Yaojun Zhang (PCTS Fellow, Wingreen lab)
“Genomic interactions in complex cellular environment”
Many processes in biology, from antibody production to tissue differentiation, require physical contact between distant genomic segments. Genomic interactions, especially long range genomic interactions, are complicated by the multi-level chromatin packing, the macromolecular crowding and active processes in the nucleus. How do DNA segments move and interact within such a complex nuclear environment? To address this question, we analyzed 3D trajectories from novel multi-color imaging measurements in live pro-B cells. We found that the motion of DNA segments is strongly subdiffusive. We propose that the formation of chromosomal domains is accompanied by a transition from a liquid-like state to a gel-like state. The resulting stable yet dynamic chromatin network creates a viscoelastic environment, which leads to the observed strongly subdiffusive motion. We used molecular dynamics simulations to demonstrate that such a mechanism can explain our experimental observations. Finally, we show that chromatin gelation dictates the encounter times of genomic interactions.
Sophia Li (Gitai lab)
“E. coli translation strategies differ across nutrient conditions”
For cells to grow faster they must increase their protein production rate. Microorganisms have traditionally been thought to accomplish this increase by producing more ribosomes to enhance protein synthesis capacity, leading to the linear relationship between ribosome level and growth rate observed under most growth conditions previously examined. Past studies have suggested that this linear relationship represents an optimal resource allocation strategy for each growth rate, independent of any specific nutrient state. Here we investigate protein production strategies in continuous cultures limited for carbon, nitrogen, and phosphate, which differentially impact substrate supply for protein versus nucleic acid metabolism. Unexpectedly, we find that at slow growth rates, E. coli achieves the same protein production rate using three different strategies under the three different nutrient limitations. Upon phosphate (P) limitation, translation is slow due to a particularly low abundance of ribosomes, which are RNA-rich and thus particularly costly for phosphorous-limited cells. In nitrogen (N) limitation, translation is slowed by limited glutamine and stalling at glutamine codons, resulting is slow elongation. In carbon (C) limitation, translation is slowed by accumulation of inactive ribosomes not bound to mRNA. These extra ribosomes enable rapid growth acceleration upon nutrient upshift. Thus, bacteria tune ribosome usage across different limiting nutrients to enable balanced nutrient-limited growth while also preparing for future nutrient upshifts