Archive by category | Research Highlights

[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] modENCODE releases extensive functional investigation of fly and worm genomes

Recently, a series of publications by members of the modENCODE consortium were released online at Science, Nature, and Genome Research. These works collectively describe a massive effort to functionally characterize and annotate the Drosophila melanogaster and Caenorhabditis elegans genomes, including in-depth analyses of genes and transcripts, epigenetic marks, transcription factor binding, and replication timing, across a range of developmental and tissue sources.  Read more

[Research highlight] Multicellular computers

Elaborate computation tasks can be performed by distributing the work across interconnected elementary information processing units. This principle underlies not only the operation of integrated electronic circuits, but also of many biological processes including development and, of course, the activity of the brain.  Read more

The role of neutral mutations in the evolution of phenotypes

The role of neutral mutations in the evolution of phenotypes

Research highlight by Pedro Beltrao, University of California, San Francisco 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  … Read more

Rewiring E. coli transcriptional network

Rewiring E. coli transcriptional network

Research highlight by Kazuharu Arakawa and Masaru Tomita, Institute for Advanced Biosciences, Keio University, Japan Gene duplications and mutations are central driving forces in the evolution of genomes. Genomes must be robust to such changes in order to be evolvable, and many studies have probed genome robustness using systematic gene knockouts or overexpression experiments. In a recent paper, Isalan et al. (2008) took a new approach to test the robustness of Escherichia coli gene circuitry by reconstructing gene duplication events by shuffling the promoter-ORF pairs for about 300 transcription factors and introducing 598 recombined pairs one-by-one into E. coli to  … Read more

A refreshing model: peppermint terpenoids

A refreshing model: peppermint terpenoids

Research highlight by Doron Lancet, Crown Human Genome Center, Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel 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  … Read more

EGFR and c-Met core signaling network

EGFR and c-Met core signaling network

Research highlight by Jeongah Yoon and Thomas S. Deisboeck, Massachusetts General Hospital, Charlestown, MA 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). The recent study by Guo et al (2008) aims to shed more light on the causes for such selective drug sensitivity by investigating the  … Read more

Transcription paused and poised for regulation

Transcription paused and poised for regulation

Research highlight by Frank C.P. Holstege, Department of Physiological Chemistry, University Medical Center Utrecht, the Netherlands. For eukaryotes, it is widely thought that transcription is primarily regulated through recruitment of the essential machinery to transcription start-sites. Previous hints challenging this paradigm have been confirmed by recent analyses showing that transcription regulation of a large number of genes actually occurs after recruitment. Mechanistically, such studies have gone furthest in Drosophila melanogaster (Muse et al, 2007; Zeitlinger et al, 2007). Here, conservative estimates indicate that more than 10% of genes are regulated through promoter-proximal pausing. On such genes, RNA polymerase II is  … Read more