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This month on the Node – November 2012

Posted by , on 30 November 2012

Site upgrade
We now have a “featured topics” bar across the top of the page, which has the same function as these highlight posts: to let you know what happened on the Node recently.

This upgrade also came with author profile page. Do remember to fill out your profile bio, because people can now see this when they click your name on a post you wrote on the Node. Here’s how to do that.

Publishing discussion
A post from last month has started to generate an interesting discussion in the comments section about the future of scientific publishing. Have a look at the comments from scientists and publishers that were left on Jordan Raff’s BiO editorial, and add your own thoughts.

Multimedia conferences
audienceRachael went to a meeting at the Royal Society about long-range control of gene expression, and Eva attended SpotOn London (about science policy, outreach, and tools). You can read their reviews of the meetings on the Node, but you can also relive both meetings more directly: the Royal Society is making audio of the talks available online, and SpotOn has video of each conference session.

Also on the Node
BCSB science writing competition
Sox1 marks neural stem cells in the hippocampus
new job ads!

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Book review: An introduction to decoding genomes

Posted by , on 29 November 2012

This book review originally appeared in Development. Jennifer Mitchell reviews “Introduction to Genomics” (by Arthur M. Lesk).

Book info:
Introduction to Genomics By Arthur M. Lesk. Oxford University Press (2011) 424 pages ISBN 978-0-19-956435-4 £34.99 (paperback)

The past 20 years has seen a revolution in genomics. From the completion of the human genome in 2003, which took 13 years, we are well on our way to achieving the next benchmark goal of having 1000 human genomes sequenced (The 1000 Genomes Project). This endeavour will provide a deep catalogue of human genetic variation. In addition, and as part of The Genome 10K Project (which aims to sequence the genomes of 10,000 vertebrate species), 2012 saw the initial assembly of the medium ground finch (Geospiza fortis) genome, one of the iconic Galapagos finches described by Charles Darwin. The results of these genome sequencing projects are available through freely accessible public databases, thus accelerating discoveries in diverse fields of biology. With the advent of next-generation sequencing platforms, the time and cost of sequencing have dropped dramatically, making the ability to sequence the human genome in a day for less than $1000 no longer science fiction but rather an event that will happen in the immediate future. The effects of this genomics revolution are widespread, and no field of biology or medicine remains untouched by the changes in sequencing throughput. Furthermore, genomic studies are so commonly highlighted by the media that a working understanding of genomics is increasingly important in undergraduate biology education.

The second edition of Introduction to Genomics by Arthur M. Lesk is a comprehensive introduction to genomics that covers a diversity of topics, from genome sequencing to systems biology approaches used for understanding the metabolome, transcriptome and proteome. This new edition strives to highlight the progress made in genomics due to the increased application of high-throughput sequencing techniques. The text is accessible to undergraduate students; it does a thorough job of providing the basic principles before moving on to more in-depth concepts. The author presents an important discussion of the ethical issues surrounding genome sequencing, including the efforts taken to protect individuals who contribute samples to the large-scale human genome sequencing projects that are currently underway. These issues are presented in a well-balanced and unbiased manner. Importantly, the text is a pleasure to read; detailed colour illustrations are provided throughout, as well as helpful analogies that allow the reader to get to grips with difficult concepts. For example, biological networks are compared to the London Underground map, where the stations are the nodes and the edges the tracks that connect them.

This new edition highlights recent advances in sequencing techniques while still presenting the historical context for the discovery of genomes. Early in the text, the history of the discovery of DNA structure, the need to understand the ‘language of the genome’, and early progress in sequencing techniques are discussed in a narrative manner. Lesk writes, “the sequence of the bases was like a text everyone wanted to read, not only was the text in an unknown language, but there were not even any examples of the language, because the sequences were unknown”, thus framing the importance of early DNA sequencing efforts in ultimately decoding the human genome. This leads into the development of Sanger sequencing, a method developed by Frederick Sanger, and the sequencing of the 5386 bp ΦX174 bacteriophage genome, the first completed DNA genome sequence. Following on from this is the adaptation of Sanger sequencing to automated DNA sequencing using fluorescent tags and next-generation high-throughput sequencing techniques. As in the rest of the book, colour illustrations are used to great effect to explain the techniques and to provide examples of data output. These examples of data output are increasingly important, as so few students today will ever perform a Sanger sequencing reaction and see how the individual base-terminated chains resolved on the gel are composed into a sequence. So, although this technique has been replaced with higher throughput variations, the visual understanding of the sequencing process provided by inspecting a Sanger sequencing gel remains unmatched.

At the end of each chapter, selected additional reading is provided with problems that test the concepts discussed. The problems posed range from testing the basic understanding of the material to more thought-provoking questions that will allow students to test and deepen their understanding of the material. Of special note are the ‘weblem’ problems, which require the use of online genomics resources. These encourage students to develop a proficiency in the use of these resources, many of which are linked to the text through the publisher’s website. A ‘guided tour’ of genomics websites provides a list of websites with short descriptions and links to instructions or tutorials where available; however, this is merely a teaser that will hopefully push young scientists to explore more thoroughly the information that is available online to the scientific community.

Although the second edition is updated with expanded content, the information on data gathered from next-generation sequencing projects is rather limited. However, as the author points out, this is a moving target with advances made weekly, and it is therefore difficult to ensure that the material is up to date in a text of this type. Even with this in mind, I found that the section on deep sequencing of transcriptomes and functional genomics could have been expanded upon; there is a huge wealth of genome-wide functional genomics data for human, mouse, fly and worm genomes generated by the ENCODE and modENCODE projects, which are only briefly mentioned (Gerstein et al., 2010; modENCODE Consortium, 2010; ENCODE Project Consortium, 2011). These data are easily accessible through online browsers (UCSC Genome Browser, modENCODE GBrowse), massively accelerating the discovery of new genes, non-coding RNAs and regulatory elements such as enhancers and insulators. With the focus on students exploring genomics data on the web, these resources could have been better highlighted.

Given the widespread impact that sequenced genomes have on research, medicine and the general public, an introductory text such as this is an important resource. Introduction to Genomics is beautifully illustrated, supported by end of chapter and additional online resources, and written in an eloquent and readable style. Beyond focusing on genome sequencing and comparative genomics, a good deal of the text is concerned with transcripts, proteins and proteomics. However, there is minimal mention of transcriptional regulatory regions of the genome. I would have liked to see more emphasis given to transcription factor binding in the genome, epigenetic modifications and chromatin features, which are proving invaluable in identifying intergenic regulatory regions. Given the observation that disease-linked single-nucleotide polymorphisms are more often found in non-coding than in coding regions (Manolio, 2010), understanding how regulatory regions function is crucial in decoding the human genome and understanding predisposition to disease. Nonetheless, Introduction to Genomics is a comprehensive textbook that provides a solid introduction to the study of genomes and will be a great resource to undergraduate students with a background in molecular biology. The text also provides a useful resource for graduate students in other fields who want to make use of the growing number of online genomics resources.

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Coming Soon

Posted by , on 29 November 2012

We recently asked you what your favourite papers of 2012 were. From December 1 to 24, you’ll be able to see 24 of these papers behind the virtual doors of our advent calendar. Come back each day, click the calendar in the sidebar, and find out what your colleagues – from students to lab heads – have recommended.

New papers will go up each day at 8AM GMT.

We have contacted the publishers of the recommended papers that were behind a pay wall, and are happy to report that they’ve agreed to give you free access to the papers on at least the day they are featured. Many thanks to all publishers!

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Mammalian epigenetics in biology and medicine – NEW from Royal Society Publishing

Posted by , on 27 November 2012

Royal Society Publishing has just published Mammalian epigenetics in biology and medicine, compiled and edited by Fumitoshi Ishino,Yoichi Shinkai and Emma Whitelaw. See – http://bit.ly/RGO3Y0 for further details or you can go straight to the issue contents at http://rstb.royalsocietypublishing.org/content/368/1609.toc The issue (and ALL Royal Society content) is currently freely available to access online until 29th November 2012. The print issue is available at the special price of £35.00. You can order online via the above web page (enter special code TB 1609 when prompted) or, alternatively, you can contact debbie.vaughan@royalsociety.org

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The BSCB Science Writing Competition- time to start writing!

Posted by , on 27 November 2012

Have you got a great science story in you? This autumn, the BSCB is again running its Science Writing Competition! The judges are looking for interesting, enthusiastic articles covering topics of key relevance in biomedical science- this can mean a piece on research but also other topics relevant to cell biology, such as science policy or the impact of research on society. Most importantly, they must be original and entertaining for a non-specialist audience! The prize is £300, as well your article published in the BSCB newsletter and online- so a great chance to communicate your science and views to a wider audience!

To find out more details on this competition, as well as read last year’s winning entry, check the BSCB website: www.bscb.org

THE DEADLINE HAS NOW BEEN EXTENDED TO THE 15TH OF FEBRUARY

 

Some more information:

Eligibility

This competition is open to BSCB students and postdoctoral members only (but membership costs only £15 for students and £35 for postdocs, and includes reduced rates for BSCB meetings, access to travel grants, etc- so why not join the BSCB anyway!).

Topic

Articles should cover topics of key relevance in biomedical science. Articles need not be limited to research areas but you might like to try to communicate your own project in a clear, concise and entertaining way to a non-specialist audience. Other topics should be relevant to cell biology in its broadest context; examples could include the impact of stem cell technology, a feature on an important disease condition, or a wider science policy issue such as government funding of basic versus translational science.

Article characteristics

Articles should be limited to 1000 words but can include images where relevant (note that these will be reproduced in black and white only in the newsletter).

Deadline and submission

The deadline for submission is the 1st of February, 2013. Entries should be sent to Paul Andrews (pdandrews1@mac.com) as electronic files (preferably Word format with any illustrations or images sent separately as TIFF or JPG). (Deadline has now been extended to the 15th of February)

Please visit www.bscb.org for up-to-date information and more details.

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Categories: News

Featured posts and author pages

Posted by , on 26 November 2012

Notice something different on the Node today?

We now have a bar at the top to feature particular posts. It will be updated by Node admins, who select posts to appear here. (N.B. If you see text but not in neat little boxes, your browser still remembers the old design. Refresh page and/or clear cache and it should work.)

This change was inspired by feedback we gathered last year in our user survey. We discovered that the Node has a lot of readers who visit regularly but infrequently. That means that a lot of posts are no longer on the front page when they visit, and these infrequent readers may miss interesting things.

We started doing monthly highlights posts to summarize what was new on the Node each preceding month, but those get bumped down as well. The ideal solution was to have something in place in the site design, and now we finally have that. We hope you like it!

Another design change is the background – or rather, the lack thereof. We’ve moved from a dark background to a banner image only. The banner images still rotate, just like the old backgrounds.

Finally, there’s one change we told you about before. We now have author pages! If you click the author name on a post, you can see their profile, which includes a bio, a link to their personal or lab website (if they have one) and a list of all their posts on the Node.

Here’s Erin Campbell’s profile page, for example:

To set your bio and website, please follow the instructions here.

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Categories: News

Post-Doctoral Research Associate position at University College London

Posted by , on 23 November 2012

Closing Date: 15 March 2021

Post-Doctoral Research Associate position at University College London Cancer Institute

The group is based at the Cancer Institute at UCL and works on modelling inherited and acquired haematopoietic diseases using the zebrafish. The goal is to generate relevant models to study the genetics of these disorders and perform chemical screens to identify novel therapeutic targets for haematological cancers and pre-cancerous conditions.

Applicants must have or be in the process of submitting a PhD in a relevant biological science subject.

Experience of molecular cell biology (cloning, DNA/RNA extractions, qPCR, RT-PCR, W.blotting) is essential.

Experience of generating targeting constructs & working with zebrafish would be desirable.

For further information please contact Dr Beth Payne (e.payne@ucl.ac.uk)  http://www.ucl.ac.uk/cancer/rescancerbiol/zebrafish

For further details about the vacancy and how to apply on line please go to http://www.ucl.ac.uk/hr/jobs/ and search on Reference Number 1295744.

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Categories: Jobs

Postdoctoral Positions

Posted by , on 21 November 2012

Closing Date: 15 March 2021

POSTDOCTORAL POSITIONS are available to study different aspects of

mammalian organogenesis, with a particular focus on the cellular and

molecular mechanisms controlling the development of the visual system

and the lymphatic vasculature using available mouse models. Highly

motivated individuals who recently obtained a PhD or MD degree and have

a strong background in molecular, cancer and developmental biology are

encouraged to apply. Interested individuals should send their curriculum

vitae, a brief description of their research interests, and the names of three

references to:

 

Guillermo Oliver, PhD

Department of Genetics

St. Jude Children’s Research Hospital

332 N. Lauderdale, Memphis, TN 38105

E-mail: guillermo.oliver@stjude.org

http://www.stjude.org/oliver

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In Development this week (Vol. 139, Issue 24)

Posted by , on 21 November 2012

Here are the highlights from the current issue of Development:

 

Translating Apc1 loss into intestinal proliferation

Most colorectal cancers carry inactivating mutations in adenomatous polyposis coli (APC), a negative regulator of Wnt signalling. Moreover, in mice, Apc inactivation is sufficient to drive intestinal hyperplasia. Now, Julia Cordero, Owen Sansom and colleagues use the adult Drosophila midgut to identify the signalling pathways that mediate intestinal hyperplasia following Apc loss (see p. 4524). The researchers show that the Wnt target Myc is required for Drosophila intestinal stem cell (ISC) hyperproliferation following Apc1 loss. Egfr and Jak/Stat signalling are both activated in a Myc-dependent manner following Apc1 loss, they report, and are required to drive ISC hyperproliferation. Notably, Apc1 loss in ISCs results in non-cell-autonomous upregulation of the interleukin-like ligands Upd2/3 in enterocytes and subsequent activation of Jak/Stat signalling in ISCs. These and other findings indicate that non-cell-autonomous crosstalk between the Wnt/Myc, Egfr and Jak/Stat signalling pathways regulates intestinal hyperproliferation in the Drosophila midgut following Apc1 loss and suggest that these pathways may also be activated in human colorectal cancers

 

Maelstrom regulation of oocyte determination

The conserved protein Maelstrom has multiple functions during Drosophila oogenesis. It is a component of the perinuclear nuage, a germline structure in which the piRNAs that are required for transposon silencing are produced. In addition, Maelstrom localised within the nucleus promotes germline stem cell differentiation by repressing expression of the microRNA miR-7. Here (p. 4505), Toshie Kai and co-workers describe a third way in which Maelstrom regulates oogenesis. They show that Maelstrom is phosphorylated in Drosophila ovaries and identify its conserved serine 138 residue as the phosphorylation site. Maelstrom phosphorylation, they report, is required for oocyte determination but not for transposon silencing or for germline stem cell differentiation. They also show that phosphorylation of Maelstrom represses the pachytene checkpoint (one of the two meiotic checkpoints in Drosophila), in part through downregulation of the checkpoint protein Sir2, and identify Polo as a kinase that mediates Maelstrom phosphorylation. Thus, the researchers propose, Polo-mediated phosphorylation of Maelstrom regulates oocyte determination in Drosophila ovaries by inactivating the pachytene checkpoint.

 

Key role for LIN28 in nucleologenesis

A functional nucleolus (the organelle that makes ribosome subunits) is essential for embryonic development. Nucleologenesis, which involves transformation of an inactive nucleolar precursor body (NBP) into a mature nucleolus, coincides with embryonic genome activation, which occurs at the late 2-cell stage in mouse embryos. Here (p. 4514), Edgar Vogt, Rüdiger Behr and colleagues investigate the involvement of the pluripotency factor LIN28 in nucleologenesis in mouse embryos. LIN28, which is abundantly expressed in early embryonic tissue, is an RNA-binding protein that can contribute to the reprogramming of somatic cells to pluripotent stem cells. The researchers report that LIN28 accumulates at the periphery of NPBs and mature nucleoli in preimplantation embryos and that initiation of LIN28 expression coincides with embryonic genome activation. Following LIN28 knockdown, they report, most embryos arrest between the 2- and 4-cell stages. Notably, presumptive NPB sites are not enriched with the nucleolar marker nucleophosmin in these arrested embryos. Thus, the researchers conclude, LIN28 is essential for NPB assembly and nucleologenesis during early embryonic development.

 

Touch-sensitive morphogenesis

Contact inhibition of locomotion was first described more than 50 years ago by Michael Abercrombie, who reported that migrating fibroblasts change direction and migrate away from each other when they collide. Although little is known about contact inhibition in vivo, it was recently reported that contact inhibition helps to drive the uniform embryonic dispersal of Drosophila macrophages (haemocytes). Now, Graham Dunn, Brian Stramer and colleagues (p. 4555) mathematically analyse and simulate the contact repulsion dynamics of haemocytes moving along the ventral surface of the Drosophila embryo to investigate the involvement of contact inhibition in the patterning of haemocyte movements. Their simulation, which they test experimentally, reveals that the final pattern of haemocyte distribution, as well as the timing of pattern formation, can be explained by contact inhibition dynamics within the geometry of the Drosophila embryo, irrespective of external cues. This finding has broad implications for morphogenesis because it suggests that contact inhibition of locomotion can be a significant driving force for embryonic pattern formation.

 

PBAP sets the (chromatin) boundaries

The establishment of chromatin boundaries (transcriptional regulatory elements that counteract the spreading of silent chromatin) is essential for proper development. At these boundaries, the histone variant H3.3 replaces H3.1 in a process that, in Drosophila, involves the sequence-specific DNA-binding protein GAGA factor, the chromatin remodelling complex FACT, and the H3.3-specific chaperone HIRA. The H3.3 replacement is also likely to require an ATP-dependent remodelling factor and, on p. 4582, Susumu Hirose and colleagues identify this factor. The researchers show that GAGA factor associates with the Polybromo-associated Brm (PBAP) remodelling complex, which consists of several Trithorax group proteins, and recruits it to chromatin boundaries in Drosophila. They further show that mutations in GAGA factor, Brm and Polybromo/Bap180 disrupt H3.3 replacement and boundary function in a synergistic manner. Moreover, PBAP is needed to generate a DNase-hypersensitive site at the d1 chromatin boundary and HIRA reverses this alteration. Based on these results, the researchers propose a model for H3.3 replacement at chromatin boundaries.

 

Notch muscles in on myogenesis

The capacity of stem cells to generate successive classes of committed progeny during development has been well-studied in some systems but is largely undefined for many tissues. Now, on p. 4536, Shahragim Tajbakhsh and co-workers investigate the role of Notch in the temporal specification potential of mouse skeletal muscle stem cells. The researchers show that Notch is active throughout development in the muscle founder stem cell population, and that expression of activated Notch (NICD) is sufficient to autonomously maintain self-renewing muscle stem/progenitor cells throughout embryogenesis, despite the absence of committed progeny, which were previously shown to be required for muscle stem cell maintenance. NICD-expressing replicating embryonic stem/progenitors respond to foetal environmental cues as development proceeds. Furthermore, the researchers report, siRNA-mediated silencing of NICD in this population promotes the temporally appropriate foetal myogenic fate, despite the expression of markers for multiple cell types. Given these results, the researchers propose that Notch signalling both maintains muscle stem cells and allows them to be receptive to specification cues throughout development.

 

Plus…

 

The effort to make mosaic analysis a household tool

In another ‘Development Classic’ article, Xu and Rubin describe how they set out to improve the methods used to make genetic mosaics in Drosophila and how these efforts led to their 1993 Development paper.

 

See the Spotlight article on p. 4501

 

Book Reviews

Our final print issue of the year includes our annual Book Review section, which highlights a number of recently published books covering topics ranging from auxin signaling, the extracellular matrix and neuronal guidance, to genomics and, more broadly, the principles that shape life. We’ll post each these Book Reviews on the Node over the coming months, but you can also view them (and reviews from previous years) here.

 

 

 

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Categories: Research

SpotOn London

Posted by , on 20 November 2012

audienceLast week I attended SpotOn London – a conference focused entirely on the role of the Internet on research, science outreach, science policy, tools, and related topics. There were talks about using alternative metrics to asses the value of research papers, discussions about doing outreach while working in the lab, issues related to women in science, workshops about new tools or tips on how to talk to politicians about science. The attendees were all interested in science, but not all of them were researchers. There were people working at tech companies, and writers, and even politicians. It was also a great opportunity to meet people in other fields, and be reminded that everything is different for physicists, for example.

Juggling jobs panelCompared to scientific conferences, SpotOn is much more inclusive. The discussion sessions and workshops were all selected from submitted proposals, but it didn’t matter whether you were a student or a professor, or anyone else – any interesting proposals were assessed at face value. For example, the discussion session about juggling science communication and a research career was proposed and organized by two PhD students (Heather Doran and Jonathan Lawson) and included postdoc and PI panelists who all combine their research life with science communication activities. If you’re interested in this topic, you can watch the entire session here:

Yes, all the talks and discussions were recorded. I also ran one of the discussion sessions, which is somewhat related to the one above. It was on “Stories behind the research” and the panel gave three different perspectives on the role of storytelling in science: Vibhuti Patel works for the Royal Society of Chemistry, a publisher and learned society; Ben Lillie runs The Story Collider, an event/podcast/magazine where people tell stories about science; Anne Osterrieder is half researcher, half science communicator. Between the three of them they covered issues related to finding out what makes a good story, when and where to share what, and why people – researchers as well as others – care about this.

In my intro to the discussion I also showed an example from the Node – this post by Tohru – to show how there can be interesting stories behind a paper that don’t make it into the paper itself, and how you can use blogs (such as the Node) to record those stories where relevant, and even link them to the paper in question. The discussion with the audience was really entertaining (with lots of laughs!), but also informative. There were professional science writers in the audience who said that they had a hard time getting scientists to share more than just the plain basics of the work, and researchers who were reluctant about connecting their work to the human experience of being a researcher. A full report from the “stories behind the research” session can be found on the SpotOn blog and the video is on their media page.

You can find links to all individual session pages (all with video!) here. My summary above is heavily focused on the science communication track and on talks aimed at researchers, because I think that’s what most of you are interested in, but there was a lot more: publishing, crowd-funding research, discovering new tools to manage your lab work, social media at conferences, publishing data, research fraud etc. If any of that sounds interesting, check it out, and come to the conference next year!

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Categories: Education, Events, Outreach, Video