In an article recently published in Science, Isaacs et al describe the replacement of all 314 TAG stop codons in the Escherichia coli genome with synonymous TAA codons, representing an unprecedented effort in large-scale genome editing. Read more
In a work just published at Nature, Churchman and Weissman (2011) describe a new method for directly capturing and sequencing elongating, or nascent, RNA transcripts. The authors then use this method to provide a detailed look at the transcriptional process in action, revealing a histone modification-dependent mechanism that constrains genome-wide antisense transcription, and pervasive transcriptional pausing and backtracking throughout genes. Read more
In a work recently published in Science, Scott et al reveal a series of microbial “growth laws” that describe simple relationships between translation, nutrition, and cellular growth. They show that these laws hold across different experimental perturbations and E. coli strains, and, ultimately, provide a phenomenological model describing the delicate balancing act cells maintain when deciding how much of their proteome to allocate to ribosome-related processes. Read more
This last August 11-14, systems biologists convened in beautiful Santa … Read more
In a report published this week at Nature, Tay et al. reveal that populations of mouse 3T3 cells exposed to TNF-α show a digital NF-κB response, where increasing TNF-α concentrations lead to a higher proportion of cells with nuclear localized NF-κB — an effect that depends, in part, on pre-existing heterogeneity within the cell population. These results provide another compelling example of the way that studies using single cell measurements are transforming our understanding of cellular signaling mechanisms. Interestingly, these results seem to contrast with another recent single-cell-based study of NF-κB dynamics (Giorgetti et al. 2010), which observed a relatively uniform population-level NF-κB response to TNF-α in human HCT116 cells, indicating that there is still much to learn about the dynamics of NF-κB signaling. Read more
Animal genomes are littered with conserved non-coding elements (CNEs)—most of which represent evolutionarily constrained cis-regulatory sequences—however, it is often not clear why these sequences are so exceptionally conserved, since anecdotal examples have shown that orthologous CNEs can have divergent functions in vivo (Strähle and Rastegar 2008; Elgar and Vavouri 2008). In an article recently published in Molecular Biology & Evolution, Ritter et al. compare the functional activities of 41 pairs of orthologous conserved non-coding elements (CNEs) from humans and zebrafish (2010). Interestingly, sequence similarity was found to be a poor predictor of which CNEs had conserved function. In contrast, the authors found that measuring transcription factor binding site change, instead of simple sequence divergence, improves their ability to predict functional conservation. Read more
Before I carry on with a summary of the second part of the Keystone Symposium ‘Omics Meets Cell Biology’, I should clarify that this post and the previous one dedicated to this conference are not intended to provide an comprehensive account of all the talks but rather to communicate some general (and subjective) impressions of the meeting. To keep these posts reasonably short (and sometimes due to a lack of memory…), I had to omit several of the excellent presentations given at this meeting. The full program and complete list of speakers is available at the Keystone Symposium website. Read more