Chromatin and Epigenetics: From Omics to Single Cells

As part of its mission to encourage engagement within the genetics community, PLOS Genetics is sponsoring a number of conferences and meetings this year. In order to raise awareness about these conferences and the researchers who attend them we are featuring a number of these conferences on Biologue.

At the Chromatin and Epigenetics Conference, which took place in Strasbourg, France, on the 14th and 15th of October, PLOS awarded a student travel award to Paul Fields. Paul talks about his experiences at the conference, the topics discussed and the beauty of Strasbourg.

Few conferences are able to blend the beauty and history of old Europe with cutting-edge science from around the world, but that is exactly what Abcam achieved with their “Chromatin and Epigenetics: From Omics to Single Cells” meeting in Strasbourg, France.  Robert Schneider and Maria Elena Torres-Padilla put together a fantastic lineup of speakers from all over Europe and the United States, creating a very exciting meeting with highly relevant topics.  While the conference was aptly titled “From Omics to Single Cells”, it could just as easily have been called Omics AND Single Cells.  It was clear from early on that a common theme throughout the conference would be the integration of these two concepts to produce insights into the nature of chromatin and epigenetic regulation and how this contributes to cell state regulation.


The picturesque cathedral in the center of Strasbourg. Image credit: Paul Fields

I got into Strasbourg the night before the conference and was only able to see a little of the beauty of the town before the start.  I managed to sneak in some of the wonders of Strasbourg over the few days I was here, including the picturesque cathedral in the center of town.  Day one of the conference was loosely centered on the omics perspective, including a variety of new methods to identify and characterize DNA methylation and its various intermediates.  Already in the second talk of the conference Sebastian Smallwood blended the omics and the single cell, presenting a fascinating method to address single cell heterogeneity in DNA methylation using single cell bisulfite sequencing.  Another recurring theme of the first day, which would carry over into the second day, was understanding chromatin and chromosomal structures within the cell.  Both Wouter de Laat and Susan Gasser presented new insights into our understanding of the feedback between chromosomal positioning and silencing/heterochromatin using two very different systems and approaches.  The end of day one was headlined by keynote speaker John Gurdon, who presented new work into understanding why some cells resist the process of cellular reprogramming.  Along with this he demonstrated just how far and how rapidly our understanding of cellular regulation from a chromatin perspective has come.   The day finished up with a fantastic French dinner; lots of food and a surplus of wine, as well as great conversations about the topics of the day.


The conference venue: the Institute of Genetics and Molecular and Cellular Biology in Strasbourg, France. Image credit: Paul Fields

Day two began, as people straggled in after a long night of dancing, with the focus shifting towards single cells.  Bas van Steensel led off the day.  He was probably one of the most cited speakers of the conference, for his pioneering work into understand nuclear lamin interactions.  He has now pushed our understanding of nuclear lamin interactions to the single cell level.  Following in the vein of creative approaches, many of the speakers across the day presented new adaptations of old methodologies to address questions at a single cell level.  As Alex van Oudenaarden said, just because you don’t think it will work, doesn’t mean it’s not worth trying. His group was able to adapt TriZOL-based methods to generate single cell RNA-sequencing.  From that approach they could then try to identify rare cell types, integrating both novel sequencing methods as well as new approaches to computationally handle outliers.  One of the more humorous moments of the day was Peter Fraser’s analogy for why we need to study single cells, comparing a panel of Wayne Rooney’s various expressions to a population of cells. If averaged across, only the most defining features stand out, his ears, ignoring the intricacies of the individual moments.  Tony Kouzarides was the second keynote speaker. His long ties to both Robert Schneider and Maria Elena Torres-Padilla provided humorous introductions and his body of work has dramatically broadened our understanding of chromatin mechanisms.  Furthering the topic of taking both omics and single cell readouts to a functional level, Brad Bernstein proved an appropriate final speaker, as his work on both histone modifications and single cell analysis of transcription across cancers provides a model for how this work can be used therapeutically to treat patients.

One of the great things about getting so many fascinating speakers into one conference is it becomes easy to see how researchers continue to feed off of each other, and in turn benefit from a wide range of expertise.  Across the speakers (and also in the posters) at this conference, approaches ranged from genetic to biochemical to biophysical and everywhere in between, yet all having a similar goal to better understand the mechanisms of chromatin and epigenetics.  As the problems become more difficult it will take a host of new integrated approaches to continue to solve these questions and apply them outside of the lab.  In closing, I would like to thank Abcam and PLOS for the opportunity to experience this conference in person, and visit the beautiful city of Strasbourg.


Category: Biology, Community, Conference, Education, Epigenetics, Genetics, PLOS Genetics, Research | Leave a comment

Melanoma Cells: A Fatal Attraction to LPA

Credit: Flickr user Phil Whitehouse.

A beautiful day, but what’s happening under the surface? Credit: Flickr user Phil Whitehouse.

A hot day, blue sky and an even bluer sea. A perfect day to spend on the beach. But while our skin is sizzling, very few of us are aware of what some of our cells might be up to. Melanoma cells could be busy dividing and trying to escape the skin in search of a blood vessel through which to colonize other parts of our body. But how do they decide it’s time to migrate from the skin? Is there some sort of “go” signal that makes them leave their safe haven and cause havoc elsewhere?


Andrew Muinonen-Martin and researchers from the Beatson Institute at the University of Glasgow led by Robert Insall have been busy trying to find a way to stop this aggressive cancer spreading. In a new article just published in PLOS Biology, they tell us about a very promising breakthrough in their search for this “go” signal that could be disrupted to prevent metastasis of these tumors.


Why should we worry if we suddenly realize that we have a strange mole growing in our skin at an alarming pace? Melanocytes (a specialised skin cell) produce a pigment called melanin whenever we are exposed to sunlight – this is what gives us the highly desired tanned look. However these melanocytes aren’t born in the skin, but in a far-away developmental tissue called the neural crest; their long migration to the skin where they can protect us against UV light means that they’re naturally good ‘runners’.


Credit: doi:10.1371/journal.pbio.1001966

Credit: doi:10.1371/journal.pbio.1001966

As we well know, these guardians of our skin can occasionally turn nasty – when a dangerous mutation occurs that transform them in cancer cells, they start proliferating horizontally within the skin. This would be unpleasant if it remained confined to the skin, but then something happens that make these cells to migrate downwards instead until they manage to escape into the body. This is the dreaded phase of melanoma: within weeks these highly mobile cancer cells can spread all around the body, with disastrous and often lethal consequences.


Insall, Muinonen-Martin and colleagues focus their research on chemotaxis – chemical cues that attract and direct cells’ movements – and they set up to try to identify a potential signal that might be triggering the melanoma cells’ deadly migration. They tested the effect of several known chemoattractants by closely watching the migration of melanoma cells in direct-viewing chambers that they previously developed. They found that lysophosphatidic acid (LPA), a fatty chemical common in human tissues – and in the serum used in cell culture medium – was able to attract these cells particularly efficiently. But in order to attract cells, a chemoattractant needs to be present in the form of a gradient so that cells can move from a region with less of the chemical to areas where it is more abundant. How is a potential LPA gradient formed in these tumors?


Watch this video of melanoma cells swarming from an area of low LPA – on the left -  to an area of high LPA – on the right (credit: doi:10.1371/journal.pbio.1001966):


The team analyzed the culture medium from groups of melanoma cells with different densities and saw that the cells were effectively breaking down the LPA molecules nearest to them. The result is a self-generated LPA gradient; low where cells have grown a lot – for example a tumour – and high away from the tumour where there are no melanoma cells. The researchers then looked closely at the more realistic ‘in vivo’ scenario in real tumours from mutant mice that are susceptible to melanoma. They took biopsies from different areas around the tumour, and use mass spectrometry to measure LPA levels. Again, this revealed an outward gradient. Cells located close to the center of the tumour were exposed to low levels of LPA, whereas cells at the edges of the tumour had access to much higher levels. Inevitably, this gradient seems to attract melanoma cells out of the tumour, following the scent of LPA and blazing a trail outwards, perhaps to a handy blood vessel.


LPA - the fatal attractant.

LPA – the fatal attractant.

The conclusion is, therefore, that the melanoma generates the signal for its own metastasis. But the researchers’ identification of the bearer of this signal leaves a door open for hope. If we can manage to stop LPA gradients being generated in the tumor –perhaps by inhibiting the enzyme that breaks LPA down – metastasis of these cells might become preventable. In the meanwhile, while a ray of hope shines in the sky, make sure you and your skin stay well protected with sunscreen.
Muinonen-Martin, A., Susanto, O., Zhang, Q., Smethurst, E., Faller, W., Veltman, D., Kalna, G., Lindsay, C., Bennett, D., Sansom, O., Herd, R., Jones, R., Machesky, L., Wakelam, M., Knecht, D., & Insall, R. (2014). Melanoma Cells Break Down LPA to Establish Local Gradients That Drive Chemotactic Dispersal PLoS Biology, 12 (10) DOI: 10.1371/journal.pbio.1001966

Category: Biology, Cancer, Cell signalling, Developmental biology, Disease, PLOS Biology | Leave a comment

This week in PLOS Biology

In PLOS Biology this week, you can read about moving lipids around the cell, good and bad autophagyhow skin cancer metastasises, and mending DNA replication forks safely.


 Moving Lipids from Organelle to Organelle

Prinz thumbMoving lipids and proteins from the endoplasmic reticulum to the mitochondria (and vice versa) is a vital process, but the mechanism of transfer which occurs when regions of these organelles are in close contact is not known. Sujoy Lahiri, William Prinz and colleagues used a genetic screen in Saccharomyces cerevisiae yeast to identify mutants with defects in lipid exchange. They then reported that a protein complex called EMC present in the endoplasmic reticulum is important for tethering it to mitochondria. They propose that the EMC interacts with the mitochondrial outer membrane complex TOM, placing the two organelles in close apposition and aiding the transfer of lipids. Failure to do this results in cell death, showing that the process is essential for life.


Autophagy: Making Sense of a Double-Edged Sword

Autophagy is the mechanism by which cellular material is delivered to lysosomes and degraded. The extensive literature on this process brings us to the conclusion that sometimes it is good and sometimes it is bad. For example, there was a recent attempt to inhibit autophagy in a child with a brain tumour. So if we understood more about how autophagy impacts on health and disease, could we improve treatment and prevention? This is the question asked in a new Essay by Andrew Thorburn. He reviews our knowledge of autophagy and bacterial infection, cancer and cell death. He concludes that mechanistic understanding of biological processes will lead to practical applications, and that the current rapid pace of progress is encouraging.


Melanoma Cells: A Fatal Attraction for LPA

Credit: doi:10.1371/journal.pbio.1001966

Credit: doi:10.1371/journal.pbio.1001966

Melanoma is a highly metastatic and aggressive form of cancer. In a fascinating new study, Andrew Muinonen-Martin, Robert Insall and colleagues address what drives melanoma cells to start migrating out from the tumour – a poorly understood process. They focussed on the chemical signals that guide tumour cell migration. In both cell lines and in mice, they showed the importance of the breakdown of a lipid called lysophosphatidic acid (LPA). A gradient is created, with higher concentrations of LPA further away from the tumour, which acts as a chemoattractant, drawing tumour cells out into surrounding skin and blood vessels. These findings could have important implications for new treatment avenues for skin cancer. Read more in this blog post by Ines Alvarez-Garcia.


Reining in the Copy-Editors

Maintaining genetic fidelity is of paramount importance to living organisms. During DNA replication, obstacles to the progression of DNA replication forks can trigger repair by patching in the correct DNA sequence, using the second copy of that chromosome as a template – a process known as homologous recombination. However, use of the wrong template can result in genome rearrangements, such as those often observed in cancer and genomic disorders. Violena Pietrobon, Sarah Lambert and colleagues investigated how the delicate balance between insufficient and excessive homologous recombination is maintained, identifying an evolutionarily conserved interplay between CAF-1 (a chromatin assembly factor) and RecQ-type helicases that helps to maintain genome stability in the face of replication stress.


Category: Biology, Cancer, Cell biology, Cell signalling, Disease, Molecular biology, PLOS Biology | Leave a comment

Keep Calm and Evolve On

Lauren Richardson, Associate Editor for PLOS Biology, discusses a new paper published in the journal.

We generally think of evolution as a beneficial process, letting organisms adapt and excel in new and different environments. But as we all know, not all change is good. Deleterious mutations are common in natural populations, and often piggy-back on adaptive, beneficial mutations. When a harmful mutation crops up in the genome, restricting or altering an organism’s ability to function well, evolution must respond to restore the ideal condition. The main way this is done is through compensatory evolution, where the effects of detrimental mutations are compensated by other mutations elsewhere in the genome. In a recent study published in PLOS Biology, a group based in Szeged, Hungary, led by Csaba Pal, characterized – on a massive scale – how compensatory evolution is able to restore peace and harmony after a disruptive genomic event, gene loss.

Image Credit: Sarah Bissonnette.

Image Credit: Sarah Bissonnette.

Saccharomyces cerevisiae (baker’s yeast), in lab conditions, likes to double every one-and-a-half hours. You could practically set your watch to a happily growing culture. Deletion of certain genes, however, will slow yeast’s growth rate. Slow growth is a highly unfavorable state for a yeast, as it’s in direct competition with neighboring yeasts in a culture (or on a rotting apple). Slower growth means a higher chance of getting swamped out of a population. To combat this, compensatory evolution leads to additional mutations in the genome to restore fitness. But how does this process work?

Image Credit: Csaba Pal

Image Credit: Csaba Pal

Using the awesome power of yeast genetics, the authors characterized 180 slow-growing yeast strains, each one missing a single gene. Amazingly, they found that nearly 70% of the strains were able to improve their growth rate following laboratory evolution experiments. The authors grew the yeast for 400 generations, which, if these yeasts were humans with a 20-year generation time, would be roughly equivalent to 8000 years! The 180 missing genes covered a wide range of molecular processes, showing that evolution can solve almost any kind of genetic problem.

The authors did their studies in quadruplicate, meaning that for each gene deletion they grew four independent cultures. By sequencing the genomes of evolved strains, they found that, in general, each independent culture used different compensatory mutations to fix the same slow-growth problem. Interestingly, by comparing gene expression profiles, they found that the compensatory fix never restored the original state. Instead the yeast found new ways to regain optimal growth – a workaround instead of a faithful restoration. The effects of these diverse fixes were revealed when they grew the evolved strains in various stressful conditions – each independently evolved strain responded differently. This demonstrates how gene loss can “drive populations to new adaptive peaks,” and can make them potentially better or worse suited to a new environment.

And because all biological studies can be tied in to cancer biology (see anyone applying for postdoctoral funding), I should mention that gene loss events are frequent during tumorigenesis. From these studies you could hypothesize that a gene loss event early on in tumorigenesis could drive compensatory mutations that might promote an increased growth rate and adaptation to the completely crazy tumor microenvironment. But to yeast geneticists, their first thought is probably: what does this mean for the knock-out collections? It means you should probably freeze them down. FAST.

Szamecz, B., Boross, G., Kalapis, D., Kovács, K., Fekete, G., Farkas, Z., Lázár, V., Hrtyan, M., Kemmeren, P., Groot Koerkamp, M., Rutkai, E., Holstege, F., Papp, B., & Pál, C. (2014). The Genomic Landscape of Compensatory Evolution PLoS Biology, 12 (8) DOI: 10.1371/journal.pbio.1001935

Category: Biology, Blog, Genetics, PLOS Biology | Tagged , , , | 1 Comment

Pupil size and decision making, timing evolutionary innovation and understanding ATP allosteric functions: the PLOS Comp Biol September issue

Here’s our pick of the highlights from September’s PLOS Computational Biology.

The precision with which people make decisions can be predicted by measuring pupil size before they are presented with any information about the decision. According to Peter Murphy and colleagues, spontaneous, moment-to-moment fluctuations in pupil size can predict how a selection of participants varied in their successful decision making. A larger pupil size indicated poorer upcoming task performance, due to more variability in the decisions made once the relevant information was presented. The authors also found that certain individuals who had the largest pupils overall also tended to be the least consistent in their decisions.

Our September issue image: Matching drug binding pockets in protein models using sequence order-independent structure alignments. Image Credit: Michal Brylinski.

Our September issue image: Matching drug binding pockets in protein models using sequence order-independent structure alignments. Image Credit: Michal Brylinski.

Evolutionary adaptation can be described as a biased, stochastic walk of a population of sequences in a high dimensional sequence space. The population explores a fitness landscape and the mutation-selection process biases the population towards regions of higher fitness. Krishnendu Chatterjee and colleagues estimate the time scale that is needed for evolutionary innovation, using the length of the genetic sequence that needs to be adapted as their key parameter. The authors show that a variety of evolutionary processes take exponential time in sequence length, and propose a specific process, ‘regeneration processes’, which allows evolution to work on polynomial time scales. In this view, evolution can solve a problem efficiently if it has solved a similar problem already.

Endogenous adenosine-5’-triphosphate (ATP) can be regarded as a substrate and an allosteric modulator in cellular signal transduction. By analysing the properties of allosteric and substrate ATP-binding sites, Shaoyong Lu and colleagues found that the allosteric ATP-binding sites are less conserved than the substrate ATP-binding sites. Allosteric ATP molecules adopt both compact and extended conformations in the allosteric binding sites, while substrate ATP molecules adopt extended conformations in the substrate binding sites. The authors’ results provide an overall understanding of ATP allosteric functions responsible for regulation in biological systems.


Category: Computational biology, Evolution, Neuroscience, PLOS Computational Biology | Tagged , | Leave a comment

This week in PLOS Biology

In PLOS Biology this week, you can read about the notion of the “balance of nature“, female mate choice in fruit flies, and the role of heterochromatin in chromosome cohesion.


The “Balance of Nature”—Evolution of a Panchreston

Simberloff Flickr Paxson Woelber

Image credit: Flickr user Paxson Woelber

In this new perspective, Daniel Simberloff discusses the notion of a “balance of nature”. He takes us on a historical tour,  from the early Greeks – who believed balance was maintained by the gods (with aid from human and animal sacrifice) – via the interventionist God of the Middle Ages, to the delicate balance implied by Darwin, with constant emphasis on competition. Recent research, by contrast, recognises the term as somewhat defunct, and the more dynamic aspects of nature, punctuated with natural and human-induced disturbances, are emphasised. Yet the idea of a “balance” lives on in the popular imagination.


Sticky Chromosomes Get Stretched

The characteristic ‘X’ shape of chromosomes during cell division arises because the sister chromatids remain connected at the centromere, a region of the chromosome that contains long stretches of repetitive and physically compacted DNA called heterochromatin. A new study in PLOS Biology this week dissected the roles of heterochromatin and the centromeres in cohesion of sister chromatids. Raquel Oliveira, William Sullivan and colleagues tested fruit fly strains where stretches of heterochromatin were inappropriately inserted in chromosomal regions distant from the centromere. They found that this did cause increased cohesion (through greater loading of the clamp protein Cohesin), and therefore induced stretching of the chromosomes during cell division. This finding could be of some relevance to human cancers, where rearrangements involving heterochromatic regions often occur.


To Mate or not to Mate: How Female Flies Choose

Joseph Schinaman and Rui Sousa-Neves

Image credit: Joseph Schinaman and Rui Sousa-Neves

Although male courtship has been studied extensively in Drosophila, the neural basis for female receptivity remains unknown (see also this paper on a related topic). Joseph Moeller Schinaman, Rui Sousa-Neves and colleagues attempted to map some of the circuitry of female mate choice, exploiting a quirk of flies that have mutations in the gene encoding the transcription factor DATILÓGRAFO. The gene is named – in Portuguese – after the odd typist-like leg movements of the mutant flies, but the researchers also noticed that the female mutants had no interest in the males. They established that DATILÓGRAFO was required in three regions of the brain, including the olfactory lobe, for normal mating receptivity.

Category: Biology, Ecology, Epigenetics, Evolution, Genetics, Genomics, Neuroscience, PLOS Biology | Leave a comment

This Week in PLOS Biology

In PLOS Biology this week, you can read about social learning in chimps, how the central and peripheral nervous systems stay separate, how the bird wrist evolved, synchronising circadian clocks and a protein essential to the TFIIH complex.

Social Learning of Tool Use in Wild Chimpanzees

KB leaf sponge moss - Cat Hobaiter (1)

Image credit: Cat Hobaiter

Chimpanzees are widely considered as the most ‘‘cultural’’ of all non-human animals, despite the lack of direct evidence for the spread of novel behaviours through social learning in the wild. In their new paper, Catherine Hobaiter, Thibaud Gruber and colleagues developed new dynamic social network analyses to test the spread of two behaviours in a group of wild chimps in Budongo Forest, Uganda. These behaviours were ‘moss sponging’ (using moss to produce a sponge) and ‘leaf sponge re-use’ (using a sponge discarded by another individual). They found strong evidence for social transmission of moss sponging among this group of chimps.

See moss-sponging behaviour in chimps in these videos:


Separating Nervous Systems – it’s All in the Wrapper

Kucenas Cody J. Smith

Image credit: Cody J. Smith

The points where axons cross between the central and peripheral nervous systems (CNS and PNS) are known as transition zones, but the mechanisms that establish and maintain this precise segregation are unknown. Cody Smith, Sarah Kucenas and colleagues used in vivo time-lapse imaging in zebrafish to identify a novel cell type responsible for stopping CNS-residing glia from entering the PNS. They call these cells ‘motor exit point glia’. These results identify an aspect of peripheral nerve composition that may be pertinent in human health and disease.


How Dinosaur Arms Turned into Bird Wings

Since their emergence from early dinosaurs, birds have reduced the number of bones in their wrist, but the origins and identity of those remaining are hard to trace. Wrists went from straight to bent and hyperflexible, allowing birds to fold their wings neatly against their bodies when not flying. In their new paper in PLOS Biology, João Francisco Botelho, Alexander Vargas and colleagues draw on the fields of embryology and paleontology to resolve this puzzle. Their study integrates paleontological and developmental data (including immunostaining of embryos across a wide range of species) and clarifies the relationship between each of the four ossifications in birds and those found in non-avian dinosaurs. Read more in the accompanying Synopsis.


Synchronise Watches!

Circadian molecular clocks are essential for maintaining daily cycles in animal behaviour and we have a good understanding of how these clocks work in individual pacemaker neurons. However, the accuracy of these individual clocks is meaningless unless they are synchronized with one another. Ben Collins, Justin Blau and colleagues discovered that in the fruit fly Drosophila melanogaster, circadian pacemaker neurons are regulated by two synchronizing signals (the neuropeptide PDF and glutamate) that are released at opposite times of day, generating rhythmic changes in intracellular cyclic AMP.


XPD – Different Jobs in Repair and Transcription


Image credit: pbio.1001954

The multiprotein complex TFIIH is crucially involved in two fundamental cellular processes—the transcription of genes by RNA polymerase II and the repair of UV-damaged DNA by a mechanism called nucleotide excision repair (NER). A helicase enzyme called XPD is part of the TFIIH complex, but it’s unclear which properties of XPD are required for which of TFIIH’s two cellular roles. Jochen Kuper, Caroline Kisker and colleagues found that in DNA repair, this protein works as an enzyme, but for transcription it is merely required as a structural protein to hold TFIIH together.



Category: Biology, Cell biology, Cell signalling, Developmental biology, Evolution, Genetics, Molecular biology, Neuroscience, PLOS Biology | Leave a comment

Expanding the Homepages of Knowledge: the Topic Pages Collection in PLOS Computational Biology

Back in 2012 PLOS Computational Biology began an experiment that aimed to combine the prestige and rigorous peer review associated with publishing in a scientific journal and the dynamic nature and easily accessible language of Wikipedia. Over two years and six articles later, today sees the launch of PLOS Computational Biology’s Topic Pages Collection with the publication of the seventh Topic Page, “Multi-state Modeling of Biomolecules”.

Image Credit: PLOS

Image Credit: PLOS

Topic Pages aim to fill the gaps in current computational biology topics on Wikipedia. New submissions are drafted and undergo open peer review on a publically-viewable PLOS Wiki. Once a Topic Page is accepted, a static, citable version is published in PLOS Computational Biology and indexed in PubMed, while, under the guidance of one of the journal’s Topic Pages Editors, Daniel Mietchen, a living version of the document is uploaded to the corresponding Wikipedia article.

 “I was fascinated by the idea of spreading knowledge through Wikipedia and its cross linking capabilities, and thought that it was absolutely essential that experts in the field of computational biology and bioinformatics (as well as other fields) be more actively and widely involved in the process,”

says Topic Pages Editor Shoshana Wodak, who has overseen the review process for all seven articles.

“Having the Topics pages rigorously reviewed is a guarantee of quality, which Wikipedia contributions usually don’t have, and their concomitant publication in a respected journal offers authors the incentive to do the work. It also offered us the possibility of increasing the transparency and efficiency of the reviewing process, by allowing [and] encouraging reviewers to engage in a direct dialog with the authors.”

Melanie Stefan, an author on ‘ Multi-state modeling of biomolecules’, as well as the fifth Topic Page, ‘Cooperative Binding’, agrees:

“As scientists, it is our duty to pursue knowledge, but it is also our duty to share this knowledge with the world…I also like the fact that a Topic Page is less static than a traditional review article. Once it is published, it acquires a life of its own: People can add to it, amend it and alter it to reflect the latest developments in the field. This is a tremendously exciting process.”

For those considering a pre-submission inquiry to the collection, Spencer Bliven, Topic Page author and host of the PLOS Wiki has these words of advice:

“Learn to love the wiki environment. While the syntax can be a bit difficult at first, collaborating on a wiki page is much easier than trying to shuffle Word documents back and forth. I would also caution authors to avoid viewing the paper possessively, but to consider it a community project from the start. After publication, your Topic Page will most likely receive significant edits. This is a good thing, but it requires being a bit humble about your own writing skills.”

Finally, Topic Pages Editor Daniel Mietchen offered his thoughts on possible future paths the initiative could take:

“In principle, [the] direction [I would like to see] would be “higher, further, faster”: higher community engagement (e.g. through more Topic Pages, or more functionality, e.g. a prominent “Edit on Wikipedia” button, or links to Wikipedia from all PLOS abstracts), further journals (both within and beyond PLOS), and faster processes – even ignoring for a moment the problem of finding reviewers (which affects all journals, not just at PLOS), the publication process at PLOS (which is reasonably fast by industry standards) is very slow from a wiki (which means “quick”) perspective.

Another important direction to aim at would be to try to come closer to the workflows of researchers by publishing media files or data-related notes as Topic Pages tailored to Wikimedia Commons or Wikidata. The issue images at PLOS journals already go in this direction…”

With two more Topic Pages currently in peer review, the project is still looking for additional proposals; take a look at the author guidelines and get in touch at ploscompbiol[at] if you would like to be involved.

Category: Uncategorized | Leave a comment

This week in PLOS Biology

In PLOS Biology this week, you can read about a new mechanism for incomplete puberty and infertility, and the control of embryonic tissue separation by ephrin/Eph pairs.


Rab3α Scaffolding and the Control of Puberty

de Roux

Image credit: pbio.1001952

Brooke Tata, Lukas Huijbregts, Nicolas de Roux and colleagues have described a new genetic syndrome, observed in three brothers, involving a complex set of symptoms such as incomplete puberty and non-autoimmune diabetes. Genetic analyses of the family revealed that they suffered from deletion of 15 nucelotides from the DMXL2 gene. This gene encodes Rabconnectin-3α, a protein involved in scaffolding the regulators of small GTPase Rab3α intracellular trafficking (see also this recent PLOS Biology paper).  The authors found involvement for the protein in both GnRH secretion in the brain and insulin secretion in the pancreas – providing clues as to how decreased DMXL2 could be responsible for incomplete puberty and diabetes in this syndrome. Read more in the accompanying synopsis.


Embryonic Tissue Separation Depends on Specific Combinations of Ligand and Receptor Pairs

Image credit: pbio.1001952

Image credit: pbio.1001955

How embryonic tissues separate from each other to shape the developing organism is a fundamental question in developmental biology. In vertebrates, this process relies on local repulsive reactions specifically generated at contacts between cells of different types. We believe from recent evidence that the interaction is between surface proteins called ephrins and Eph receptors on the opposing groups of cells. However it’s been unclear how this repulsion is restricted to the tissue boundary and doesn’t take place within the tissues themselves. A new paper by Nazanin Rohani, Francois Fagotto and colleagues used a Xenopus model, and found that the concentration and binding affinities of specific ligand–receptor pairs largely explain the specificity of this key developmental program. Read more in the accompanying synopsis.


Category: Biology, Cell biology, Cell signalling, Developmental biology, Disease, Genetics, PLOS Biology | Leave a comment

This week in PLOS Biology

In PLOS Biology this week, you can read about plant extinction at the end of the Cretaceous, human tolerance to HIV and control of plant responses to hypoxia.


The End-Cretaceous Impact Winter Killed Off Slow-Growing Plants

Blonder striking imageFINAL

Image credit: Benjamin Blonder

Sixty-six million years ago the Chicxulub bolide impacted the Earth, marking the Cretaceous–Paleogene boundary. We all know about the association between this event and the extinction of the non-avian dinosaurs, but what about the plants? In a new research paper, Benjamin Blonder, Brian Enquist and colleagues have addressed the survival strategies of the plants (half of which went extinct at this time). Using >1000 fossil leaves, spanning a 2-million-year interval, they used leaf minor vein density and leaf mass per area as proxies for carbon assimilation and carbon investment. Their results supported the hypothesis that an impact winter would have selected against slow-growing evergreen species, a possible cause of the modern dominance of high-productivity deciduous angiosperm forests. Read more in the accompanying synopsis.

Human tolerance against HIV

Flickr NIAID

Image credit: NIAID

Roland Regoes and colleagues, in their new research article, have addressed the strategies of ‘tolerance’ and ‘resistance’ in humans, in the context of HIV. They asked used the Swiss HIV Cohort Study to ask if humans vary in their tolerance to HIV, and whether there is a genetic basis for tolerance. CD4+ T-cell increase was used as a proxy for tolerance, and viral load decline for resistance in a well-studied cohort of infected individuals. They found that tolerance and resistance had independent genetic origins and also that individuals who are heterozygous for the HLA-b immunity gene are more tolerant. Younger people were more tolerant to HIV infection. These findings add to our understanding of how hosts tolerate infections and could open new avenues for treating infections.

DNA Binding Protein Controls Plant Transcription when Oxygen is at a Premium

Plants need to be able to maintain respiration during hypoxic events, such as waterlogging of their roots during flooding. The main regulator of the response to these events has been identified as RAP2.12, which is produced under normal conditions, but then degraded. In hypoxic conditions this degradation stops. Now Beatrice Giuntoli, Pierdomenico Perata and colleagues have addressed the flipside of this: what prevents an inappropriately excessive hypoxic response? They found that the transcription factor HRA1 is needed, and creates a negative feedback loop with RAP2.12. The authors argue that this could have implications for breeding flood-resistant crops.

Category: Biology, Climate, Disease, Ecology, Environment, Evolution, Genetics, Infectious disease, Molecular biology, Plant biology, PLOS Biology, Research | Leave a comment