CHARMMing molecular simulations, midge swarms, and swimming C. elegans: the PLOS Computational Biology July 2014 Issue

This month’s issue saw the publication of three Education articles: Web Based Computational Education with CHARMMing. In Part I: Lessons and Tutorial, Miller et al. present their freely available, interactive, step-by-step guide for performing common molecular simulation tasks integrated into the CHARMM INterface and Graphics web user interface. Part II: Coarse Grained Protein Folding makes connections between modern molecular simulation techniques and topics commonly presented in advanced undergraduate lectures on physical chemistry, while Part III: Reduction Potentials of Electron Transfer Proteins is a module implemented in the CHARMMing web portal for fast determination of reduction potentials, , of redox-active proteins. These articles add a valuable resource on a widely used tool to our popular Education collection, and you can read a blog post about them written by Editor-in-Chief Ruth Nussinov and Guest Editor Qiang Cui here.

Image Credit: Federico Pedraja

Image Credit: Federico Pedraja

An intriguing paper from Attanasi et al. addresses the widespread biological phenomenon of collective behaviour, from cell colonies to flocks of birds. In Collective Behaviour without Collective Order in Wild Swarms of Midges the authors perform three dimensional tracking of large swarms of midges, finding that swarms display strong collective behaviour despite the absence of collective order. The findings of Attanasi et al. suggest that correlation, rather than order, is the true hallmark of collective behaviour in biological systems. We also recommend checking out the mesmerizing supplementary videos of the midge swarms in action.

Finally, a new Software article was added to the collection this month, CeleST: Computer Vision Software for Quantitative Analysis of C. elegans Swim Behavior Reveals Novel Features of Locomotion. Authors Restif et al. report on the first comprehensive computer vision software for analysis of the swimming locomotion of C. elegans. The CeleST software tracks swimming of multiple animals, measures 10 novel parameters of swim behaviour that can fully report dynamic changes in posture and speed, and generates data in several analysis formats, complete with statistics. The authors hope that CeleST will be “a powerful tool for a high-throughput, high-precision analysis of molecules, neuronal circuits, behavior, and plasticity to advance the effort toward understanding dynamic control of behaviour”.

Want to read more? Navigate to our newly-revamped journal homepage to find other articles from the July 2014 Issue.

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This week in PLOS Biology

In PLOS Biology this week you can read about cataloging microbial life,  how spider silk is made, a new class of Alzheimer’s drug and an insight into repairing nerve damage.

 

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Image credit: Tatyana Smirnova

A new Community Page, by Nikos C. Krypides and colleagues, calls for a more unified approach to cataloguing microbial life. This would consist of a comprehensive genomic catalogue of all cultured Bacteria and Archaea by sequencing the type strain of each species. The catalogue would be a great asset for the large-scale discovery of novel genes and functions and to mine microbial genomic data for uses such as combating antibiotic resistance.

 

 

Credit Anna Rising doi10.1371journal.pbio.1001922.g001

Image credit: Anna Rising

How exactly do spiders spin silk? We know that the main components of spider silk are ‘spidroin’ proteins, and we also know these are stored in soluble form and rapidly converted to a material stronger than steel as they leave the spider’s body. Now new research by Marlene Andersson, Anna Rising and colleagues gives some greater insight into this process. Using ion-selective microelectrodes in the silk glands of orb weaver spiders, they showed that a chemical pH gradient is maintained along the gland. Carbonic anhydrase was crucial to maintaining this gradient, and the authors propose a new ‘lock and trigger’ model for spider silk formation by pH-induced rearrangement of the spidroin structure. Read more in the accompanying synopsis.

 

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Image credit: pbio.1001924

A novel class of drug has been identified which could have potential for the treatment of Alzheimer’s disease and other neurodegenerative disorders. Researchers have been attempting to inhibit an enzyme called STEP (striatal-enriched protein tyrosine phosphatase) which is overactive in Alzheimer’s disease. In their new research article, Jian Xu, Paul Lombroso and colleagues report their serendipitous discovery of a new STEP inhibitor, which remarkably was elemental sulphur (S8), found as a contaminant in other drugs during a high throughput screen. After converting S8 to a more manageable form to use as a drug, the team tested it in cell culture and in a mouse model. The results were encouraging. See the accompanying synopsis.

 

Nerves rarely re-grow after severe spinal injury, potentially resulting in permanent paralysis. This is partly because of inhibitory signals which bind to the myelin Nogo receptor, which in turn bind co-receptors such as the protein p75. A research article by Marçal Vilar, Tsung-Chang Sung, and Kuo-Fen Lee sheds new light on the regulation of p75, which needs to dimerize to perform its function. They found that in mice, p75 interacts with a protein called p45, which can block this dimerization. Although a stop codon prevents expression of p45 protein in humans, there are implications for the development of a similar p75 inhibitor for therapeutic uses. Read more in the synopsis.

Category: Biology, Cell signalling, Disease, Genomics, Microbiology, Neuroscience, PLOS Biology, Regeneration, Research | Leave a comment

Introducing a New Look for the Journal Homepages

Today sees the launch of our re-vamped homepages for PLOS Biology, PLOS Genetics and PLOS Computational Biology.

 

Biology mock upThey’ve been designed to give easy access to all recently published work, and to better incorporate some of the beautiful images that accompany PLOS articles.

Take a look and see what you think:

www.plosbiology.org

www.plosgenetics.org

www.ploscompbiol.org

 

Category: Biology, Computational biology, Genetics, PLOS Biology, PLOS Computational Biology, PLOS Genetics, Publishing | Leave a comment

This week in PLOS Biology

In PLOS Biology this week, you can read about how ‘killer sperm‘ might prevent inter-species breeding, a new observation in the process of making stem cells, and an insight into parasitic tolerance in a long-studied population of sheep.

 

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Image credit: pbio.1001916

One characteristic often used to define a species is the inability to breed outside of it. Usually the consequences of doing so only extend to producing no offspring – or unsuccessful offspring (e.g. donkey + horse = mule). However new research by Janice Ting, Asher Cutter, Eric Haag and colleagues has unearthed altogether more sinister consequences. When males and females of different Caenorhabditid nematode worm species were mated, the lifespans of female worms were dramatically reduced and some were left sterile. Invading sperm was seen to destroy the ovaries and break through to other body tissues. They conclude that this ‘killer sperm’ could be a powerful evolutionary way to maintain a species barrier. For more background to this story, see the accompanying primer.

 

Somatic-cell nuclear transfer is a technique used to create an embryo from a body cell and an egg cell. It has become a focus of stem cell research for therapeutic uses. New research by Richard Halley-Stott, John Gurdon and colleagues makes an intriguing and potentially extremely useful observation about cell re-programming following these nuclei transplant experiments. When nuclei were transplanted from mouse muscle cells to amphibian eggs, nuclei taken during the mitotic phase of the cell cycle showed a much higher chance of reprogramming to form pluripotent cells than those taken in other phases of the cell cycle. The exact reasons behind this were not clear, but this research has important implications if selection for mitotic cells can improve the chances of producing stem cells.

 

CaptainOates

Image credit: Flickr user CaptainOates

Animals can adopt two strategies in response to parasitic infection: resistance or tolerance. In a new study using 25 years’ worth of data on wild sheep, Adam Hayward, Andrea Graham and colleagues look at individual variation in tolerance. They found that there was variation in how quickly individuals lost weight as parasite infections increased. Those that lost weight more slowly showed a higher lifetime breeding success. This suggests that natural selection can act upon tolerance in nature. This could have implications for human health and livestock management.

Category: Biology, Disease, Ecology, Epigenetics, Evolution, Immunology, Infectious disease, PLOS Biology, Research, Stem cells | Leave a comment

Making Biomolecular Simulations Accessible in the Post-Nobel Prize Era

PLOS Computational Biology Editor-in-Chief Ruth Nussinov and Guest Editor Qiang Cui introduce a freely available interactive step-by-step guide for performing common molecular simulation tasks integrated into the CHARMM INterface and Graphics web user interface. The three papers are part of our Education collection and can be found here: CHARMMing ICHARMMing IICHARMMing III.

In 2013, three pioneers of computational biophysics and structural biology, Martin Karplus, Arieh Warshel, and Michael Levitt, were awarded the Nobel Prize in Chemistry. Although the citation focused on their innovative efforts on integrating quantum mechanical and classical mechanical models to study reactive processes in proteins, the award has also been seen by many researchers in the biomolecular simulation field as recognizing the tremendous value of computations for the investigation of biomolecules in general. From the days when proteins were modeled at the picosecond timescale using a united atom representation [1], or even as coarse-grained beads [2], in vacuum, to modern simulations that approach the millisecond timescale for a fully solvated protein [3], the biomolecular simulation field has, indeed, come a long way. Much of the progress has been due to the efforts of the three laureates, their contemporaries, and many others (e.g., their students) who were inspired by their dream of understanding life by studying “the jiggling and wiggling of atoms” [4]. One could only admire the tremendous courage, imagination, and vision that drove these three scientists to start pursuing their dream in an era when theoretical and computational chemistry largely focused on understanding the interactions and reactivity of small molecules.

charmmingimage

Image credit: Pickard et al.

Just as the Nobel Prize in 1998 to John Pople and Walter Kohn highlighted both the impact and emerging challenges of quantum chemistry, the 2013 Chemistry Prize should also further inspire us to ponder about the future of computational biology. Clearly, developing methodologies that further enhance the quantitative accuracy and/or complexity of computational models are important and being actively pursued by many researchers. On the quantitative aspect, several community-wide blind tests on observables such as solvation free energies, binding affinities, and pKa values are being held. Provided that the results are disseminated in a constructive manner, these blind tests are highly valuable for helping the community converge towards the most robust and efficient computational algorithms and protocols. On the other hand, it is valuable to bear in mind that in many (certainly not necessarily all) investigations, quantitative computations represent a means to validate the model rather than the ultimate goal, which ought to focus on revealing the physical and chemical principles that govern the biological problem at hand. In other words, understanding qualitative trends is equally important. Therefore, building models with different levels of complexity and identifying robust features relevant to the biological problem remains an important research strategy. After all, in many mechanistic studies, whether at the molecular or cellular scale, the ultimate goal is to establish a conceptual framework to guide the development of novel mechanistic hypotheses and to stimulate new experiments to evaluate them.

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Image credit: Miller et al.

Another important issue worth emphasizing in this “Post-Nobel Prize era” concerns making high-quality biomolecular simulation protocols available to the bioscience community, especially to young researchers who have just entered the field and perhaps even researchers who are primarily experimentalists. Such efforts will be essential to further enhancing the impact of biomolecular simulations while maintaining a high level of integrity in the result. In this issue of PLOS Computational Biology, Woodcock and coworkers have made a major step in this direction by describing a set of web-based tutorials and tools for the simulation package Chemistry at HARvard Molecular Mechanics (CHARMM) [5–7]; the tools are fittingly and playfully referred to as “CHARMMing.” The web-based tools make it straightforward to set up complex biomolecular simulations, including reduction potential computation for proteins and molecular dynamics simulations using a coarse-grained model. For even an expert in biomolecular simulation, it is often cumbersome to set up a new simulation that requires the generation of force field parameters for cofactors; CHARMMing is helpful in this context by providing an easy access to several automated small molecule force field generation services (e.g., the ParamChem web-server, the MATCH toolkit).

Importantly, CHARMMing goes beyond simply facilitating the set-up of biomolecular simulations by including carefully designed lessons on topics that range from basic simulation tutorials to advanced protocols such as quantum mechanical (QM)/molecular mechanical (MM) calculations and enhanced sampling techniques. The graphic interface allows the “students,” who take those lessons, to understand and modify CHARMM input scripts as well as visualize simulation results. Therefore, CHARMMing is valuable not only as a research tool, but also an educational module that can easily be incorporated into curriculum at both the undergraduate and early graduate level. As a result, CHARMMing is complementary to another valuable web-based research tool, CHARMM-GUI [8], which features a number of sophisticated functionalities, such as setting up membrane simulations [9] and absolute ligand binding affinity calculations [10]. We hope that the set of CHARMMing papers will help stimulate additional efforts in bringing advanced simulations, good computational practices, and thorough analysis of simulation results to the broader biological research community. Although pushing the limit of computational research via method development is always essential, an equally important goal is, to paraphrase what Martin Karplus once stated [11], that experimental (structural) biologists, who know their systems better than anyone else, will make increasing use of molecular dynamics simulations for obtaining a deeper understanding of particular biological systems.

 

References

1. McCammon JA, Gelin BR, Karplus M (1977) Dynamics of folded proteins. Nature 267: 585–590.

2.  Levitt M, Warshel A (1975) Computer simulation of protein folding. Nature 253: 694–698.

3.  Shaw DE, Maragakis P, Lindorff-Larsen K, Piana S, Dror RO, et al. (2010) Atomic-level characterization of the structural dynamics of proteins. Science 330: 341–346.

4.  Feynman RP, Leighton RB, Sands M (1963) The Feynman Lectures in Physics. Reading: Addison-Wesley.

5.  Miller BT, Singh RP, Schalk V, Pevzner Y, Sun JJ, et al. (2014) Web based computational chemistry education with CHARMMing I: Lessons and Tutorial. PLoS Comput Biol 10: e1003719.

6.  Pickard FC IV, Miller BT, Schalk V, Lerner MG, Woodcock HL III, et al. (2014) Web-Based Computational Chemistry Education with CHARMMing II: Coarse-Grained Protein Folding. PLoS Comput Biol 10(7): e1003738. doi:10.1371/journal.pcbi.1003738

7.  Perrin BS Jr, Miller BT, Schalk V, Woodcock HL III, Brooks BR, Ichiye T (2014) Web-based computational chemistry lessons in CHARMMing III: Reduction potentials of electron transfer proteins. PLoS Comput Biol 10: e1003739.

8.  Jo S, Kim T, Iyer VG, Im W (2008) CHARMM-GUI: A web-based graphical user interface for CHARMM. J Comp Chem 29: 1859–1865.

9.  Jo S, Lim JB, Klauda JB, Im W (2009) CHARMM-GUI Membrane Builder for Mixed Bilayers and Its Application to Yeast Membranes. Biophys J 97: 50–58.

10. Jo S, Jiang W, Lee HS, Roux B, Im W (2013) CHARMM-GUI Ligand Binder for Absolute Binding Free Energy Calculations and Its Application. J Chem Info Model 53: 267– 277.

11. Karplus M, Kuriyan J (2005) Molecular dynamics and protein function. Proc Natl Acad Sci U S A 102: 6679–6685.

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Inaugural Centromere Biology Gordon Conference: Beth Sullivan

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, with posts written by the organizers or PLOS Genetics editors who are involved.

The next of these conferences is the Centromere Biology Gordon Conference, which takes place in Waltham, Massachusetts between the 27th of July and the 1st of August. Beth Sullivan, PLOS Genetics editor, says a few words about the conference and why she finds it exciting.

I’m Beth Sullivan, an Associate Editor for PLOS Genetics, and an Associate Professor of Molecular Genetics and Microbiology at Duke University in Durham, North Carolina, USA.

My lab’s research focuses on the centromere, a region of the chromosome that is required to faithfully pass on genetic information during each cell division. Research over the past three decades has indicated that in most organisms, both DNA sequence and sequence-independent factors define a centromere. Recent efforts have focused on the biology of a specific centromere protein called CENP-A. Many in the field are studying the structure of CENP-A protein complexes and how CENP-A is incorporated and maintained at centromeres. However, there is much more to centromeres than just CENP-A.

Conference Chair Rachel O’Neill (University of Connecticut, Storrs) and I are organizing the inaugural Centromere Biology Gordon Research Conference (GRC) to be held at Bentley University in Waltham, MA on July 27 – August 1, 2014.

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The Adamian Building at Bentley University, where the Centromere Biology Gordon Research Conference will be taking place. Image credit: Public Domain

For the past 25 years, the centromere community has grown steadily, encompassing many areas of centromere biology including genomics, epigenetics, chromosome engineering, and comparative genetics. Despite this increase in depth, there have been few meetings dedicated exclusively to topics in centromere structure and function.

Rachel O’Neill and I have been colleagues, friends, and collaborators for several years now. In early May 2012, we attended an editorial board meeting at Woods Hole, and amongst our conversations about running, shoes, and science, we found ourselves lamenting that the centromere field lacked a meeting in the U.S. that included a spectrum of speakers that represented the diverse areas of centromere research. We touched base with several colleagues in the centromere field, primarily to gauge if there was interest in a U.S.-based meeting. The answer was a resounding yes! Two weeks later, we submitted an application for a new GRC, and thanks to the support of several heavy-hitters in the field, we successfully joined the prestigious GRC portfolio.

Our goal for this meeting is to bring together U.S. centromere researchers, as well as those from around the world to present unpublished research on mechanisms of centromere biology, and to identify new and collaborative areas of study. Attendees and speakers are coming from as far away as India, Japan, Hong Kong, and Australia. Because so many other conferences are dominated by “the big names” in the field, Rachel and I wanted the Centromere Gordon conference to represent the diversity in the centromere field, both in topics and investigator status. We hope this conference will especially provide a forum to highlight research from trainee (graduate students and postdocs), junior investigators, and under-represented groups.

The conference program includes 9 sessions focused on topics that include the emerging area of centromere genomics, centromere organization and dynamics, CENP-A nucleosome dynamics and structure, coordination of centromeric domains, centromere-kinetochore interactions, synthetic/de novo/ectopic centromeres, centromeric RNAs and transcription, centromere evolution, and variant centromeres. The meeting begins and ends with keynote talks by two prominent leaders in the field, Steven Henikoff (HHMI, Fred Hutchinson Cancer Research Center) and William Earnshaw (Wellcome Trust Center for Cell Biology, University of Edinburgh). These two well-respected scientists epitomize different ends of the centromere biology spectrum, and their talks will serve to emphasize the research diversity within the field.

dicentric for PLOS

This image is of an induced/engineered dicentric human chromosome (center of image) created in the Sullivan lab at Duke University. It is immunostained for centromere protein CENP-A (green) and centromere protein CENP-B (red); chromosomes are counterstained with DAPI (blue). Several of the sessions at the meeting will focus on CENP-A dynamics, CENP-B’s role in centromere assembly, and the biology of ectopic (induced) centromeres and dicentric chromosomes. Image credit: Kaitlin Stimpson Woodlief

 

Defining genomic and epigenetic aspects of centromere function remains a primary goal of my lab’s research. As a graduate student at Case Western Reserve University, I studied Robertsonian translocations, and I still maintain a deep interest in dicentric chromosomes – i.e. those with two centromeres. In the late 1930s, Barbara McClintock first described the unstable behavior of dicentric chromosomes in maize. However, dicentric human chromosomes, which occur naturally at a frequency of one in 1000 livebirths, are quite stable, and are even transmitted through meiosis (i.e. parent to child). This is because they undergo centromere inactivation or suppression. How and when centromere inactivation occurs after dicentric formation is unclear, and is a question I hope to understand before my time in science is over. The fact that other scientists who also want to discuss and understand this biological problem will be gathered in a few weeks at the Centromere Biology GRC is something I eagerly anticipate.

Rachel and I are extremely appreciative that PLOS Genetics, a premier journal publishing excellent and cutting-edge science, is a sponsor of this new research conference. We hope that attendees of the Centromere Biology GRC will leave the meeting with fresh questions about centromeres, innovative ideas to tackle those questions, and beneficial new collaborations. At the very least, we hope everyone will return to the lab with a new or rejuvenated enthusiasm for centromere biology.

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This week in PLOS Biology

In PLOS Biology this week you can read about the development of a vital vessel in the eye, the structure of a protein involved in Vitamin K synthesis and how protein synthesis is maintained at both high accuracy and high speed.

 

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Image credit: pbio.1001913

Schlemm’s canal is a vital draining vessel which can be found in the eye, between the cornea and the lens. It collects aqueous humour and delivers it into the bloodstream:  it is therefore vital for preventing the build-up of pressure associated with ocular hypertension and glaucoma. Despite its importance, little is known about its development. New research by Krishnakumar Kizhatil, Simon John and colleagues characterised Schlemm’s canal development, and in doing so discovered a novel process of vascular development. The cells of the canal express proteins characteristic of both blood and lymphatic vessels. Understanding these processes may lead to better understanding of the workings of the canal and how it can be manipulated to control glaucoma. Read more in the accompanying synopsis.

 

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Image credit: pbio.1001911

Hua Huang, Ming Zhou and colleagues have used x-ray crystallography to determine the structure of a member of the UbiA family of integral membrane proteins. The protein structures were for an archaeal homologue of UBIAD1 – an important enzyme that attaches prenyl groups during the synthesis of Vitamin K and Coenzyme Q in humans. Determining structure allows function to be predicted – in particular how the enzymatic mechanism works.

 

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Image credit: pbio.1001910

When cells are growing at a rapid rate, protein synthesis via ribosomal translation needs to be both rapid and accurate to sustain growth. New research by Jian-Rong Yang, Xiaoshu Chen and Jianzhi Zhang analysed datasets on the budding yeast Saccharomyces cerevisae. They propose that secondary structure in mRNAs modulates the speed of protein synthesis, therefore improving accuracy at functionally important sites while ensuring high speed elsewhere. They argue that this demonstrates the power of natural selection in mitigating efficiency-accuracy conflicts, which are prevalent in biology.

Category: Bioinformatics, Biology, Computational biology, Developmental biology, Disease, Evolution, Molecular biology, PLOS Biology | Leave a comment

FASEB Summer Research Conference on Dynamic DNA Structures in Biology: Sergei Mirkin

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, with posts written by the organizers or PLOS Genetics editors who are involved.

The next of these conferences is the FASEB Summer Research ConferenceDynamic DNA Structures in Biology, which takes place in Itasca, Illinois between the 20th and 25th of July. We asked Sergei Mirkin, an organizer of the conference and Chair of Biology at Tufts University, about the meeting, and the aspects of dynamic DNA structures that he finds exciting.

Where are you from? What do you research? What is the conference about?

I am Sergei Mirkin, a Chair of Biology at Tufts University and organizer of the FASEB Summer Research Conference “Dynamic DNA Structures in Biology”. This topic is very close to my heart, since I have devoted most of my research career to it. During my Ph.D. training at the Institute of Molecular Genetics, Russian Academy of Sciences, I studied the role of DNA supercoiling in DNA replication and transcription in E. coli. At about this time, the paradigm that DNA is nothing more than a regular, right-handed double helix began to change following the discovery of left-handed Z-DNA by Andrew Wang and Alex Rich, and DNA cruciforms by David Lilley and Bob Wells. These developments ignited my interest in structural transitions in DNA.

During my postdoctoral years we, together with Victor Lyamichev and Maxim Frank-Kamenetskii, found a totally unexpected DNA structure, called H-DNA, the main element of which was intramolecular triple-helix. This was the first demonstration for the presence of multi-stranded structure in natural DNA! This striking finding was soon followed by the discovery of Dipankar Sen (a speaker at this conference) and Walter Gilbert that functionally important DNA motifs can form four-stranded, G-quartet DNA. Subsequently, more alternative DNA structures came to stage, including DNA Unwinding Elements (DUE) by David Kowalski, i-motifs by Maurice Gueron, mismatched hairpins by Cynthia McMurray (a keynote speaker at the conference), slipped-strand DNA by Christopher Pearson (a speaker at the conference) and Richard Sinden and others.

Dynamic DNA Structures. Image Credit: Sergei Mirkin

Dynamic DNA Structures. Image Credit: Sergei Mirkin

While these were exciting developments, the biological role for any of these structures remained completely unclear. A particularly challenging problem was the detection of these structures inside living cells. It took our community another decade or so to realize that, since formation of these structures requires extensive DNA strand separation, they are only transiently formed during the genetic transactions involving DNA unwinding, such as DNA replication and transcription, explaining the difficulties with their detection in vivo.  The term “dynamic DNA structures” was then coined to account for their transient nature.

More recently, we began to understand the biological consequences resulting from the formation of dynamic DNA structures in the course of major genetic processes. One of the most striking examples was the discovery that expansions of structure-prone DNA repeats leads to more than thirty hereditary neurological and developmental diseases in humans. Dynamic DNA structures are actively involved in normal genome functioning including transcriptional activation, regulation of antigenic switching and DNA recombination essential to the immune response.  At the same time, they were linked to chromosomal fragility and chromosomal translocations observed in human cancers and genetic diseases. In an unexpected twist, DNA structures appeared to be quite useful for nanotechnology, where their unusual physical properties find many applications.  Consequently, the interest in dynamic DNA structures is high and continues to grow with new discoveries of their biological roles, as well as their uses.  All these topics will be discussed at the proposed FASEB Dynamic DNA Structures meeting.

How did you come together to put on this conference? What are you hoping to accomplish over the few days?

The idea to organize a FASEB conference devoted to these structures first came to Alison Ratray and Susanna Lewis back in 2008: the prime focus of the first conference were DNA cruciforms and hairpins. The second conference with a broader focus on alternative DNA structures was co-organized by Alison, Susan and Nancy Maizels in 2010. In 2012, Nancy Maizels and myself co-organized the third one, which held its current name: Dynamic DNA Structures in Biology.  This year, I co-organize it with Sue Jinks-Robertson and Alain Nicolas. I really admire this forum, as it provides us with a flow of ideas and discussions on the role of dynamic DNA structures in various genetic processes. By everyone’s account these conferences have energized our field and have given us plenty of new ideas and experimental directions! I am therefore looking forward to spending a week at this exciting conference.

If you could collaborate with one scientist from any period of time, who would it be?

Francis Crick back in the 1950s/1960s. I cannot think of a scientist, who has made bigger contribution to molecular biology! There are two problems with this wish, however: (i) I had only just been born at that time, and (ii) even if I were grown up, Francis would probably kick me out for not being smart enough to catch up with him… In any event, I would love to give it a try!

Category: Biology, Blog, Community, Conference, Genetics, Genomics, PLOS Genetics, Uncategorized | Tagged , , , , | 1 Comment

You Just Read my Mind…

STOP PRESS!Scientists decode words from brain signals, fueling hopes for mind reading!” “Mind-reading device could become reality!” “Scientists make telepathy breakthrough!” “Secrets of the inner voice unlocked!” – just some of the sensational headlines that greeted a PLOS Biology research article a couple of years ago. OK, so I might’ve put the exclamation marks in myself, but the science behind the claims was indeed pretty extraordinary.

Spectrograms of the original stimulus (top) and reconstructed speech (bottom). doi:10.1371/journal.pbio.1001251.g002

Spectrograms of the original stimulus (top) and reconstructed speech (bottom). doi:10.1371/journal.pbio.1001251.g002

I’ll talk more about the study itself in a moment, but how do you know when you’ve published a great paper? Traditionally it would be a matter of counting journal citations, but that captures only one strand of the complex set of influences that a paper can have. Now we can separate out these strands and follow them, each with its own characteristic. The quick spike of Twitter, the steady spread on Facebook, the rash of saves in Mendeley, of citations in F1000Prime, the complex dynamics of html page views, PDF downloads, secondary coverage in scientific and popular media and in the blogosphere, and – yes – the slow-burn of journal citations. Each has its own time course, its own demographic (age, field, background) and its own texture. And each speaks to a subtly different aspect of the work’s appeal.

There are methodological papers that emerge unnoticed and become citation classics, and there are papers on intriguing animal behaviour that are splashed across the tabloids but have single-figure citations. Two very valid forms of impact, but back in 2012 we published a truly fascinating paper, and two years of metrics show that it managed to hit both buttons very firmly.

Much of neuroscience arguably involves subjecting an animal to a stimulus and then trying to find out how the brain responds. This paper describes a spookily successful attempt to achieve the reverse – looking at the brain’s activity and trying to reconstruct the stimulus that must have caused it. By placing electrodes directly in contact with the auditory cortex, they were able to “mind-read” the words that the person had heard. Listen to this incredible recording of spoken words paired with their “mind-reading” reconstruction:

 

Red circles show the position of electrode arrays on the surface of the superior and middle temporal gyrus. doi:10.1371/journal.pbio.1001251.g001

Red circles show the position of electrode arrays on the surface of the superior and middle temporal gyrus. doi:10.1371/journal.pbio.1001251.g001

Normally the human cerebral cortex lies nicely protected by the cranium, but in this study the authors were able to exploit an extraordinary opportunity. Medics removing tumours or epileptic tissue from highly sensitive parts of the brains of fifteen patients were eager to keep their patients awake so that they could check that they didn’t affect anything crucial. This gave the authors a 10-12 minute window of time when the cortex of an alert patient was exposed to the atmosphere.

During this period an array of electrodes was placed on the surface of the auditory cortex and recordings were made while single words were spoken to the patient. The signals received were used to construct a computational model of the relationship between the stimulus (“Waldo”) and the representation in the brain. This relationship could then be flipped to reconstruct a passable (and recognisable) reproduction of the original spoken word (“Woodor”).

Read the full paper for the details of research, listen to the astonishing audio file of the reconstructed speech, and for a lively discussion with authors Brian Pasley and Bob Knight, I strongly recommend that you listen to Ruchir Shah‘s excellent PLOS Biology podcast (some more remarkable recordings of the speech stimuli and their paired reconstructions appear at 11:15-12:10). In their discussion, they reveal that a long-term translational aim is to use the brain activity elicited by people’s imagined words to drive a prosthetic speech device for those who are unable to speak.

To date the paper has received nearly 85,000 page views, including over 9,000 PDF downloads, and has been cited 66 times already (see more metrics here). It’s the 48th most saved PLOS article in Mendeley of all time, is cited in two Wikipedia entries (“Thought Identification” and “2012 in Science“), and has respectable Facebook activity (21 likes, 467 shares, 33 posts). Twitter looks a bit thin on the ground because we only started collecting stats 5 months after the paper was published, so missing the main spike. But as well as the healthy academic attention, the article attracted massive press coverage that taps liberally into the memes of mind-reading and telepathy, and has inspired bloggers from Wales to Brazil. Now that’s a great paper.

Category: Biology, Computational biology, Debate, Neuroscience, PLOS Biology, Publishing, Research | 2 Comments

This week in PLOS Biology

In PLOS Biology this week, you can read about new research on the making of the vertebrate neural tube and a chemical modification essential for the functioning of inhibitory synapses in the brain.

 

pbio.1001908

Image credit: pbio.1001908

Efficient signal transmission at synapses is essential for higher brain functions. Inhibitory signalling in the brain mainly takes place at GABAergic synapses. Gephyrin is an intracellular component of the postsynaptic protein network in these inhibitory synapses (i.e. on the “receiving” side of the synapse), and importantly, is responsible for clustering GABA receptors at the synaptic membrane. Borislav Dejanovic, Guenter Schwarz and colleagues demonstrate that in order to perform its function, gephyrin needs to be modified by palmitoylation – the reversible posttranslational attachment of the fatty acid palmitate (commonly used to make soaps).

 

pbio.1001907

Image credit: pbio.1001907

A relatively small number of signals are responsible for the variety and pattern of cell types generated in developing vertebrate embryos. The diversity in cell types depends, at least in part, on changes in the way cells respond to each signal. In new research Noriaki Sasai, Eva Kutejova and James Briscoe looked at neural cord development in chick and mouse embryos, and found that in order to specify two important cell types (Floor Plate and Neural Crest) FGF signalling needs to integrate with two perpendicular signalling pathways (Shh and BMP).

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