Archive by category | Quantitative

[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

Fascinating correlations or elegant theories?

Chris Anderson, Editor-in-Chief of Wired , wrote a few weeks ago a provocative piece “”http://www.wired.com/science/discoveries/magazine/16-07/pb_theory”>The End of Theory: The Data Deluge Makes the Scientific Method Obsolete“, arguing that in our Google-driven data-rich era (”The Petabyte Age”) the good old “approach to science —hypothesize, model, test — is becoming obsolete”, leaving place to a purely correlative vision of the world. There is a good dose of provocation in the essay and it was quite successful in spurring a flurry of skeptical reactions in the blogosphere, FriendFeed-land and lately in Edge’s Reality Club.  Read more

A refreshing model: peppermint terpenoids

A refreshing model: peppermint terpenoids

Living cells are typically asymmetric, having tens of thousands different biopolymers (proteins and polynucleotides), but merely <1000 types of small molecules, such as amino acids and lipids. An exception is certain plant cells that harbor members of ~40,000 strong group of low molecular weight terpenoids, often displaying a complex compositional balance essential for plant growth and survival (Aharoni et al, 2005). Understanding the intricacies of biosynthesis and interconversion of such unusual cellular components appears to require the full power of Systems Biology. In a recent paper, Rios-Estepa et al (2008) harness a systems approach, including iterative cycles of mathematical modeling and experimental testing, to help elucidate the metabolic dynamics of the terpenoid universe.  Read more

EGFR and c-Met core signaling network

EGFR and c-Met core signaling network

Targeting receptor tyrosine kinases (RTKs) is currently thought to be a promising anti-cancer strategy (Baselga, 2006). However, clinical trials with RTK inhibitors demonstrated that some solid tumors are sensitive to these drugs while others are not. For instance, only a subset of non small cell lung cancer (NSCLC) tumors with EGFR-activating mutations seems to respond to EGFR inhibitors (Lynch et al, 2004).  Read more

Morphogen Paradoxes

Morphogen Paradoxes

A controversy seems to be brewing over some recent theories and quantitative analyses addressing the fundamental question of how the Bicoid morphogen gradient is established and decoded in early Drosophila embryos. The transcription factor Bicoid controls the anterior-posterior patterning of the developing embryo. It is translated from maternal mRNA localized at the anterior pole of the egg and its graded distribution activates, in a concentration-dependent manner, the expression of gap genes, thus determining their spatial domain of expression. Synthesis from a localized source combined with diffusion and uniform degradation of the Bicoid morphogen provides one of the simplest models to explain the approximately exponential shape of its gradient.  Read more

New feedback loop in Arabidopsis circadian clock

New feedback loop in Arabidopsis circadian clock

A new Science paper from the lab of Alex Webb (Dodd et al, Science, 2007) represents an important step forward in plant circadian research (read also commentary by Imaizumi et al, Science, 2007). The circadian (24 h) clock controls processes throughout the day and night in most organisms, and in plants is involved in multiple pathways including photosynthesis, leaf movement and floral opening. The circadian clock has evolved to consist of multiple interlocking transcriptional feedback loops (at least in eukaryotes), which generate the 24 h rhythm even under constant environmental conditions.  Read more

Glia-neuron interactions

Glia-neuron interactions

Nature Neuroscience has a nice special focus on glia and disease. The featured reviews and perspective articles discuss multiple aspects of neuron-glia interactions and their role in disease. The reason why I am highlighting this collection here is that I have the feeling that this field could potentially be a nice playground for systems biology.  Read more