday, May 9, 2025
5/9/2025
Organization of Syncytial Cells - Project Summary Syncytial cells have multiple nuclei in a shared cytoplasm and are common in the biosphere. These cells are found in fungal pathogens and symbionts, during embryogenesis of plants and animals, and in bone, blood, placenta, muscle, and tumor cells of humans. Nuclei sharing a syncytium can differ in genotype, or in gene expression profile, so that these single cells can approach the functional complexity of a multicellular tissue, especially when they grow to a large and complex shape. What functions emerge with this form of cell organization that are distinct from a multicellular tissue? How can a single cell be spatially organized to support different nuclear identities and functions in a common cytoplasm? My lab’s long-term goal is to discover the functions of syncytia and to uncover fundamental cell biology that emerges from this unique cell organization. We have made foundational discoveries in understanding how the nuclear division cycle is spatially compartmentalized in syncytia. We deciphered how cyclin mRNAs drive the formation of biomolecular condensates in the vicinity of nuclei and defined fundamental rules for how cells control the location, size and composition of condensates. The nuclear division cycle is also in part controlled locally by cortical septin cytoskeleton assemblies that act as signaling scaffolds, controlling the concentrations of cell cycle regulators in their vicinity. Our recent focus has been on how septins assemble at specific locations in cells. We discovered that septins preferentially assemble on micron-scale curved membranes, leading them to enrich at specific locations where cells change shape. The proposed future research in a model filamentous fungus addresses gaps in understanding how condensates and septins create functional zones for cell cycle signaling within syncytial cells but also extends to new areas for the lab. In theme 1, we will examine how condensates regulate translation of cyclin proteins in time and space, dissecting how the material state and composition of condensates controls protein synthesis. In theme 2, we will determine how different types of septin assemblies recruit sets of effector proteins to locally control signaling to the cell cycle. This is critical as vanishingly little is known about the molecular basis for septins as scaffolds. In theme 3, we will examine how the number of nuclei is kept in balance with the volume of cytoplasm in large multinucleate cells. This is important because pathologies are associated with aberrant ratios and how all cells sense their size remains a challenging cell cycle puzzle. Finally, in theme 4, to better understand the functions that emerge from syncytial cell organization, we will assess to what extent nuclei share or subdivide tasks within the communal cytosol. The flexibility in where and when genes are expressed, combined with the ability of nuclei to move between different parts of a cell, may be in part the basis for the wide-spread existence of syncytial cells in the biosphere. In this work, we will enrich our understanding on form and function of syncytia and illuminate cell organization mechanisms relevant to all cells.
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