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1. Nuclear anarchy: timing variability in the cell division cycle

Genetically identical cells in the absence of any perturbations or stress will take different amounts of time to go through one round of division. We study the molecular roots of this timing variation, a fundamental but not well understood feature of the cell division cycle. We combine genetics, microscopy and computational approaches in several model systems including the filamentous fungus Ashbya and the budding yeast, S. cerevisiae. In the movie below, you can see the multinucleate, filamentous fungus Ashbya gossypii growing under the microscope.  Nuclei are green but have been false colored blue when they divide. Nuclei divide with different timing and independently of their neighbors.  In Ashbya, timing variability in the division cycle exists even in a common cytoplasm. 

Our work on this problem focuses on finding the sources of timing variation and understanding how nuclei can act autonomously in one cytoplasm.  We are developing MATLAB-based tracking methods and spatial statistical approaches to analyze nuclear pedigrees from within timelapse image data.  With these approaches, we are addressing if the sources of timing variation are stochastic or programmed into the cell division cycle.  Quantitative analysis of the position of cell cycle transcripts and diffusion of proteins between nuclei is enabling us to address if nuclei are competing for a common pool of resources or are functionally insulated from one another. 



2. Septin assembly and organization from yeast to mammals

Cytoskeletal polymer systems assemble into diverse and dynamic arrays for proper cell structure and function. The septins are a highly conserved component of the cytoskeleton that are important for processes such as cytokinesis, membrane compartmentalization, and exocytosis. These filament-forming, GTP-binding proteins are widely expressed from fungi to mammals, where they are especially enriched in the mammalian brain. Septins come together in cells to build higher-order structures such as rings, bars, and fibers. Despite the ubiquity and central role of septins in fundamental cell processes and disease, there are substantial gaps in our understanding of the mechanisms driving septin polymer assembly, dynamics and function in vivo. We have applied and developed novel imaging approaches to analyze septin organization in cells with diverse septin assemblies, functions and shapes. 

Our work on this problem has led to the development of new polarized fluorescence microscopy approaches with collaborator Rudolf Oldenbourg at the Marine Biological Laboratory in Woods Hole, MA.  In the movie below you can see septins at the budding yeast neck going through a splitting transition for cytokinesis.  The lines on the left of the image and the colors on the right represent the orientation of the dipole moments of the population of GFPs.  We analyzed the orientation of the GFP fused to septins through this transition and found septins dramatically change organization in this transition in a matter of minutes.  We are now looking at individual septin molecules during this transition to understand the basis of this swift reorientation.





Last Updated: 12/21/11