We haven’t posted one of these in a while, but there are quite a few things coming up. Remember to also keep an eye on the calendar, and add events there.

Conference and course deadlines in the next few weeks:
January 14 – abstract submission deadline for the annual meeting of the Dutch Society for Developmental Biology
The meeting is January 30 in Utrecht.

January 18 – abstract submission deadline for the joint meeting of the British Societies for Cell and Developmental Biology
March 17-20 Warwick University
Early registration discount ends February 15.

January 31 – abstract submission deadline for the International joint meeting of the German Society for Cell Biology and the German Society for Developmental Biology
March 20-23 Heidelberg
Early registration discount ends February 15

February 1 – application deadline for the Woods Hole Embryology Course
(This is the course that produces the wonderful images that you’ve seen on the Node and on Development covers.)
June 1 – July 14 2013

Other deadlines:
The deadline to apply for the job of Community Manager for the Node is on January 20.

Less urgent, but worth noting:
Registration will soon* open for the 17th International Congress of Developmental Biology. This meeting is only held every four years, and this year it’s in Cancun, so you won’t want to miss this!

(* I first wrote “January 21st”, but had it mixed up with the JSDB meeting )

(1 votes)

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Abcam is a leading web based business supplying research tools to life scientists worldwide. Our head office is in Cambridge (UK), we also have offices in Bristol (UK), Cambridge, Eugene and San Francisco, (USA), Tokyo (Japan), Hong Kong and Hangzhou (China).

A position has become available to develop the product portfolio in the Epigenetics and Nuclear Signalling research area.

You will be part of a larger team responsible for identifying and prioritising targets for antibody production at Abcam. You will be key in ensuring the antibodies produced receive the highest level of validation and data using both internal and external resources. The role will focus on investigating key topics within the field of Epigenetics and Nuclear Siganalling and driving antibody production to meet customer needs. The ideal candidate will be flexible, work well in a team, be comfortable working to deadlines, prioritising different tasks and have good attention to details. Excellent communication skills are essential. You will have contacts within the scientific community and be confident networking to establish new links. Research experience in the field of Epigenetics, Chromatin or Nuclear Signalling is essential.

This position will provide an exciting opportunity for a motivated individual with a PhD or significant research experience who is looking to make the step into a more commercial environment. All relevant training will be provided.

Key Responsibilities:
i) Develop a strategy to identify new targets for antibody production in the field of Epigenetics and Nuclear Signalling. Prioritise production of the most commercially and scientifically valuable antibodies
ii) Post-production validation and characterization of existing antibodies using both internal and external resources.
iii) Networking with the scientific community to identify unmet needs and new product opportunities for Abcam
iv) Providing scientific guidance and input to troubleshoot production or QC issues for key products, working closely with our laboratory and other members of the team
v) Identify current and upcoming scientific topics in order to provide data/information to the Marketing department, including but not limited to, topics for marketing literature, scientific meetings, top selling products.

Our culture is one that empowers individuals, with responsibility given at an early stage. We place great emphasis on knowledge and experience. The working environment is fun and fast-paced, with everybody working together as a team to deliver great service and the best products to our customers. In addition to competitive salaries we can offer an attractive flexible benefits package which includes a profit-share scheme and share options.

To apply, or for more information please follow this link and submit your CV and cover letter: http://hire.jobvite.com/j/?cj=ozd0Wfws&s=The_node

(No Ratings Yet)

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Here at Development, we’re delighted to welcome François Guillemot to the team of academic editors. François will be replacing Alexandra Joyner, who is soon to step down as our neurodevelopment expert. François heads up the Division of Molecular Neurobiology at the National Institute for Medical Research in London, and his research focuses on the regulation of neurogenesis in the mouse forebrain.

I’d like to take this opportunity to thank Alex for her dedication to and enthusiasm for the journal over the last five years, and to welcome François on board. Given that they used to work together, it should be a seamless transition!

(3 votes)

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A Postdoctoral Fellow position is available in my laboratory.

The overall goal of our laboratory is to understand the cellular and molecular basis of vertebrate organogenesis. Our primary focus is on the elucidation of the mechanisms that govern fate decision and cellular plasticity within the endoderm, for example between pancreas and liver. Toward this aim we perform comparative studies using both amphibian and mammalian model systems, including mouse models and embryonic stem cells.

This position seeks a highly motivated individual with a strong interest in developmental biology. Successful candidate should have a recent Ph.D. or M.D./Ph.D. degree, with strong expertise in one or more of the following areas: genetics, cell and molecular biology, and biochemistry. Prior experience with mouse models and ES cells is a plus. The applicant should be independent and collaborative to be part of a young team and be available for an interview.

Please send your CV, a brief description of your research, and contact information of three references to:

FRANCESCA M. SPAGNOLI, MD PhD

Laboratory of Molecular and Cellular Basis of Embryonic Development
Max Delbrück Center for Molecular Medicine
Robert-Rössle-Str. 10
13125 Berlin
Germany
francesca.spagnoli [a] mdc-berlin.de

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Why did you incubate that sample for 16 hours? Because you wanted to go home for the day – but that much detail is not in your paper! Last night, a few scientists on Twitter started sharing their “overly honest methods”, and today the #overlyhonestmethods hashtag exploded with lots of funny and true stories about scientific experimentation. There are thousands of tweets, still coming in, so I can’t show you all of them, but here is a selection of some of my favourites:

(9 votes)

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Here are the research highlights from the current issue of Development:

Directed differentiation: Nodal steps forward

The directed differentiation of pluripotent stem cells into endodermal derivatives, including insulin-producing pancreatic β cells, has considerable clinical promise in cell replacement therapies. The first step in this process is the conversion of pluripotent stem cells into definitive endoderm (DE). Here (p. 675), Douglas Melton and colleagues investigate the endodermal populations generated from mouse embryonic stem cells treated with Nodal (which is required for in vivo development of DE) or Activin A (which is thought to mimic Nodal activity). These TGFβ family members use the same signalling pathways but, although the researchers show that Nodal- and Activin-derived DE cells have similar gene expression patterns, Nodal-derived endoderm contributes much more efficiently to embryonic endoderm upon transplantation into the gut endoderm of mouse embryos. Importantly, this functional difference between Nodal- and Activin-derived endoderm extends to the subsequent development of pancreatic progenitors in vitro and maturation into insulin/c-peptide-expressing cells in vivo. These data provide a firm basis for the derivation of insulin-producing cells for disease modelling and cell therapy.

Unpaired Sox17 models biliary atresia

Congenital biliary atresia is an incurable disease of newborn infants that is characterised by deformation of the gallbladder and biliary duct system. Yoshiakira Kanai and co-workers now report (p. 639) that haploinsufficiency of Sox17 in C57BL/6 background mice provides a genetic model for this poorly understood condition. The researchers show that SOX17, a transcription factor that is required for definitive endoderm development in various vertebrate species, is expressed at the distal edge of the gallbladder primordium during gallbladder and bile duct development. In Sox17^+/− C57BL/6 embryos, cell-autonomous defects in the proliferation and maintenance of the gallbladder/bile duct epithelia lead to epithelial cell detachment from the luminal wall, bile duct atresia (blockage), bile leakage and inflammation in the bile ducts and liver at late foetal stages. These results suggest that SOX17 has a dose-dependent function in the morphogenesis and maturation of gallbladder and bile duct epithelia during late organogenesis and provide new insights into the pathogenesis of congenital biliary atresia.

Embryonic DNA methylation without Dnmt3L

During embryogenesis and gametogenesis, the DNA methyltransferases Dnmt3A and Dnmt3B establish the genome-wide methylation patterns that are essential for mammalian development and reproduction. The catalytically inert Dnmt3-like (Dnmt3L) is known to regulate de novo methylation in the germline but does it function in the early embryo? Déborah Bourc’his and colleagues have been investigating this question and, on p. 562, they report that, although mouse embryos initially contain a maternal store of Dnmt3L, the protein is rapidly degraded. The researchers show that zygotic Dnmt3L deficiency slows down the rate of de novo methylation in the embryo by affecting methylation density at some, but not all, genomic sequences. Importantly, however, Dnmt3L is not strictly required for de novo methylation in the embryo because methylation patterns are eventually established in its absence, possibly through upregulation of Dnmt3A. De novo methylation can therefore be achieved in vivo without Dnmt3L, which suggests that early mouse embryos are more plastic than the germline in terms of how they acquire de novo methylation patterns.

Mending a broken heart

Human hearts do not regenerate after a heart attack because adult mammalian cardiomyocytes proliferate poorly in response to injury. By contrast, zebrafish regenerate heart muscle after trauma by inducing cardiomyocyte proliferation. Studies of zebrafish heart regeneration might, therefore, identify ways to repair damaged human hearts. Here (p. 660), Wen-Yee Choi and co-workers develop a surrogate model for zebrafish heart regeneration that uses fluorescent ubiquitylation-based cell cycle indicator (FUCCI) technology to visualise cardiomyocyte proliferation in live zebrafish embryos. The researchers generate transgenic lines in which heart-specific promoters drive the expression of G₁ and S/G₂/M FUCCI probes and use these lines to identify several small molecules that alter cardiomyocyte proliferation during heart development. These molecules act via the Hedgehog, IGF or TGFβ signalling pathways, they report. Moreover, the researchers show, the same pathways are activated in regenerating zebrafish cardiomyocytes, and their pharmacological manipulation alters cardiomyocyte proliferation during adult heart regeneration. Future use of this new screening system may identify molecules with the potential to improve human heart regeneration.

Eyeing up proneural bHLH factors

During retinal development, seven retinal cell types are specified from a common pool of retina progenitor cells (RPCs). Several proneural basic helix-loop-helix (bHLH) transcriptional regulators, including Atoh7 and Neurod1, direct the intrinsic programming of RPCs but how do individual bHLH factors influence RPC fate? On p. 541, William Klein and colleagues ask whether replacing one bHLH gene with another redirects the fate of RPCs. Previously, the researchers showed that Neurod1 can replace the function of Atoh7 in specifying retinal ganglion cells (RGCs), which suggests that Atoh7-expressing RPCs are pre-programmed to produce RGCs. Now, they report that insertion of Atoh7 into the Neurod1 locus reprogrammes Neurod1-expressing RPCs, which normally produce amacrine and photoreceptor cells, into RGCs. Thus, Atoh7 acts dominantly to specify an RGC fate. The researchers also identify an Atoh7-dependent enhancer within its target gene Nrxn3 that is used by Atoh7 but not by Neurod1 in the developing retina. Together, these results provide new insights into the specification of retinal cells by proneural bHLH factors.

Body elongation goes with the flow

The tailbud is the posterior leading edge of the growing vertebrate embryo. Now, by measuring the three-dimensional cell flow field of the zebrafish tailbud, Scott Holley and co-workers reveal a posterior flow within the tailbud that reflects ordered collective cell migration (p. 573). They identify a transition in tissue fluidity at the tailbud tip where there is a decrease in the coherence of the cell flow but no alterations of cell velocities. Inhibition of Wnt or Fgf signalling reduces the coherence of the flow, but affects trunk and tail extension differently. By using computer simulations to interpret these complex phenotypes, the researchers show that a decrease in the coherence of the flow combined with a normal flow rate leads to a ‘traffic jam’ in the posterior tailbud and a severely contorted trunk, whereas decreases in both coherence and flow rate merely ‘kink’ the tip of the tail. Thus, the balance between flow rate and the coherence of collective migration within the tailbud steers zebrafish body elongation.

PLUS…

Transcriptional repressors: multifaceted regulators of gene expression

Although classic repressors undoubtedly silence transcription, genome-wide studies show that many repressors are associated with actively transcribed loci. Reynolds, O’Shaughnessy and Hendrich review this evidence and propose that the modulation of gene expression by co-repressor complexes provides transcriptional fine-tuning that drives development. See the Review on p. 505

Establishing and maintaining gene expression patterns: insights from sensory receptor patterning

Rister, Desplan and Vasiliauskas review the mechanisms that generate and maintain sensory receptor expression patterns and compare them to those that control sensory receptor expression patterns in the mouse retina and in the mouse and fly olfactory systems. See the Primer article on p. 493

Click here to see other articles in the ‘Development: The Big Picture’ series.

Radial glia – from boring cables to stem cell stars

As part of the ‘Development Classics’ series, Malatesta and Gotz look back at their 2000 Development paper, in which they showed that radial glial cells act as neural stem and progenitor cells in development – a discovery that has led to a change in the concept of neural stem cells in the adult brain. See the Spotlight on p. 483

A germline-centric view of cell fate commitment, reprogramming and immortality

At the recent EMBO/EMBL symposium ‘Germline – Immortality through Totipotency’, researchers discussed the mechanisms that establish and control totipotency, with an eye towards the mechanisms that may endow germ cells with the ability to propagate totipotency across generations. See the Meeting Report by Torres-Padilla and Ciosk on p. 487

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A postdoctoral position is available in the laboratory of Dr. Sophie Astrof to study roles of cell-extracellular matrix interactions in cardiovascular development and disease using mouse model system. The research will involve investigation of the role of extracellular matrix in orchestrating signaling/communication between various progenitor cell populations during morphogenesis of the aortic arch arteries.  In our lab, we use genetics, conditional mutagenesis, and transgenic approaches to explore roles of tissue microenvironment during organogenesis and disease. Experience with genetic manipulation, embryology and cell biology is desirable.  My laboratory is a part of the Center for Translational Medicine at Jefferson Medical College (http://www.tju.edu/jmc/medicine/translational_medicine/faculty/astrof.cfm?detail=0) located in the heart of Philadelphia. To apply, send a letter of interest, CV and names and contact information of three references to sophie.astrof@gmail.com

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Jordan Raff’s recent Biology Open editorial on the future of publishing, posted on the Node, sparked quite a debate in the comments section. Much of that discussion focussed on perceived problems with the peer review system in scientific publishing. Particularly with the rise of journals like PLoS One and BiO, it seems that authors are increasingly dissatisfied with the time and effort – and with the sometimes cryptic decision-making – involved in publishing in more selective journals (journals whose selection criteria include some measure of ‘conceptual advance’ or ‘general interest’). I promised in one of my comments to Jordan’s post to write in more detail about my take on these issues, and what Development is trying to do to alleviate community concerns with the peer review process. So, here goes…

To start with what is perhaps an obvious point: one of the key aims of the peer review process is to improve the submitted paper, and in the vast majority of cases, I think it does just that – the finally accepted version of a manuscript tends to be both scientifically more sound and easier for the reader to understand than the original submission. Importantly, peer review – whether it’s of the more selective or the purely technical kind – provides some kind of quality assurance stamp on a published paper: although erroneous and fraudulent papers do end up being published, I’m sure there are far fewer of them in the public domain as a direct result of the peer review process.

However, that’s not to say that the system is perfect, because it certainly isn’t. Particularly with the rise of supplementary information, it’s all too easy for referees to ask for a ‘shopping list’ of experiments, many of which can be peripheral to the main story of the paper. And all too easy for editors to simply pass on those referee reports without comment – either because they’re too busy to go through the reports in sufficient detail to figure out what the really important points are, or because they don’t have the specialist knowledge to pass those judgments (which, after all, is why we need referees in the first place!). With a few tweaks to the system, we can do better than this.

For a selective journal, which Development unashamedly is, I think the key is to encourage referees to focus their reports on two things:

1. What’s the significance of the paper and why should it be of interest to the journal’s readership?

2. Do the data adequately support the conclusions drawn, or are there additional experiments necessary to make the paper solid?

With clear answers to those two questions in hand, it should be much easier for editors to decide firstly whether the paper is in principle suitable for the journal (spelled out in the answer to question 1), and secondly what the authors need to do for potential publication (the experiments given in response to question 2). It should get rid of that long list of ‘semi-relevant’ experiments (that aren’t really pertinent to q2), and it should make decisions much more definitive. There’s nothing worse than going through 2-3 rounds of extensive revision only for an editor to decide that the paper’s not worth publishing after all (something that, incidentally, Development is good at avoiding: around 95% of papers that receive a positive decision after the first round of review are published in the journal). Having a clearer (and shorter!) list of necessary revisions should help to avoid such situations.

I’m not a radical and I think it’s evolution not revolution of the system that’s required here. But I (and we at Development) do want to improve things. To this end, we’re looking at ways of changing our report form to reflect the aims laid out above. It might seem like a small step, but I genuinely believe that it could be a valuable one in easing the path to publication.

Moreover, I don’t think that the more radical alternatives work – various possibilities have been proposed and tested, but success is thin on the ground. Deposition in pre-publication servers and community commenting works very well in the physical sciences, but not in the biological sciences – as trials by Nature (see here and here) have demonstrated. Post-publication commenting could be a valuable addition to peer review, or even an alternative to it, but it just hasn’t taken off: I just looked at a random issue of PLoS Biology from 2012 and of the 17 papers published, only 3 had comments, none of which were particularly substantial. Open peer review – where referees sign their reports – would be great in an ideal world, but whenever I ask an audience if they’d be happy to sign their report if they were reviewing a paper for a top name in their field who might in turn be reviewing their next grant application, the vast majority opt to stay anonymous. It’s a competitive world out there, and scientists (like everyone else) hold grudges. Double-blind peer review – where the authors are also anonymous – might have some benefits in terms of reducing potential referee or editor bias, but it’s not easy to implement, and in most cases the referees will know who the authors are in any case.

So given the limitations of the alternatives, I believe that most journals will continue to operate some form of traditional peer review for the foreseeable future, and I don’t think this is a bad thing. That’s my opinion, but we also want to hear your views on this. What most frustrates you about the whole publishing process? Would a more streamlined review process like the one I’ve suggested help? What else can we do to make the system better?

Finally, though, there’s one thing that always comes to mind when I hear people complaining about the review process. You as authors are also the reviewers (or if you aren’t yet, then you one day will be) – meaning that you’re the ones giving ‘unreasonable’ lists of experiments to other people. It’s easy to pick holes in a paper, but harder to recognise when the authors have already done enough. So when you put on your reviewing hat, remember how you felt about the anonymous hyper-critical reviewer of your own paper so you don’t risk turning into one of them!

(6 votes)

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Happy New Year!

We’ve looked at our stats for the past year to see which posts were the most popular. At the top of the list were the Woods Hole images and the two essay competition nominees, There’ll be dragons? and An Excitingly Predictable ‘Omic Future.

But there were many other popular posts this past year. The following list includes some of the most-viewed or top-rated posts of 2012. It’s a mixed bag of publishing discussions, research news, career features and pretty images – written by students, post-docs, lab heads, and others. Thanks for another year of great content!

Fast times at MBL (by Andrew Mathewson)

A career in science management (interview with Andrea Hutterer, by Natascha Bushati)

Colouring the mouse embryo (by Michael Wong)

Piecing together the squint puzzle (by Karuna Sampath)
See also her student Shimin’s perspective at New visions from the 3’ end of squint.

Bio Editorial – Publishing in the biochemical sciences: if it’s broken, fix it! (by Jordan Raff)
There’s a lively discussion in the comments of this post that’s also worth a read.

Freeware for scientists (by Nishal Patel)

Photo-morpholinos (by Philip Washbourne)

How obsession can fuel science blogging: the story of Retraction Watch (by Ivan Oransky)

A few older posts still received enough regular visitors to keep them among the most visited of 2012:

Hair follicle stem cells – the hairy truth (by Erin Campbell, posted in 2011)

Turtles in a nutshell (by Bruno Vellutini, posted in 2011)

7th European Zebrafish meeting (by Maria Nicolas Perez, posted in 2011)

The intestinal crypt (video from Hans Clevers’ lab, featured on the Node in 2010)

Is your favourite post missing from this list? These most-viewed and top-rated posts were generally the ones that were emailed around a lot, or shared on social media. If you see something you like on the Node, tell your friends!

(3 votes)

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And we’ve reached the end of another full calendar year on the Node. What were your favourite posts this year? As a refresher, here is a look back on some of the content of this past month.

Advent calendar
For most of this past month, you will have been able to find a new paper each day behind the virtual doors of our advent calendar. A summary of this collection of papers was posted on Christmas morning.

Node news
The Node now has some custom tea bags, which you’ll be able to pick up at various conferences. You can drink the Node tea while reading or writing for the Node. But maybe you want to do more than read, write and drink tea? In that case: come work for us! Eva is leaving at the end of February, so we’re hiring a new community manager to run the Node. It’s a very interesting job with a lot of creative input, and you can apply until January 20.

Open Access Discussion
The post itself is from earlier this year, but in the past weeks a lot of people have been contributing to the discussion on open access publishing in the comments of Jordan Raff’s Biology Open editorial.

Research
We heard about some exciting research this last month of the year. In an interview, Roger Barker talks about an international collaboration studying the generation of medium-sized spiny neurons from stem cells.

“In this particular paper, the group in Italy, led by Elena, have such fabulous expertise in developing striatal neurons, but their lack of access to human fetal material makes it very difficult for them to do the project without collaborating with a lab like ours, in a country that does have access to fetal material. So these are truly international collaborations and without either party the project wouldn’t happen.”

Elsewhere, Martin Jakt writes about his paper on a technique to estimate gene expression within single cells.

“The future brings with it hopes of understanding complex biological phenomena such as embryonic differentiation through computational modelling of the interactions between regulators and regulatees. Such models make predictions of cellular behaviour, which in the case of differentiation of multipotent cells must include the generation of diversity. Methods such as candy FISH allow not only the direct observation of the behaviour of systems at the individual cell level, but also make it possible to take into account effects of interactions between cells thus turning the problem on its head.”

Also on the Node:
–Wikipedia edit-a-thon in Oxford
–New Development book reviews
–Don’t get rid of the middle-man

(1 votes)

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