Investigation of chromatin dynamics and their functional role in cell fate establishment

• Applicant: Dr. Jeffrey H. Stear
• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2008 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 106741258

The transcriptional and replicative activity of genomic DNA is directly related to the characteristics of the surrounding nucleoplasm. Recent work has suggested that global alterations in nuclear structure and dynamics play an important role in mediating large-scale transitions in nuclear activity. In particular, significant changes in nuclear plasticity and organization have been observed during development, as stem-cells transition into a more differentiated state. These results have led to the hypothesis that the nuclei of undifferentiated cells require increased structural flexibility in order to maintain their pluripotent nature. I will investigate this question by establishing a system to visualize the dynamic behavior of chromatin loci and nucleoproteins within the nuclei of developing C. elegans embryos. I will generate quantitative measurements of their motility by combining time-lapse microscopy with automated motion-tracking analysis. This data will be used to compare chromatin dynamics between the cells of different lineages and at successive developmental landmarks, which will allow me to directly test the hypothesis that nuclear plasticity fluctuates during the establishment of cell identity. Finally, I will investigate whether modulating chromatin dynamics plays a functional role in development by disrupting either nuclear organization or normal developmental progression, and characterizing the resulting effects.

• DFG Programme: Research Grants