Tara Oceans back home

Tara sailed more than 60,000 miles.

The Tara Oceans expedition (oceans.taraexpeditions.org) just arrived last Saturday in Lorient, France, after sailing across the seas of the planet for more than 2 years, collecting samples of planktonic life and recording physical, geographical and climatic parameters in a systematical manner over a total of 153 stations.

A couple of weeks ago, on March 13, we were fortunate to be able to join Eric Karsenti who had just boarded Tara in the Azores. In this interview (listen) and an accompanying invited Editorial “Towards an Oceans Systems Biology” (Karsenti, 2012), Eric explains how the data collected by the expedition will help “understanding how populations of organisms are structured by their interaction with the environment and how such complex systems have evolved” in the marine ecosystem.

The integration of the collected biological and geochemical data into predictive models will represent a formidable challenge and will necessitate the development of appropriate analyses methods (Raes et al, 2011). But preliminary results already indicate that the data will provide exciting insights into the biodiversity of the marine environment: “it looks like there are many more eukaryotic species than bacteria and 90% of these species are unknown”.

Beyond its scientific outcome, the philosophy of the expedition was also to “promote broader thinking” by revealing the interdependence between marine life and environment and thus reminding us “we all depend on each other on this planet”.

A nice lesson in systems biology!

Karsenti E (2012) Towards an ‘Oceans Systems Biology’. Mol Syst Biol 8:575

Raes J, Letunic I, Yamada T, Jensen LJ & Bork P (2011) Toward molecular trait-based ecology through integration of biogeochemical, geographical and metagenomic data. Mol Syst Biol 7:473

New Synopsis with ‘Visual Titles’

Proteomic and protein interaction network analysis of human T lymphocytes during cell-cycle entryThe clock gene circuit in Arabidopsis includes a repressilator with additional feedback loopsCompeting pathways control host resistance to virus via tRNA modification and programmed ribosomal frameshifting

Molecular Systems Biology has recently updated and streamlined its article Synopsis format (see example in Orr et al, 2012).

Each research article is now accompanied by a Synopsis box that includes an illustrative graphic, which we call a “Visual Title,” along with a short description of the main findings of the work. The Visual Titles are designed to provide, at a glance, an intuitive illustration of the general topic of the work. Featured articles on our main homepage have always been highlighted with graphics of this nature, but now every article will be permanently accompanied by a Visual Title.

The Synopsis format has also been substantially streamlined—we have eliminated the longer “Extended Synopsis” text summaries, and have moved the Synopsis to the beginning of the full text article page, rather than on a separate page.

Synopses will thus provide a concise and attractive overview of the key points made in a paper. We hope you will enjoy this new feature.

Editors’ Conference Calendar 2012

Below is a list of the conferences the Molecular Systems Biology editors will be attending in 2012.

Conference Place Date Editor
EMBL: Omics and Personalised Health Heidelberg Feb. 16-18 TL & ALH
Keystone: Complex Traits, Genomics and Computational Approaches Breckenridge Feb. 20-25 ALH
International Conference on the Systems Biology of Human Disease Heidelberg May 2-4 TL
CSHL: Systems Biology, Global Regulation of Gene Expression Cold Springs Harbor Mar. 20-24 TL
Keystone: Proteomics, Interactomes Stockholm May 7-12 ALH
The Sixth q-bio Conference Santa Fe Aug. 8-12 ALH
The 13th International Conference on Systems Biology Toronto Aug. 19-23 TL
HUPO 2012 Boston Sep. 9-13 ALH
EMBO: From Functional Genomics to Systems Biology Heidelberg Nov. 17-20 TBA

TL: Thomas Lemberger, ALH: Andrew L Hufton, TBA: to be announced

As usual, this schedule is subject to change, and we recognize that there are many excellent conferences that we will not be able to attend this year due to scheduling limitations.

What is your top 2011 MSB paper?

Below is a list of the top 10 most read research articles published in Molecular Systems Biology in 2011, based on combined HTML and PDF access.  The work by Saeidi et al, in particular, received widespread media coverage for making a practical first-step toward fighting infections with engineered microbes (e.g. at Science NOW, Ed Yong’s blog at Discover Magazine, Nature, and TheScientist).

What is your personal top article of 2011?  Please post your comments below.



Engineering microbes to sense and eradicate Pseudomonas aeruginosa, a human pathogen
Nazanin Saeidi, Choon Kit Wong, Tat-Ming Lo, Hung Xuan Nguyen, Hua Ling, Susanna Su Jan Leong, Chueh Loo Poh & Matthew Wook Chang



Predicting selective drug targets in cancer through metabolic networks
Ori Folger, Livnat Jerby, Christian Frezza, Eyal Gottlieb, Eytan Ruppin & Tomer Shlomi



Characterizing the role of miRNAs within gene regulatory networks using integrative genomics techniques
Wan-Lin Su, Robert R Kleinhanz & Eric E Schadt



RNA sequencing reveals two major classes of gene expression levels in metazoan cells
Daniel Hebenstreit, Miaoqing Fang, Muxin Gu, Varodom Charoensawan, Alexander van Oudenaarden & Sarah A Teichmann



The essential genome of a bacterium
Beat Christen, Eduardo Abeliuk, John M Collier, Virginia S Kalogeraki, Ben Passarelli, John A Coller, Michael J Fero, Harley H McAdams & Lucy Shapiro



Dynamic transcriptome analysis measures rates of mRNA synthesis and decay in yeast
Christian Miller, Björn Schwalb, Kerstin Maier, Daniel Schulz, Sebastian Dümcke, Benedikt Zacher, Andreas Mayer, Jasmin Sydow, Lisa Marcinowski, Lars Dölken, Dietmar E Martin, Achim Tresch, Patrick Cramer



The quantitative proteome of a human cell line
Martin Beck, Alexander Schmidt, Johan Malmstroem, Manfred Claassen, Alessandro Ori, Anna Szymborska, Franz Herzog, Oliver Rinner, Jan Ellenberg & Ruedi Aebersold
(see also Nagaraj et al)



Network modeling of the transcriptional effects of copy number aberrations in glioblastoma
Rebecka Jörnsten, Tobias Abenius, Teresia Kling, Linnéa Schmidt, Erik Johansson, Torbjörn E M Nordling, Bodil Nordlander, Chris Sander, Peter Gennemark, Keiko Funa, Björn Nilsson, Linda Lindahl & Sven Nelander



Proteomic snapshot of the EGF-induced ubiquitin network
Elisabetta Argenzio, Tanja Bange, Barbara Oldrini, Fabrizio Bianchi, Raghunath Peesari, Sara Mari, Pier Paolo Di Fiore, Matthias Mann & Simona Polo



Proteome-wide systems analysis of a cellulosic biofuel-producing microbe.
Andrew C Tolonen, Wilhelm Haas, Amanda C Chilaka, John Aach, Steven P Gygi & George M Church

Matthias Mann awarded Louis-Jeantet Prize for medicine

The Louis-Jeantet Foundation awarded its prestigious 2012 Louis-Jeantet Prize for medicine to Matthias Mann last Tuesday, Jan 24th, for his contributions to mass spectrometry and the field of proteomics.  Matthias Mann, Director of the Department of Proteomics and Signal Transduction at the Max-Planck Institute of Biochemistry in Martinsried, and his co-workers have developed several of the key technologies that have made modern proteomics possible, including mass spectrometry-based identification of proteins from electrophoretic gels and the SILAC method that underlies many recent quantitative proteomics studies. The foundation highlighted, in particular, his quantitative analyses of cancer cell proteomes, and the promise this work may hold for the future diagnosis and treatment of cancer (e.g. Geiger et al, 2010; Lundberg et al, 2010; Nagaraj et al,  2011).

The 2012 Louis-Jeantet Prize for medicine was also awarded to Fiona Powrie for her work on immunity and host-pathogen interactions within the mammalian gut.  Mann and Powrie will each be awarded CHF 700,000, with the majority of these funds going to help continue these scientists’ research programs.

EMBO Molecular Medicine recently published a related editorial, and contributions from both Mann and Powrie that provide some personal insight into the research paths that led to these important discoveries.

Geiger T, Cox J, Mann M (2010) Proteomic changes resulting from gene copy number variations in cancer cells. PLoS Genet 6: e1001090

Lundberg E, Fagerberg L, Klevebring D, Matic I, Geiger T, Cox J, Algenäs C, Lundeberg J, Mann M, Uhlen M (2010) Defining the transcriptome and proteome in three functionally different human cell lines. Mol Syst Biol 6: 450

Nagaraj N, Wisniewski JR, Geiger T, Cox J, Kircher M, Kelso J, Pääbo S, Mann M (2011) Deep proteome and transcriptome mapping of a human cancer cell line. Mol Syst Biol 7: 548

[Research highlight] Life re-coded

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.

The scientists first replaced all TAG codons in batches of ten codons across 32 separate strains using their previously-published MAGE method (Wang et al, 2009). These edited genome segments were then progressively combined using a new conjugation-based genome assembly method (CAGE). They have currently produced four strains that each have a quarter of their TAG stop codons replaced, and they hope to produce the complete TAG replacement strain in the near future. Somewhat surprisingly, no severe phenotypic consequences were observed in these replacement strains, indicating that the TAG codon is not essential, despite its near-universal presence in the genetic code of all organisms.

Indeed, the only exception to the universality of the TAG stop codon is a small selection of methanogenic archaea, and one bacterium, in which TAG encodes for the non-canonical amino acid, pyrrolysine (reviewed in Krzykci et al, 2005). Following nature’s lead, the authors hope that once they have produced the complete TAG replacement strains, they will then be able to use this free codon as a “plug-and-play” system for incorporating unnatural amino acids into proteins.

More broadly, this technology will provide an attractive alternative to wholesale chemical genome synthesis when researchers need to systematically introduce multiple genetic alterations into a genome, especially since current synthetic organism designs hew closely to natural organisms. This work may also be a first step towards creating organisms with completely rewritten genetic codes. Such fully “re-coded” organisms would have an inherent genetic “fire-wall” since they would not be able to share their genetic material via horizontal transfer or be infected by naturally occurring viruses.

Isaacs FJ, Carr PA, Wang HH, Lajoie MJ, Sterling B, Kraal L, Tolonen AC, Gianoulis TA, Goodman DB, Reppas NB, Emig CJ, Bang D, Hwang SJ, Jewett MC, Jacobson JM, Church GM (2011) Precise manipulation of chromosomes in vivo enables genome-wide codon replacement. Science 333: 348-53

Krzycki JA (2005) The direct genetic encoding of pyrrolysine. Curr Opin Microbiol 8: 706-12

Wang HH, Isaacs FJ, Carr PA, Sun ZZ, Xu G, Forest CR, Church GM (2009) Programming cells by multiplex genome engineering and accelerated evolution. Nature 460: 894-8

Updated Instructions for Authors

Molecular Systems Biology has recently completed a major update of its Instructions for Authors. Of particular importance, this new document now fully incorporates information about our policies regarding transparency in scientific publishing. Molecular Systems Biology, along with the other EMBO Publications journals, has made a strong commitment to promoting transparency in the editorial process, and recently began publishing a Review Process File, containing anonymous reviewers’ reports, authors’ rebuttal letters, and the editor’s decisions, with accepted manuscripts. In addition, we have been working to promote greater availability, transparency, and re-usability for scientific data associated with published works. For more details on these efforts please see our editorial, “From bench to website.”

Data transparency

For some time now, Molecular Systems Biology has allowed authors to submit source data that directly supports a particular figure panel. Links to these data are then included in the html manuscript version, directly below the associated figures, so that readers can easily discover and reuse data that is of interest to them. This feature can be used both for numeric results (e.g. supporting a graph), or for more structured data types (e.g. SBML model files). Information regarding how source data for figures should be prepared, what types of data can be accommodated, and how to submit these files in our manuscript submission system, is now included in the Instructions for Authors.

Data deposition

Molecular Systems Biology, requires that authors submit data to public repositories according to community standards, and strongly encourages them to do so before manuscript submission. Our Instructions for Authors now provides information regarding our standards for a variety of data types, including functional genomics, proteomics, molecular interactions, and computational models.

Other improvements

These publishing policies and standards have grown out of extensive discussion with members of the scientific community, and we are eager to receive any comments or feedback you may have.

Editors’ Conference Agenda – 2011

Here is a preliminary list of conferences that the Molecular Systems Biology editors will be attending in 2011. We are looking forward seeing a lot of the Alps this year, with meetings in Innsbruck, Geneva, and Vienna. And, of course, we also looking forward to meeting Molecular Systems Biology’s readers and authors; if you are attending one of these conferences or workshops, we would be quite happy to chat with you and learn about your research.

Naturally, this schedule is subject to change, and we recognize that there are many excellent conferences that we will not be able to attend this year due to scheduling limitations.

Conference Place Date Who
FEBSX-SysBio2011 Innsbruck Feb. 26-Mar. 3 ALH
CSHL Systems Biology: Networks Cold Spring Harbor Mar. 22-26 TL
International Conference on Systems Biology of Human Disease Boston June 22-24 TL
ISMB/ECCB Vienna July 17-19 ALH
Gordon Conference – Cellular Systems Biology Davidson July 24-29 TL
The Fifth q-bio Conference on Cellular Information Processing Santa Fe Aug. 10-13 ALH
12th International Conference on Systems Biology Heidelberg/Mannheim Aug. 28-Sept. 1 TL
HUPO 2011 Geneva Sept. 4-7 ALH
The EMBO Meeting Vienna Sept. 10-13 TL
EMBO | EMBL Symposium: Structure and Dynamics of Protein Networks Heidelberg Oct. 13-16 TL & ALH

TL: Thomas Lemberger, ALH: Andrew L. Hufton

[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.

The work adds to a rapidly expanding functional genomics toolkit that allows researchers to dissect evermore precise steps in the Central Dogma — the DNA to RNA to protein cascade that transforms genomic information into cellular function. See also the recent work by Cramer and colleagues that describes a method for quantifying genome-wide mRNA synthesis and decay rates (Miller et al, 2011), and the ribosome profiling technique, also developed in the Weissman lab, which can provide genome-wide views of protein translation (Ingolia et al, 2009).

Churchman LS & Weissman JS (2011) Nascent transcript sequencing visualizes transcription at nucleotide resolution. Nature 469: 368–373

Ingolia NT, Ghaemmaghami S, Newman JR, Weissman JS (2009) Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 324:218-23

Miller C, Schwalb B, Maier K, Schulz D, Dümcke S, Zacher B, Mayer A, Sydow J, Marcinowski L, Dölken L, Martin DE, Tresch A, Cramer P (2011) Dynamic transcriptome analysis measures rates of mRNA synthesis and decay in yeast. Mol Syst Biol 7:458

[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.

Integrated analyses of these data are described in two articles released at Science (Gerstein et al, 2010; modENCODE Consortium et al, 2010). These works provide compelling support for the existence of highly occupied target regions (HOT) regions — regions of the genomes that bind a complex mix of many transcription factors, but whose connection with gene regulation is still largely unclear — and, show that the dense epigenetic datasets can be used to segment the genomes into “chromatin states” that have distinct functional properties (see also the recent work by Filion et al, 2010)

In a related Perspective, Mark Blaxter, declares that these works have provide an important step toward the ability “to compute an organism from its genome” (Blaxter 2010). A prime example of progress toward this goal is provided by the particularly comprehensive genomic regulatory network built by the Drosophila modENCODE team, which is inferred from a combination of ChIP-based transcription factor binding, sequence motifs, epigenetic marks, and coexpression (modENCODE Consortium et al, 2010). A relatively simple linear combination of predicted regulatory inputs can predict the expression of about one quarter of the transcriptome with some accuracy. In addition, the authors find that the remaining unpredictable genes tend to have noisier expression levels, suggesting that they may be intrinsically more weakly regulated.


Blaxter M (2010) Genetics. Revealing the dark matter of the genome. Science 330:1758-9

Filion GJ, van Bemmel JG, Braunschweig U, Talhout W, Kind J, Ward LD, Brugman W, de Castro IJ, Kerkhoven RM, Bussemaker HJ, van Steensel B (2010) Systematic protein location mapping reveals five principal chromatin types in Drosophila cells. Cell 143:212-24

Gerstein MB, Lu ZJ, Van Nostrand EL, Cheng C, Arshinoff BI, Liu T, Yip KY, Robilotto R, Rechtsteiner A, Ikegami K, Alves P, Chateigner A, Perry M, Morris M, Auerbach RK, Feng X, Leng J, Vielle A, Niu W, Rhrissorrakrai K et al (2010) Integrative Analysis of the Caenorhabditis elegans Genome by the modENCODE Project. Science 330:1775-1787

modENCODE Consortium, Roy S, Ernst J, Kharchenko PV, Kheradpour P, Negre N, Eaton ML, Landolin JM, Bristow CA, Ma L, Lin MF, Washietl S, Arshinoff BI, Ay F, Meyer PE, Robine N, Washington NL, Di Stefano L, Berezikov E, Brown CD et al (2010) Identification of Functional Elements and Regulatory Circuits by Drosophila modENCODE. Science 330:1787-1797