[Research highlight] NF-kappaB signaling goes digital

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

[Research highlight] Cis-regulatory evolution, not so mysterious after all?

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

Editors’ conference agenda

I spent May 14-15th at the Symposium on Integrative Network Biology and Cancer, hosted by the Institute of Cancer Research in London. The organizers, Chris Bakal and Rune Linding, managed to attract a stellar speakers list, and I had great discussions with many of the attendees. Inspired by this, I thought it could be useful to share a tentative list of conferences in 2010 that will be attended by the Molecular Systems Biology editors. If you happen to be at one these conferences, we would be delighted to meet you in person and hear about your research.  Read more