This week in PLOS Biology

In PLOS Biology this week you can read about a survival strategy employed by Salmonella bugs, transcript capping in the cytoplasm and differences in the architecture of the visual cortex between rodents and higher mammals.

 

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Image credit: image.pcbi.v06.i08.g001

The mammalian visual cortex contains 50 to 100 thousand neurons per cubic millimetre, most of which are excitatory (85%) and the minority, inhibitory (15%). Unlike neurons in the retina, neurons in the visual cortex are preferentially activated by lines or edges of a particular orientation. In the visual cortex of higher mammals like cats and monkeys, neurons that share an orientation preference are clustered in functional columns. However, in rodents like mice, orientation preferences are randomly distributed. In a new study, Rita Bopp, Morgane Roth and colleagues asked whether the differences between columnar and non-columnar cortex are correlated with differences in the connectivity patterns between excitatory and inhibitory neurons in mice. Their results show that the ratio of excitatory-inhibitory neurons in the mouse visual cortex is similar to that of cat or monkey visual cortex, but in the mouse local pyramidal neurons target proportionately many more inhibitory neurons compared to other studies in higher mammals. This suggests that inhibition may stand in for columns as the organising principle.

 

Bacterial populations grow rapidly and asexually, generating millions of genetically identical progeny. However despite genetic and environmental uniformity, we now know that differences can occur, through stochastic molecular processes. But what are the advantages of this in a group of clonal organisms? Markus Arnoldini, Martin Ackermann and colleagues studied the human pathogen Salmonella typhimurium, which is known to vary in levels of virulence factors called ttss-1. Those bugs which express high levels of the factor grow slower, but the authors showed that they were also better able to survive antibiotic treatments. So it seems that this is a ‘bet-hedging’ strategy that pays off when disaster strikes. This has implications for antibiotic use, as selection for tolerance of the drug might also inadvertently select for high virulence. Read more in the accompanying synopsis.

 

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Image credit: pbio.1001933

Messenger RNA ‘capping’ was previously thought to happen only in the nucleus, with subsequent degradation in the cytoplasm. However there has been recent evidence of capping taking place in the cytoplasm. In this week’s issue of PLOS Biology work by Chandrama Mukherjee, Baskar Bakthavachalu and Daniel Schoenberg build on this discovery. They have identified a domain of the cytoplasmic Capping Enzyme, which is required for its function in cytoplasmic capping. This allows it to bind to the adapter protein Nck1 – Nck1 is better known as a player in kinase-mediated signalling pathways, but here they show that it also helps provide a scaffold for assembly of the cytoplasmic capping complex.

 

 

Category: Biology, Cell biology, Evolution, Infectious disease, Microbiology, Molecular biology, Neuroscience, PLOS Biology, Research | Leave a comment

What’s the Buzz on Bee Pathogens?

US National Honey Bee Day is August 16th. Read below for a selection of papers from PLOS Pathogens on honey bee decline in the world of pathogenesis. 

Honey bees at a hive entrance. Image credit: Warden, Wikimedia Commons

Honey bees at a hive entrance.
Image credit: Warden, Wikimedia Commons

Given the current issues affecting global health— the Ebola outbreak in West Africa, the battle to eradicate polio in Pakistan, and the rise of type 2 diabetes in the United States— honey bee health seems like it would be last on our list of worries. However, August 16, 2014 marks the 5th US National Honey Bee Day, an organized day to raise honey bee awareness. Honey bee health and the awareness day commemorating it seem mainly geared towards the agricultural, farming, and small-scale bee-keeping communities; however, there is more interest in honey bee health from the scientific community than you may think.

The decline of honey bees, known in the scientific community as colony collapse disorder (CCD), is a major agricultural concern and the Agricultural Research Service (ARS)— the USDA’s internal research agency— is leading several efforts to gain more information on the possible causes of CCD. The rate at which honey bee colonies are declining is alarming. According to the 2013-2014 annual survey conducted by the Bee Informed Partnership and the U.S. Department of Agriculture (USDA), total losses of managed honey bee colonies from all causes were 23.2 percent nationwide for the 2013-2014 winter.  The honey bee industry is vital to large agriculture which feeds most of the world; however National Honey Bee Day is aimed at increasing involvement from concerned citizens, most of whom are backyard gardeners and nature-loving beekeepers.
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This Week in PLOS Biology

In PLOS Biology this week you can read about a regulatory pathway in meiosis, genetic variability of avian influenza and ancient cell membranes.

 

Meiosis is a type of cell division which is essential for halving the number of chromosomes to make gametes needed for sexual reproduction in animals, plants and fungi. A further feature of meiosis, and one of the main driving forces behind the success of sex, is that it affords the organism a chance to shuffle its genome, using well distributed recombination events (“crossovers“) to make a new meld of its parents’ genotypes. Although crossovers benefit from being randomly placed, their number and approximate position needs to be tightly regulated. In a new research article by Marina Jahns, Mathilde Grelon and colleagues, they investigate how this is done. They identified a novel regulatory pathway controlling crossover localisation in Arabidopsis plants, which may also be conserved in mammals. This pathway involves post-translational modification via neddylation (covalent attachment of the ubiquitin-related protein Nedd8).

 

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Image credit: journal.pbio.1001931

Despite the public health significance of Avian influenza viruses (pivotal to the origination of human pandemic strains) much is not understood about their ecology and evolution in wild birds. The host pool in birds supports a very large range of strains, but once in humans the genetic diversity is much reduced. Benjamin Roche, Pejman Rohani and colleagues present comparative analyses of human and avian viruses and use computational models to try to explain these differences. They conclude that the combination of the short lifespan of wild birds, and greater durability of viruses in aquatic environments, is key to maintaining the high levels of flu virus diversity observed in wild birds.

 

 

 

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Image credit: journal.pbio.1001926

The archaea and the bacteria – the two deepest branches of the tree of life. They share many features in common, but their cell membranes are profoundly different. It seems therefore that the membranes must have evolved after the two diverged from their last universal common ancestor (“LUCA”). But if that ancestor did not have a membrane, how could it harvest energy, and why did the archaeal and bacterial progeny produce such different membrane structures? Victor Sojo, Andrew Pomiankowski, and Nick Lane developed a mathematical model of primordial membrane bioenergetics, showing that a leaky membrane of simple lipids could be a precursor of both types of modern membrane. Read more in the accompanying synopsis.

Category: Biology, Cell biology, Computational biology, Disease, Ecology, Evolution, Genetics, Infectious disease, Microbiology, Molecular biology, Plant biology, PLOS Biology, Research | Leave a comment

Gordon Research Conference on Mammalian Reproduction: Marisa Bartolomei

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 last of these conferences is the Gordon Research Conference on Mammalian Reproduction, which takes place at Colby Sawyer College from the 10th to the 15th of August. Marisa BartolomeiPLOS Genetics editor who will be chairing the discussion on Epigenetic Programming and Reproduction, describes the topics that will be discussed at the conference, and their relevance to everyday life.

A new Gordon Research Conference (GRC) on Mammalian Reproduction is being launched this week. This conference will continue the legacy of two previous GRCs dealing with aspects of mammalian reproduction – one on Mammalian Gametogenesis & Embryogenesis and one on Reproductive Tract Biology.  Both of those GRCs ran successfully for more than 30 years but were stopped around three years ago.  This new GRC on Mammalian Reproduction seeks to combine the best of the legacies of those two meetings to create a new conference focused on cutting-edge research of greatest relevance to the field of reproductive biology as it applies to mammals.

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Image credit: Public domain

 

The theme of this inaugural gathering in what we hope will become another long-standing and successful GRC on reproduction is “Translating Basic Science into Clinical Applications.”  To this end, sessions are focused on topics in which novel basic discoveries have lead and/or are leading to novel and effective clinical applications.  The opening session will focus on “Fate Determination and Development of Reproductive Tissues,” which will feature recent discoveries into developmental origins of germ cells and somatic cells in reproductive tissues.  Such insight can be used to help understand how defects in these developmental mechanisms may lead to infertility or to diseases of reproductive tissues.  In addition, these developmental mechanisms can be replicated to direct differentiation of stem cells to restore these functions.

The second session will focus on “Epigenetic Programming and Reproduction.” The reproductive system – especially the germ line – is a site of extensive epigenetic programming/reprogramming during each generation.  These mechanisms are responsible for proper development of each generation, and defects in these mechanisms can lead to transgenerational epigenetic inheritance resulting in heritable transmission of disease via a non-genetic paradigm.  A related topic will be explored in the third session – “Stem Cells and Reproduction.”  Once again, a basic understanding of the manner in which normal endogenous stem cells function in the reproductive system will provide insight into how exogenous stem cells can be used to treat reproductive defects including infertility or disease.  In yet another related session – “Environmental Effects on Reproductive Functions” – the manner in which various environmental agents can disrupt normal reproductive functions will be explored.  This has become a particularly active area of research in recent years and this conference will bring together experts from the reproductive biology and environmental health fields to further address key questions in this area.

In the fifth session, the conference will transition its focus to questions of women’s health and infertility and contraception.  Thus, the fifth session will focus on “Pregnancy and Parturition” and will address key immunological and pathological mechanisms operating during this time.  The sixth session will then be focused on “Infertility and Contraception” and will include presentations describing new information regarding molecular mechanisms that impact fertility, as well as those describing novel approaches to contraception.

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Image credit: gabi menashe Flickr CC BY

The seventh session will focus on the male reproductive system and male fertility with an emphasis on mechanisms operating in the “Male Reproductive Tract.”  Then in the eighth session, the focus will turn to larger scale “Genomics/Systems Biology Approaches to Reproduction.”  This will include studies utilizing genomics, transcriptomics, and other high-throughput approaches to more comprehensively examine reproductive functions. Epigenetics section editor Wolf Reik will present a talk in this session describing the role of DNA modifications in signaling in epigenetic reprogramming.

The final session is entitled the “Founders’ Forum – Milestones in Reproductive Biology.”  This is a special session that recognizes senior investigators in the field who have made particularly significant and extensive contributions to the field.  This forum affords these individuals an opportunity to present their most recent work and to place that in a large historical context related to the particular sub-discipline under the reproduction umbrella in which they are most interested.

In addition to invited longer talks, the conference will feature a number of short talks by young investigators, from graduate students to assistant professors. There are also more than 100 posters that will be presented from Monday to Thursday afternoon. We are thrilled that over 150 people have registered to attend this inaugural Gordon Research Conference.

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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.

 

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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.

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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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