Archive by category | Biological_approaches

[Research highlight] Transcription in action

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

[Research highlight] Laws of microbial growth

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

[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

[Research highlight] Mycoplasma rebooted

Upshot of a series of four papers published over the last years (Gibson et al, 2010, Lartigue et al, 2009, Gibson et al, 2008, Lartigue et al, 2007), J. Craig Venter’s team now reports the successful transplantation of a chemically synthesized genome into a host bacterial cell (Gibson et al, 2010). As proof of principle, a slightly altered Mycoplasma mycoides genome (JCVI-syn1.0) was synthesized, assembled and transplanted into M. capricolum recipient cells.  Read more

Keystone Symposium – Omics Meets Cell Biology (II)

Keystone Symposium – Omics Meets Cell Biology (II)

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

Keystone Symposium – Omics Meets Cell Biology (I)

Keystone Symposium – Omics Meets Cell Biology (I)

At the Keystone Symposium ‘OMICS Meets Cell Biology’, held this week in Breckenridge, Colorado, attendees had initially to face two major challenges: the first was to survive the cocktail mixing jet lag and altitude sickness and the second one—oh, it hurts!— was to resist the temptation to just forget all about science and focus exclusively on the concepts revolving around snow, slopes and fun sports…  … Read more

The role of neutral mutations in the evolution of phenotypes

The role of neutral mutations in the evolution of phenotypes

In a recent opinion piece, Andreas Wagner tries to reconcile the tension between proponents of neutral evolution and selectionism (Wagner 2008). He argues that “neutral mutations prepare the ground for later evolutionary innovation”. Wagner illustrates this point using a network model of genotype-phenotype relationships (Wagner 2005). In a so-called ‘neutral network’, nodes correspond to distinct genotypes associated with the same phenotype and are connected by an edge if the respective genotypes differ only by a single mutation event (eg point mutation). Examples of neutral networks include different genotypes coding for RNA or protein structures. In this representation, highly connected networks correspond to robust phenotypes that are not very sensitive to changes in genotype. Wagner notes the zinc finger fold as an impressive example of a highly connected neutral network as its structure remains essentially the same even after mutating all but seven of its 26 residues to alanine.  Read more