The MolBio Carnival: the first edition

I’m pleased to host the very first edition of the MolBio Carnival, your monthly roundup of interesting posts in molecular biology from the science blogosphere. There has been a great response to this initiative and I had a great time reviewing submissions and writing this post.

You can read all about this Carnival here (submission guidelines, scope, etc), but right now, let’s get down to business, as we have a very exciting first edition:

1) Leucocite recruitment to injured tissue is an important feature of the inflammatory response. The mechanism mediating this recruitment, however, is largely unknown. Becky Ward at It Takes 30, highlights an interesting Science paper describing that in zebrafish, a hydrogen peroxide (H2O2) concentration gradient is produced at the wound margin and it appears to act as a signal for rapid leukocyte recruitment.

2) On a second submission, Becky discusses a provocative article addressing the molecular basis of the association of a particular HLA allele, HLA-B57, with HIV “elite controllers” (HIV-infected individuals that maintain very low levels of HIV RNA without therapy and that generally do not progress to AIDS). Briefly, the peptide-binding characteristics of HLA-B57 molecules appears to affect thymic development in a way that it leads to a more cross reactive B57-restricted T cell repertoire.

"The bottom line is that any HIV peptide that binds to HLA-B57 (…) is going to have a much harder time finding a mutation that will evade the immune response. And this would explain why people who are lucky enough to have HLA-B57 among their class I MHC molecules would be better at controlling HIV infection"

3) Stem cells divide asymmetrically which allows preserving stem cell number while generating differentiated cells. Kat at Science Update blog, from Cancer Research UK, discusses a fascinating article in which the authors show that mouse intestinal stem cells appear to have a characteristic mitotic spindle orientation. Notably, this orientation appears to correlate with the asymmetric distribution of labeled DNA, supporting the idea that Cairns’ “immortal strand” hypothesis could be applied to stem cells of the gut epithelium. Further, the authors provide evidence for an important role of adenomatous polyposis coli tumor suppressor (Apc) in this process.

Figure from Kat's post highlighting the importance of APC in the asymmetric division of stem cells

4) Methods that allow us to calculate the affinity of a small molecule with a protein can be of great importance to the discovery of new drugs and biological probes, and for chemical genomics. Nir London at the Macromolecular Modeling Blog, reviews in an expert-level fashion, a number of different methods to answer the following question: Can we predict small-molecules binding affinities?

5) Circadian clocks control a large number of daily processes in most organisms. These endogenous cellular timekeepers regulate rhythms in gene expression, physiology and behaviour and enable organisms to anticipate predictable environmental variations. Despite the wealth of knowledge concerning the functioning of central oscillators, little is known about the mechanisms that allow them to temporally control gene expression and the activity of different clock targets. Here at MolBio Research Highlights, I discuss an article in which the authors use a clever genetic strategy to characterize circadian output pathways using the model organism Neurospora crassa.

6) Caloric restriction has been shown to increase lifespan and protect against metabolic disease. Michelle over at C6H12O6 comments on an interesting paper in which the authors develop a mouse model of glioblastoma multiforme, one of the “most aggressive and invasive forms of primary human brain cancer”, and tested the efficacy of caloric restriction for its ability to reduce tumour size and invasion.

From her post:

“As it seems, caloric restriction decreases tumor spread and angiogenesis in a malignant brain cancer mouse model. This is strong evidence that cancer cells have difficulty proliferating under metabolic stress, even when healthy cells are functioning normally”

7) Igor Ulitsky, at You'd Prefer An Argonaute, discusses a nice recent article in PLoS Biology reporting that in contrast to what has been suggested by earlier studies, the proportion of 'dark matter' transcription in mammalian genomes appears to be much lower than previously thought. The authors conclude that tiling array approaches to surveying the transcriptome are prone to false positives, and by performing RNA-Seq, they show that many of the tags that fall outside the annotated regions of the genome appear to be somehow associated with known genes, or as Igor puts it:

“(..) about 80% of those reads fall within 10kb of known genes and are likely to represent either unannotated parts of those genes, or transcripts whose biogenesis function is related to the gene adjacent to them, as their expression is generally highly correlated with their neighbors"

8) Iddo Friedberg at Byte Size Biology discusses a Nature paper describing the fascinating functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene PTENP1, and the consequences of this interaction. Briefly, the 3’ UTR of PTEN and PTENP1 are very similar and have conserved seed sequences for interacting with several miRNAs. Notably, the authors show that PTENP1 3′ UTR can act as a decoy of PTEN-targeting miRNAs, thereby enhancing the levels of this tumour suppressor.

9) I have previously stated in my blog that the different steps in gene expression are stochastic biochemical events and that this randomness can lead to substantial cell-to-cell variability in RNA and protein levels that can have phenotypic consequences even within a clonal population of cells. On a fascinating and provocative post, Pablo Astudillo at Astu’s Science Blog, discusses biological heterogeneity, noise and buffering, in the context of developmental biology, reviewing several interesting articles.

Noise control in a theoretical embryo (From Pablo's post)

10) Bacteria in the phylum Planctomycetes have fascinating and unsual properties, including budding reproduction, sterol biosynthesis, absence of cell wall peptidoglycan, and notably, intracellular membrane-bounded compartments. It is also noteworthy that planctomycetes appear to have genes coding for proteins that are similar to “membrane coat proteins”, central players in the eukaryotic-specific process of endocytosis.

Lucas Brouwers at Thoughtomics (who will host the next edition of the MolBio Carnival), comments on a recent PNAS paper reporting the interesting discovery of an endocytic process in the planctomycete Gemmata obscuriglobus which appears to be similar to eukaryotic clathrin-mediated endocytosis. This may have important implications for our understanding of eukaryotic evolution.

“So where does that leave us? Endocytosis, comparmentalization and membrane sorting are no longer exclusive to eukaryotes.”

Gemmata obsuriglobus is capable of endocytosis!

11) From her new home at Field of Science, LabRat highlights a paper characterizing the mechanism herpes simplex virus uses to move around the cell in order to achieve efficient replication and pathogenesis. It appears that a number of viral proteins interact with cellular microtubule motors such as the inbound motor dynein and the outbound motor kinesin-1, which ultimately helps the virus get a free ride across the microtubule network.

“They found that several of the capsid proteins could bind to important transporter molecules, and furthermore that several different transporter molecules could sometimes bind to the same capsid protein”

12) To finish up the 1st issue of the MolBio Carnival, Bosco at Trapped in the U.S.A. tells us the story behind Amgen’s erythropoietin (EPO) patent, which includes corporate espionage and a Japanese scientist that must have gotten a pretty big check.

That's it for this month's edition of The MolBio Carnival. You can check future hosts and past editions at the Carnival’s index page. Be sure to subscribe to its RSS feed to receive notifications and summaries when new editions of the Carnival are posted.

Also, be sure to submit your best molbio blog articles,  using our carnival submission form, to the next edition of The Molbio Carnival, which will be hosted by Lucas Brouwers over at Thoughtomics. More info here.

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Here are some of the articles discussed in the posts featured in this edition of The MolBio Carnival:

Niethammer, P., Grabher, C., Look, A., & Mitchison, T. (2009). A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish Nature, 459 (7249), 996-999 DOI: 10.1038/nature08119

Quyn, A., Appleton, P., Carey, F., Steele, R., Barker, N., Clevers, H., Ridgway, R., Sansom, O., & Näthke, I. (2010). Spindle Orientation Bias in Gut Epithelial Stem Cell Compartments Is Lost in Precancerous Tissue Cell Stem Cell, 6 (2), 175-181 DOI: 10.1016/j.stem.2009.12.007

van Bakel H, Nislow C, Blencowe BJ, & Hughes TR (2010). Most "dark matter" transcripts are associated with known genes. PLoS biology, 8 (5) PMID: 20502517

Altschuler, S., & Wu, L. (2010). Cellular Heterogeneity: Do Differences Make a Difference? Cell, 141 (4), 559-563 DOI: 10.1016/j.cell.2010.04.033

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[Direct Connection] Sweet and Sour: Glucose-6-Phosphate, Anoxia, and Enzyme Regulation

The “Direct Connection” section of MolBio Research Highlights includes blog posts discussing primary research articles in the field, but the interesting thing about it is that these posts are written by the authors themselves. This allows them to discuss the background, results and implications of their work with a wider audience and in a more relaxed format. Further, as it provides a direct link between the authors and the scientific community (hence its name), it promotes discussion.

In today's "Direct Connection", Christopher Dieni, PhD, a postdoctoral scholar in the Department of Chemistry at Pennsylvania State University, discusses his recent publication entitled "Regulation of Glucose-6-Phosphate Dehydrogenase by Reversible Phosphorylation in Liver of a Freeze Tolerant Frog".

Sweet and Sour: Glucose-6-Phosphate, Anoxia, and Enzyme Regulation

A crazy model organism!

Grad school taught me a great many lessons, but I think many of them can be summarized in a brief and blunt statement: human beings aren’t that great!

Shocked?

Well, when you think about it, we’re not that cool of an organism at all. We’re extremely inefficient (biochemically speaking), and we’re really not that adaptable to… well… anything that perturbs our internal or external environment, however slight.

By stark contrast, my graduate lab, or more accurately the lab of Dr. Ken Storey at Carleton University in Ottawa, Ontario, Canada, studies a wide array of awesome animals -model organisms- that can withstand harsh environmental conditions. These include frogs and snails that survive the desert heat and dehydration, mammals that hibernate over the long winter, reptiles and amphibians that can get by for months on an oxygen-deprived environment and my personal favorite and the central model organism of my graduate work, the freeze-tolerant wood frog, Rana sylvatica, that can survive the freezing of ~70% of its extracellular and extra-organ water during the winter, and then thaw in the spring and continue about its normal life.

A notable thing about the wood frog’s survival mechanisms is that one molecule plays a key role in keeping the frog alive during its frozen, unfathomable state: glucose. Most people find it hard to believe that this simple and ubiquitous six-carbon sugar can have such a prominent role in this extraordinary organism and yet, evolutionarily speaking, it makes perfect sense. Take a molecule with such universality and harness it maximally, not only for its biochemical and metabolic properties, but for its physical properties as well. High intracellular glucose can act as a cryoprotectant, as it prevents both intracellular freezing and the loss of intracellular water to the extracellular environment caused by the osmotic imbalance of extracellular freezing.

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A clever genetic strategy for the study of circadian output pathways

Circadian clocks control a large number of daily processes in most organisms. These endogenous cellular timekeepers regulate rhythms in gene expression, physiology and behaviour and enable organisms to anticipate predictable environmental variations.

Circadian clocks are composed of a central oscillator and two signaling pathways: input pathways convey external signals to the oscillator, so that it can be synchronized with the environment and output pathways allow the oscillator to temporally regulate diverse cellular processes.

The ascomycete Neurospora crassa, instrumental to the history of molecular biology (See The Almighty Fungi: The Revolutionary Neurospora crassa), has one of the best-understood circadian systems, in which a molecular negative feedback loop involving FREQUENCY and the WHITE COLLAR (WCC) complex lies at its core. Briefly, the WCC directly activates transcription of frq, and levels of FRQ protein start then to build up. FRQ inhibits its own expression by modulating the activity of the WCC, which results in the daily oscillation of both the frq mRNA and protein levels, and ultimately, in the rhythmic expression of a variety of clock-controlled genes (ccgs).

Despite the extensive knowledge accumulated on the molecular basis of some eukaryotic oscillators, including Neurospora’s, and the identification of a number of ccgs, little is known about the mechanisms that allow central oscillators to temporally control gene expression and the activity of different clock targets.

In this post, I will discuss a fascinating article from the Bell-Pedersen lab aiming at characterizing circadian output pathways in Neurospora.

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Matryoshka dolls in biology, the connection between flowers, stem cells and fat and more, in my Picks of the Week from RB

Another week has gone by and some very interesting molbio blog posts have been aggregated to Researchblogging.org. Every week [see my opening post on the matter], I'll select some blog posts I consider particularly interesting in the field of molecular biology [see here to get a sense of the criteria that will be used], briefly describe them and list them here for you to check out.

Note that I'm only taking into consideration the molbio-related blog posts aggregated under "Biology". This issue includes articles from the last two weeks, as last week no Picks were posted.

Congratulations to everyone who got their post selected.

A recent paper from The Wellcome Trust Case Control Consortium, aiming to evaluate the role of copy number variants in genetic susceptibility to common diseases, concluded that common CNVs are “unlikely to contribute greatly to the genetic basis of common human diseases”.

Daniel MacArthur at Genetic Future finds this far from surprising and instead asks:

(…) why don't common CNVs play a major role in complex disease susceptibility?

Animals are generally home to a huge number of microorganisms and some of them establish beneficial symbiotic relationships with their hosts. Lucas Brouwers at Thoughtomics brings us a fascinating Matryoshka-like story of organisms and endosymbionts, discussing first a protist that inhabits the gut of some termites and later an endosymbiont called Blochmannia, which resides in the carpenter ant.

Organisms and their endosymbionts (Image credit)

All cells (including free-living organisms), can modulate their gene expression profiles in response to changes in their surroundings. In bacteria, extracellular signals are transduced into the cell predominantly by two-component systems, but “bacteria also contain multi-component systems, for both inter- and intra-cellular signaling” (See Bacterial signaling and studying diseases through exome sequencing, in my picks of the week from RB). Interestingly, “although Two-Component Systems (TCS) are found in all three superkingdoms of life (Archaea, Bacteria and Eukaryotes), they are suspiciously absent from the animal kingdom”.

LabRat tries to answer “why don't animals use TCSs?”


Ian York at Mystery Rays from Outer Space, comments on a recent paper reporting something that can easily be used in a House M.D. episode in the near future.

Mitochondria are derived from bacteria and “so might bear bacterial molecular motifs”. This Nature article shows, in Ian’s words, that “mitochondrial components, released from cells after damage, trigger innate immune responses through pathways that are more traditionally associated with pathogen-specific patterns” (my emphasis).
So, after cell disruption by trauma, these components can signal through innate immune pathways and create a sepsis-like state, but without infection!


“Flowers make fat and stars make bone”. This seemingly senseless phrase can be derived from a fascinating paper discussed by Rob Mitchum at Science Life, in which the authors set out to investigate if (and how) geometric shape cues can play a role in promoting the differentiation of mesenchymal stem cells to distinct lineages.

Geometric cues appear to have an important role in differentiation (Image credit)

Finally, in the last issue of Picks of the Week, I introduced a new category for my selections entitled “Honorable mention” (See "Dominant transposases, becoming famous for your lab mistakes and more, in my Picks of the Week from RB" for more details).

This week’s honorable mention goes to Merry Youle’s post on Small Things Considered, describing “holins”, small, phage-encoded integral membrane proteins that control the length of the infection cycle of some phages, by inducing the formation of holes in the bacterium's inner membrane after a determined period of time.

That's it for this week. Stay tuned for more MolBio Research Highlights!

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Some of the articles discussed in this week's selected posts:

Craddock, N., Hurles, M., Cardin, N., Pearson, R., Plagnol, V., Robson, S., Vukcevic, D., Barnes, C., Conrad, D., Giannoulatou, E., Holmes, C., Marchini, J., Stirrups, K., Tobin, M., Wain, L., Yau, C., Aerts, J., Ahmad, T., Daniel Andrews, T., Arbury, H., Attwood, A., Auton, A., Ball, S., Balmforth, A., Barrett, J., Barroso, I., Barton, A., Bennett, A., Bhaskar, S., Blaszczyk, K., Bowes, J., Brand, O., Braund, P., Bredin, F., Breen, G., Brown, M., Bruce, I., Bull, J., Burren, O., Burton, J., Byrnes, J., Caesar, S., Clee, C., Coffey, A., Connell, J., Cooper, J., Dominiczak, A., Downes, K., Drummond, H., Dudakia, D., Dunham, A., Ebbs, B., Eccles, D., Edkins, S., Edwards, C., Elliot, A., Emery, P., Evans, D., Evans, G., Eyre, S., Farmer, A., Nicol Ferrier, I., Feuk, L., Fitzgerald, T., Flynn, E., Forbes, A., Forty, L., Franklyn, J., Freathy, R., Gibbs, P., Gilbert, P., Gokumen, O., Gordon-Smith, K., Gray, E., Green, E., Groves, C., Grozeva, D., Gwilliam, R., Hall, A., Hammond, N., Hardy, M., Harrison, P., Hassanali, N., Hebaishi, H., Hines, S., Hinks, A., Hitman, G., Hocking, L., Howard, E., Howard, P., Howson, J., Hughes, D., Hunt, S., Isaacs, J., Jain, M., Jewell, D., Johnson, T., Jolley, J., Jones, I., Jones, L., Kirov, G., Langford, C., Lango-Allen, H., Mark Lathrop, G., Lee, J., Lee, K., Lees, C., Lewis, K., Lindgren, C., Maisuria-Armer, M., Maller, J., Mansfield, J., Martin, P., Massey, D., McArdle, W., McGuffin, P., McLay, K., Mentzer, A., Mimmack, M., Morgan, A., Morris, A., Mowat, C., Myers, S., Newman, W., Nimmo, E., O’Donovan, M., Onipinla, A., Onyiah, I., Ovington, N., Owen, M., Palin, K., Parnell, K., Pernet, D., Perry, J., Phillips, A., Pinto, D., Prescott, N., Prokopenko, I., Quail, M., Rafelt, S., Rayner, N., Redon, R., Reid, D., Renwick, A., Ring, S., Robertson, N., Russell, E., St Clair, D., Sambrook, J., Sanderson, J., Schuilenburg, H., Scott, C., Scott, R., Seal, S., Shaw-Hawkins, S., Shields, B., Simmonds, M., Smyth, D., Somaskantharajah, E., Spanova, K., Steer, S., Stephens, J., Stevens, H., Stone, M., Su, Z., Symmons, D., Thompson, J., Thomson, W., Travers, M., Turnbull, C., Valsesia, A., Walker, M., Walker, N., Wallace, C., Warren-Perry, M., Watkins, N., Webster, J., Weedon, M., Wilson, A., Woodburn, M., Wordsworth, B., Young, A., Zeggini, E., Carter, N., Frayling, T., Lee, C., McVean, G., Munroe, P., Palotie, A., Sawcer, S., Scherer, S., Strachan, D., Tyler-Smith, C., Brown, M., Burton, P., Caulfield, M., Compston, A., Farrall, M., Gough, S., Hall, A., Hattersley, A., Hill, A., Mathew, C., Pembrey, M., Satsangi, J., Stratton, M., Worthington, J., Deloukas, P., Duncanson, A., Kwiatkowski, D., McCarthy, M., Ouwehand, W., Parkes, M., Rahman, N., Todd, J., Samani, N., & Donnelly, P. (2010). Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls Nature, 464 (7289), 713-720 DOI: 10.1038/nature08979

Cleveland, L., & Grimstone, A. (1964). The Fine Structure of the Flagellate Mixotricha paradoxa and Its Associated Micro-Organisms Proceedings of the Royal Society of London. Series B, Biological Sciences (1934-1990), 159 (977), 668-686 DOI: 10.1098/rspb.1964.0025

Koretke KK, Lupas AN, Warren PV, Rosenberg M, & Brown JR (2000). Evolution of two-component signal transduction. Molecular biology and evolution, 17 (12), 1956-70 PMID: 11110912

Zhang, Q., Raoof, M., Chen, Y., Sumi, Y., Sursal, T., Junger, W., Brohi, K., Itagaki, K., & Hauser, C. (2010). Circulating mitochondrial DAMPs cause inflammatory responses to injury Nature, 464 (7285), 104-107 DOI: 10.1038/nature08780

Kilian, K., Bugarija, B., Lahn, B., & Mrksich, M. (2010). Geometric cues for directing the differentiation of mesenchymal stem cells Proceedings of the National Academy of Sciences, 107 (11), 4872-4877 DOI: 10.1073/pnas.0903269107

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Dominant transposases, becoming famous for your lab mistakes and more, in my Picks of the Week from RB.

Another week has gone by and some very interesting molbio blog posts have been aggregated to Researchblogging.org. Every week [see my opening post on the matter], I'll select some blog posts I consider particularly interesting in the field of molecular biology [see here to get a sense of the criteria that will be used], briefly describe them and list them here for you to check out.

Note that I'm only taking into consideration the molbio-related blog posts aggregated under "Biology".

Congratulations to everyone who got their post selected.

Transposable elements can greatly influence the structure and dynamics of the genomes they populate. Class 2 transposable elements or DNA transposons, are mobile genetic units that move using a single or double-stranded DNA intermediate. Moselio Schaechter at Small Things Considered comments on a recent Nucleic Acids Research paper reporting that transposases, enzymes involved in the movement of these genetic units, appear to be the most prevalent and abundant set of genes in nature (or at least in our genomic databases).

Everyone has made mistakes at the lab. In fact, you can check hundreds of them in Twitter under #scienceconfessions or #scifubar. Setting things on fire and throwing nasty solutions down the sink are part of the history of every lab. But what if a particular “mistake” turns out to have a tremendous influence on your field? Michele Arduengo at Promega Connections talks about “Sloppy Technicians and the Progress of Science” using the history of Hela cells and cytogenetics as an example.

(Image credit)

In addition to these posts, this week I’m launching “honorable mentions” for Picks of the Week. Posts under this category will only be linked to and quoted, but not summarized.

This week’s honorable mention goes to Lucas Brouwers at Thoughtomics, for his post entitled “On the Origin of Animals”.

“In a Nature paper published last month, a team of researchers used the conserved expression of microRNAs to piece together some information about a great-great grandmother of animals”

That's it for this week. Stay tuned for more MolBio Research Highlights!

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Some of the articles discussed in this week's selected posts:

Aziz RK, Breitbart M, & Edwards RA (2010). Transposases are the most abundant, most ubiquitous genes in nature. Nucleic acids research PMID: 20215432

Christodoulou, F., Raible, F., Tomer, R., Simakov, O., Trachana, K., Klaus, S., Snyman, H., Hannon, G., Bork, P., & Arendt, D. (2010). Ancient animal microRNAs and the evolution of tissue identity Nature, 463 (7284), 1084-1088 DOI: 10.1038/nature08744

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Surveying the gut microbiota, cross dressing chickens and more, in my Picks of the Week, from RB

Another week has gone by and some very interesting molbio blog posts have been aggregated to Researchblogging.org. Every week [see my opening post on the matter], I'll select some blog posts I consider particularly interesting in the field of molecular biology [see here to get a sense of the criteria that will be used], briefly describe them and list them here for you to check out.

Note that I'm only taking into consideration the molbio-related blog posts aggregated under "Biology".

Congratulations to everyone who got their post selected.

It has been estimated that the number of microorganisms in our body exceeds the number of human cells by a factor of ~10. The vast majority of these microbes reside in our gut. With the ultimate goal of “understanding and exploiting the impact of the gut microbes on human health and well-being” and to get a broader overview of the human gut microbial genes, a huge Illumina-based metagenomic approach has recently been published in Nature, reporting “3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals”.

Geek! discusses some of the fascinating results derived from this study.

(Image source)

This huge microbial community has a profound influence on our metabolism and nutrition and its alteration may be associated with a number of diseases. Tim Sampson at The Times Microbial discusses a fascinating new article reporting that mice deficient in Toll-like Receptor 5 (a component of the innate immune system expressed in the gut mucosa), develop “hallmark features of metabolic syndrome, including hyperlipidemia, hypertension, insulin resistance, and increased adiposity”. Notably, these alterations are correlated with changes in the composition of the gut microbiota and… (wait for it…)

“transfer of the gut microbiota from TLR5-deficient mice to wild-type germ-free mice conferred many features of metabolic syndrome to the recipients”.

How cool is that?

OK, enough with microorganisms. GrrlScientist at Living the Scientific Life (Scientist, Interrupted), brings us a fascinating post discussing in detail a recent article in which the authors examined three lateral gynandromorph chickens (a rare, naturally occurring phenomenon in which one side of the animal appears male and the other female -see image-) to investigate the sex-determining mechanism in birds. It seems that the underlying mechanism differs greatly from its mammalian counterpart.

Image of gynandromorph bird (Image credit)

And for the grand finale, human genomics!

Daniel MacArthur at Genetic Future comments on two recent papers representing the first ever studies to “employ whole-genome sequencing for disease gene discovery”.

Daniel comments on the importance of these papers for clinical genetics, but also raises an interesting issue regarding personal genomics:

“The key message here is that sequencing technology is still moving far faster than our ability to interpret the resulting data.”

That's it for this week. Stay tuned for more MolBio Research Highlights!

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Some of the articles discussed in this week's selected posts:

Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., Yamada, T., Mende, D., Li, J., Xu, J., Li, S., Li, D., Cao, J., Wang, B., Liang, H., Zheng, H., Xie, Y., Tap, J., Lepage, P., Bertalan, M., Batto, J., Hansen, T., Le Paslier, D., Linneberg, A., Nielsen, H., Pelletier, E., Renault, P., Sicheritz-Ponten, T., Turner, K., Zhu, H., Yu, C., Li, S., Jian, M., Zhou, Y., Li, Y., Zhang, X., Li, S., Qin, N., Yang, H., Wang, J., Brunak, S., Doré, J., Guarner, F., Kristiansen, K., Pedersen, O., Parkhill, J., Weissenbach, J., Antolin, M., Artiguenave, F., Blottiere, H., Borruel, N., Bruls, T., Casellas, F., Chervaux, C., Cultrone, A., Delorme, C., Denariaz, G., Dervyn, R., Forte, M., Friss, C., van de Guchte, M., Guedon, E., Haimet, F., Jamet, A., Juste, C., Kaci, G., Kleerebezem, M., Knol, J., Kristensen, M., Layec, S., Le Roux, K., Leclerc, M., Maguin, E., Melo Minardi, R., Oozeer, R., Rescigno, M., Sanchez, N., Tims, S., Torrejon, T., Varela, E., de Vos, W., Winogradsky, Y., Zoetendal, E., Bork, P., Ehrlich, S., & Wang, J. (2010). A human gut microbial gene catalogue established by metagenomic sequencing Nature, 464 (7285), 59-65 DOI: 10.1038/nature08821

Vijay-Kumar, M., Aitken, J., Carvalho, F., Cullender, T., Mwangi, S., Srinivasan, S., Sitaraman, S., Knight, R., Ley, R., & Gewirtz, A. (2010). Metabolic Syndrome and Altered Gut Microbiota in Mice Lacking Toll-Like Receptor 5 Science DOI: 10.1126/science.1179721

Zhao, D., McBride, D., Nandi, S., McQueen, H., McGrew, M., Hocking, P., Lewis, P., Sang, H., & Clinton, M. (2010). Somatic sex identity is cell autonomous in the chicken Nature, 464 (7286), 237-242 DOI: 10.1038/nature08852

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Non-inherited antibiotic resistance, jumping viruses and more, in my Picks of the Week from RB

Another week has gone by and some very interesting molbio blog posts have been aggregated to Researchblogging.org. Every week [see my opening post on the matter], I'll select some blog posts I consider particularly interesting in the field of molecular biology [see here to get a sense of the criteria that will be used], briefly describe them and list them here for you to check out.

Note that I'm only taking into consideration the molbio-related blog posts aggregated under "Biology".

Congratulations to everyone who got their post selected.

1) As I’ve stated before, the different steps in gene expression are stochastic biochemical events and this randomness can lead to substantial cell-to-cell variability in RNA and protein levels and have phenotypic consequences even within a clonal population of cells. Tim Sampson over at "The Times Microbial” brings us the second part of his 2-part series on “Noisy and Bistable Gene Expression” now commenting on the observation of “non inherited antibiotic resistance”.

2) Just how tough is to survive on Mars? Greg Fish at Weird Things discusses a recent article in which the Martian environment was simulated to perform experiments with different bacterial strains and concludes that:

Mars is not necessarily the most hostile place to life as we know it, but only when we’re talking about its unexplored underground world.

3) In some (few) cases, viruses are able to cross the species barrier effectively and cause disease. In fact, “this is one of the ways that ‘emerging infections’ get started”. Ian York at Mystery Rays from Outer Space comments on a paper suggesting several recent host shifts among members of the genus Ranavirus, major viral pathogens of cold-blooded vertebrates.

Frogs: A Chorus of Colors (Image source)

4) Last week, I selected a post by Lucas Brouwers in which he discussed an interesting paper reporting the use of protein transport machines in mitochondria as a model system to study how sophisticated molecular machines can evolve from simpler components [See Molecular machines and memorable African genomes in my Picks of the Week from RB]. As a sort of sister post to that one, LabRat now discusses the evolution of the import mechanism in chloroplasts.

From the post:

The only thing that seems clear is that like the mitochondrial import system, this was clearly pulled together from bits of old machinery lying around.

That's it for this week. Stay tuned for more MolBio Research Highlights!

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Some of the articles discussed in this week's selected posts:

Balaban NQ, Merrin J, Chait R, Kowalik L, & Leibler S (2004). Bacterial persistence as a phenotypic switch. Science (New York, N.Y.), 305 (5690), 1622-5 PMID: 15308767

Jancovich, J., Bremont, M., Touchman, J., & Jacobs, B. (2009). Evidence for Multiple Recent Host Species Shifts among the Ranaviruses (Family Iridoviridae) Journal of Virology, 84 (6), 2636-2647 DOI: 10.1128/JVI.01991-09

Gross J, & Bhattacharya D (2009). Revaluating the evolution of the Toc and Tic protein translocons. Trends in plant science, 14 (1), 13-20 PMID: 19042148

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Molecular machines and memorable African genomes in my Picks of the Week from RB

Another week has gone by and some very interesting molbio blog posts have been aggregated to Researchblogging.org. Every week [see my opening post on the matter], I'll select some blog posts I consider particularly interesting in the field of molecular biology [see here to get a sense of the criteria that will be used], briefly describe them and list them here for you to check out.

Note that I'm only taking into consideration the molbio-related blog posts aggregated under "Biology".

Congratulations to everyone who got their post selected.

1) Molecular machines participate in several biological processes and their evolution is a fascinating and fundamental question. The mitochondria, organelle derived from an α-proteobacterial endosymbiont, relies on such assemblies for correct functioning. For example, many genes coding for important mitochondrial proteins have been transferred to the nuclear genome and are synthesized in the cytoplasm: the importing of these proteins into this organelle is mediated by the action of the 4 membrane-embedded molecular machines.

(…) how could these molecular import machines evolve? No bacteria have protein complexes that import proteins over their double membrane, so where did these complexes come from and how did they acquire the functionality that they have now? (From the selected post)

Lucas Brouwers at Thoughtomics discusses an interesting paper reporting the use of protein transport machines in mitochondria as a model system to study how sophisticated molecular machines can evolve from simpler components.

From the paper:

We proposed that simple “core” machines were established in the first eukaryotes by drawing on pre-existing bacterial proteins that had previously provided distinct functions.

2) The genomes of an indigenous hunter-gatherer from the Kalahari Desert and a Bantu from southern Africa have recently been reported.

Modern humans arose in Africa about 250 000 years ago and only spread out to Europe and the rest of the world in the last 60 000 years, displacing Homo erectus in the process. The migrants that founded the modern European, Asian and American populations would have carried with them only fraction of humanity's genetic diversity when they left Africa but until recently genomics has focused on those populations. (from the selected post)

The indigenous hunter-gatherer people of southern Africa represent one of the oldest known lineages of modern humans. The genetic structure of these individuals, then, is important for understanding human diversity. David at The Atavism comments on the article and its implications.

Archbishop Desmond Tutu, the Bantu individual selected (Image source)

That's it for this week. Stay tuned for more MolBio Research Highlights!

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Some of the articles discussed in this week's selected posts:

Clements, A., Bursac, D., Gatsos, X., Perry, A., Civciristov, S., Celik, N., Likic, V., Poggio, S., Jacobs-Wagner, C., Strugnell, R., & Lithgow, T. (2009). The reducible complexity of a mitochondrial molecular machine Proceedings of the National Academy of Sciences, 106 (37), 15791-15795 DOI: 10.1073/pnas.0908264106

Schuster SC, Miller W, Ratan A, Tomsho LP, Giardine B, Kasson LR, Harris RS, Petersen DC, Zhao F, Qi J, Alkan C, Kidd JM, Sun Y, Drautz DI, Bouffard P, Muzny DM, Reid JG, Nazareth LV, Wang Q, Burhans R, Riemer C, Wittekindt NE, Moorjani P, Tindall EA, Danko CG, Teo WS, Buboltz AM, Zhang Z, Ma Q, Oosthuysen A, Steenkamp AW, Oostuisen H, Venter P, Gajewski J, Zhang Y, Pugh BF, Makova KD, Nekrutenko A, Mardis ER, Patterson N, Pringle TH, Chiaromonte F, Mullikin JC, Eichler EE, Hardison RC, Gibbs RA, Harkins TT, & Hayes VM (2010). Complete Khoisan and Bantu genomes from southern Africa. Nature, 463 (7283), 943-7 PMID: 20164927

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The Almighty Fungi: The Revolutionary Neurospora crassa

On January 11 2010, a new series of blog posts was born over at Benchfly: BenchFly’s Model Organism Week. The idea was to invite fellow science bloggers to discuss and present some of the many model organism used in biology to the rest of the science blogosphere.

In that post, a poll was displayed asking people´s model organism of choice, and offered the following alternatives:

* Mice
* Flies
* Rats
* Worms
* Zebrafish
* Primates
* Other

Immediately, and still in shock, I posted a comment asking the evident: where´s fungi??

This is what I wrote:

No fungi among the alternatives ?! I'm betting a good part of that "Other" percentage corresponds to fungi researchers

A few hours later, I was DMed through Twitter (to be DMed, refers to receiving a Direct Message -private conversation- through Twitter). Alan Marnett, Benchfly´s founder, invited me to write a post on "the fungi" for this series, to which I replied that "the fungi" is too vast for such a post and suggested focusing on particular fungi model organisms. Indeed, on Monday Benchfly featured a post on Saccharomyces cerevisiae, which as you know, we love! [ See An alternative cloning strategy: yeast recombinational cloning and Fourth time is the charm: the quest for the final plasmid].

So today, my post on a fascinating fungus (the model organism of choice in my lab) is up over at Benchfly. Here's the opening paragraph:

“This brief paper, revolutionary in both its methods and its findings, changed the genetic landscape for all time”.

This is how Norman Horowitz started a historical account celebrating the 50th anniversary of the landmark paper by Beadle and Tatum, published in 1941(Horowitz 1991). This work with the filamentous ascomycete fungus Neurospora (Beadle and Tatum 1941), started off a series of important breakthroughs that brought the fields of biochemistry and genetics together and initiated a revolution: the explosive development of biochemical genetics and molecular biology. Undeniably, the one-to-one relationship between genes and enzymes (the “one gene, one enzyme” hypothesis), a concept derived from this and follow-up work, had a tremendous impact on biology.

(continue reading)


So go visit Benchfly and read all about the contributions this fascinating fungus, Neurospora crassa, has made to the advancement of modern molecular biology. It will be a great and informative read on this classic model organism.

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Some of the references discussed in the main article:

Perkins DD (1992). Neurospora: the organism behind the molecular revolution. Genetics, 130 (4), 687-701 PMID: 1582553

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GWAS under attack?, historical evolutionary constraints, and a lot more, in my picks of the week from RB

Another week has gone by and some very interesting molbio blog posts have been aggregated to Researchblogging.org. Every week [see my opening post on the matter], I'll select some blog posts I consider particularly interesting in the field of molecular biology [see here to get a sense of the criteria that will be used], briefly describe them and list them here for you to check out.

This week's Picks encompass posts from both last week and the week before, as last week no Picks were posted. Also, this will be the last "Picks of the Week" till March (written by me), as I'm sort of going on vacation (at the very least, I'm going to take some time off from the lab).

Note that I'm only taking into consideration the molbio-related blog posts aggregated under "Biology".

Congratulations to everyone who got their post selected.

1) Drug-induced side effects resulting from secondary targets are an important limitation in drug development. Indeed, “one third of potential therapeutic compounds fail in clinical trials or are later removed from the market due to unacceptable side effects often caused by off-target binding”.
Sometimes, however, a compound binding multiple targets or sites (“polypharmacology”) can be an advantage: a single drug could be used for the treatment of two or three different diseases. Also,

The rational design of drugs that act via polypharmacological mechanisms can produce compounds that exhibit increased therapeutic potency and against which resistance is less likely to develop

Thus, having a way to predict and identify secondary targets of known molecules, is something useful. Iddo Friedberg at Byte Size Biology discusses a recent paper published in PLoS Computational Biology reporting:

a multidimensional strategy for the identification of secondary targets of known small-molecule inhibitors in the absence of global structural and sequence homology with the primary target protein.

Using this approach, the authors predicted a few secondary targets for a compound that inhibits a protein responsible for RNA processing in Trypanosoma brucei and validated some of them.

2) The early atmosphere, the one who witnessed the origin of life, differs greatly from the one present today, the former probably being characterized by very little oxygen and an abundance of carbon dioxide.
The rise of atmospheric oxygen, as stated by Sessions et al., “was an epic event for both the biosphere and geosphere, and paved the way for the evolution of animal life” [Current Biology, 19:R567-R574].

LabRat describes the atmospheric scenery where this marvellous phenomenon took place, billions of years ago, and speculates on the time it took multicellularity to arise from the “blob phase”.

3) After some hard and arduous work, Psi Wavefunction at Skeptic Wonder, a blogger who usually surprises us with fantastic stories from the bizarre and ever-surprising world of protists, now unveils her very own tree of Eukaryotes based on an impressive body of work. You should definitely check it out!

From the post, here’s one of the blogger’s reasons for composing this tree…

Remember how I often refer to the Keeling et al 2005 tree when pointing out where some obscure organism lies on the 'map'? Well, that tree is 5 years out of date now. In fields like molecular biology and genomics, a lot can change in five years; compounded with how the protistan phylogeny was still in murky, squishy swamp of a mess only about 10-15 years ago, the current tree is far from static.

4) A recent study using two vertebrate species (zebrafish and mouse), suggests that genes expressed early during development have a more dramatic effect when knocked out or mutated, and also are more likely to revert to single copy after whole genome duplication, than genes expressed late.

It then appears that constraints are high in early stages of vertebrate development, and that the timing of expression during development, constrains a gene’s "evolvability”

Lucas Brouwers at Thoughtomics comments on a recent paper addressing the following question: are these developmental and genomic constraints associated to the age of origin of the corresponding genes?

5) There has been a lot of fuzz regarding a new paper published in PLoS Biology recently that, according to “various articles around the internet”, supposedly undermines GWAS studies. But does it really?

The only real solid claim in the paper is that, if you do not include rare SNPs in your genome-wide association study, and rare SNPs of large effect are contributing to disease, then you will sometimes pick up more common SNPs as associated, because they are in Linkage Disequilibrium with the rare SNPs.
[…]
The paper makes no attempt to say whether this IS happening, just says that it CAN happen, and that we should be AWARE of it.

Luke Jostins at Genetic Interference takes a critical stand against this paper and makes some interesting points, particularly in the comments section.

I have a lot of issues with this paper, but I will be brief and stick to my main objection; the authors attempt to demonstrate that common associations can be caused by sets of rare variants, and in doing so inadvertantly show they most of them are not.[my emphasis]

That's it for this week. Stay tuned for more MolBio Research Highlights!

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Some of the articles discussed in this week's selected posts:

Durrant, J., Amaro, R., Xie, L., Urbaniak, M., Ferguson, M., Haapalainen, A., Chen, Z., Di Guilmi, A., Wunder, F., Bourne, P., & McCammon, J. (2010). A Multidimensional Strategy to Detect Polypharmacological Targets in the Absence of Structural and Sequence Homology PLoS Computational Biology, 6 (1) DOI: 10.1371/journal.pcbi.1000648

Falkowski PG (2006). Evolution. Tracing oxygen's imprint on earth's metabolic evolution. Science (New York, N.Y.), 311 (5768), 1724-5 PMID: 16556831

KEELING, P., BURGER, G., DURNFORD, D., LANG, B., LEE, R., PEARLMAN, R., ROGER, A., & GRAY, M. (2005). The tree of eukaryotes Trends in Ecology & Evolution, 20 (12), 670-676 DOI: 10.1016/j.tree.2005.09.005

Milinkovitch, M., Helaers, R., & Tzika, A. (2009). Historical Constraints on Vertebrate Genome Evolution Genome Biology and Evolution, 2010, 13-18 DOI: 10.1093/gbe/evp052

Dickson, S., Wang, K., Krantz, I., Hakonarson, H., & Goldstein, D. (2010). Rare Variants Create Synthetic Genome-Wide Associations PLoS Biology, 8 (1) DOI: 10.1371/journal.pbio.1000294

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