In a follow up to Eva’s first post in our alternative careers series about how a research background in developmental biology can lead to a career path that lies outside of research, I hope that my description here of how I made the move from a PhD in developmental genetics to a career in publishing will be of use to anyone else out there in the community who is considering making a similar move.

My journey in science began with an undergraduate degree, not in genetics, but in pharmacology at King’s College, London, where the most important thing I learned was that I was much more interested in genetics and development than I was in pharmacology, interests that led me to a PhD with Ian Jackson and Cathy Abbott at the MRC Human Genetics Unit in Edinburgh. From there, I became a post doc in Val Wilson’s lab.

At the time of my PhD, Ian was a regular contributor to the journal club section of Trends in Genetics, and when short on time, he would ask me to write these brief pieces on a paper of interest in his place. I came to enjoy this writing exercise and, as a result of it, was offered other writing opportunities, such as summarizing new mouse knockout phenotypes for a knock out database then under development at BioMedCentral. (In fact, one of the journals I had to check every month for new knock out papers was Development.)

As my fondness for writing grew, another opportunity arose towards the end of my PhD that helped me to choose between the different career paths I was starting to consider: research, science journalism, or a job in science publishing. This opportunity took the form of a Media Fellowship from the British Science Association. These fellowships place British scientists with a media organisation for a couple of months, where they learn to work within the constraints of the media to produce interesting stories about science. I was placed with the Guardian, a national daily newspaper in the UK, where I spent several weeks under the tutelage of Tim Radford,  who was its science editor at the time. Under the guidance of Tim’s red pen, I wrote science-related stories covering a wide range of topics, from archaeological discoveries (see picture), to cancer, and even about why Mozart had such a foul tongue (he had Tourette’s, so the story went). I also had many a story ‘spiked’ by the news desk editor, when it failed to pass the “so what?’ barrier that most science-related stories have to pass. This experience taught me several important things: how to write concisely and engagingly about science; about the constraints that journalists work under; and about the importance of scientists learning to communicate clearly and succinctly with the media about their work. But it also left me a little disheartened about the difficulties of getting good science stories covered, even by a reputable newspaper such as the Guardian, when they have to compete for space with stories about politics, crime and celebrity gossip, all of which have a more tangible ‘human interest’ angle for most news desk editors.

As a BSA media fellow, you write about whatever story is sent your way

As a result, I returned to the lab knowing that a career in science journalism was probably not for me while suspecting that my scientific interests were too broad to remain in research. But first I needed to give research a proper chance because to leave it felt like an irreversible decision not to be taken lightly. I have never regretted my time as a post doc; I learned much about embryology from Val, which has stood me in good stead to this day. My postdoc also broadened my scientific horizons and contacts, while giving me time to learn more about career options in publishing.

In time, I successfully applied for the job of assistant editor at Trends in Molecular Medicine (TMM), having heard good things about the Trends journals while writing for them as a student. I joined the office in Cambridge, which became a training ground for a generation of British editors, many of whom still work in publishing today. From feedback on my application, it became clear that I was offered this post because my CV showed that I was demonstrably interested in writing and in science communication; skills that complemented my role on TMM, where I assisted with developmentally editing reviews and was responsible for copyediting the content of the journal, while occasionally writing news stories for its front section and being dispatched to do live conference reporting for BioMedNet. It was a great first job in publishing, but not, as I subsequently discovered, what I really wanted to be, which was a commissioning editor. And so within a year of being recruited to TMM, I successfully applied for the role of Editor of Trends in Genetics, where I began to learn properly, for the first time, the job of a commissioning editor.

I have at heart been a commissioning editor ever since. In science publishing, a commissioning editor’s job is to determine the content of a journal, book or journal section and then to invite people – such as scientists, science writers and commentators, to write for their publication. The commissioning part of the job requires an editor to travel widely to conferences and to keep in close contact with their field, so that they can identify the topics that are the hottest and most interesting to commission articles on. The editorial part of the job comes in developmentally editing articles to improve their focus, structure, scientific content and accessibility and in making editorial decisions about whether a manuscript should be revised, accepted or rejected in response to the reviewers’ and your own editorial assessment of it.

My own experience as a commissioning reviews editor was further strengthened when I moved from Trends in Genetics to Nature Reviews Genetics,where I joined Mark Patterson and Tanita Casci to launch NRG as one of the first Nature Reviews journals. Launching NRG was a hugely exciting project that taught me not only a fantastic amount about genetics from working with Mark and Tanita and our many great authors, but also how to launch a journal from scratch. When Mark stood down as Editor in Chief of NRG, I successfully applied for this role and from this position moved to Development: my first experience at managing a primary research (and not-for-profit) journal.

My signed copy of the launch issue of NRG

As Executive Editor of Development, I wear many hats: I manage the in house journal team, and commission and handle reviews and other front section articles, together with Seema Grewal, the journal’s associate reviews editor. I also work closely with Development’s Editor in Chief, first Jim Smith and now Olivier Pourquie, and our team of dedicated scientific editors in handling papers and author queries, and in developing the journal editorially. I am also responsible for the journal’s online presence. And in response to a Development readers’ survey in 2009, I kick started another new and exciting launch project that, once we had Eva on board, came to fruition as this: the Node, which I had the honour of naming.

Being a managing and commissioning editor is a highly interesting and rewarding role. As an editor, you learn about new scientific findings every day and have to assimilate a lot of new information quickly, and you work within a wider community, building sometimes long-standing relationships with researchers, authors and reviewers. I’m particularly fortunate in having the developmental community to work with, a community I’ve found to be tremendously collegial. And, occasionally, I’m asked to do other fun things, such as speaking at meetings about publishing and interviewing speakers at the CSHL symposia.

Getting that first foothold in publishing is by far the hardest, most competitive step of all. I was successful in making this initial move by being able to demonstrate my enthusiasm for writing about and communicating science, and by having gained experience while still in research that significantly strengthened my application for my first editorial job. Other Editors, particularly primary manuscript editors who mainly handle research papers, may  have taken different paths from research to publishing, and it’s our hope that they will also share those different career paths and their experience with you here on the Node.

(8 votes)

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The Node’s staff has kindly given me the opportunity to write a background piece, placing into context the results of our studies described in the paper, “Sox9⁺ ductal cells are multipotent progenitors throughout development but do not produce new endocrine cells in the normal or injured adult pancreas” (released today in Development; http://dev.biologists.org/lookup/doi/10.1242/dev.056499).

For many years, debate has raged in the pancreas biology field as to the source of new insulin-producing beta cells in the adult pancreas, both in healthy and injured states. This is a topic of great interest as many groups around the world are engaged in the quest to repopulate functional beta cell mass in diabetic patients, either through transplantation of hESC/iPSC-derived beta cells, or by stimulating growth of residual beta cells in such patients. Manipulating endogenous pathways of beta cell regeneration, should they exist, might prove to be one avenue of curing diabetes. Thus, this is a hot-button topic.

In 2007, when I joined Dr. Maike Sander’s laboratory, the diabetes field was heatedly pursuing the question of whether or not new beta cells can arise from pancreatic ducts. The possibility that ducts might harbor facultative progenitor cells capable of producing beta cells upon stimulation energized many labs to do experiments to test this theory.  All of this attention was mainly due to studies that observed beta cells closely juxtaposed to pancreatic ducts after pancreatic injury (Gu et al., 1994). This was complemented by exciting data showing that Ngn3, an endocrine progenitor marker, is re-expressed in the ductal epithelium of beta cell regenerative models, such as partial duct ligation (PDL) (Xu et al., 2008). Yet another study, published by Rovira and colleagues, demonstrated that cells at the very end of the ductal tree (centroacinar/terminal duct cells) could be isolated from mice and behave like progenitors cells in the dish as well as differentiate correctly in an embryonic environment (Rovira et al., 2010). These findings all pointed to pancreatic ductal cells as a source of new pancreatic beta cells. That is until groups started to create and test CreER mouse lines with expression specifically in ductal cells (Furuyama et al., 2010; Kopinke et al., 2011; Kopinke and Murtaugh, 2010; Means et al., 2008; Solar et al., 2009) in the hopes of tracing duct-derived beta cells. I am a part of one of those groups.

Sox9creER labeled pancreatic ductal tree

In our group, we created a Sox9-driven CreER^T2 BAC transgenic mouse line and were thrilled to find that we could efficiently and exclusively label the pancreatic ductal tree in the adult Sox9CreER^T2;R26R^LacZ mouse (show picture). Given that the Sox9CreER^T2 transgene labeled such a large percentage of ductal cells (~70%), we felt confident that if any beta cells arose from the ductal compartment after PDL, we would be the group to detect it. Therefore, I teamed up with Claire Dubois, a graduate student in Dr. Sander’s laboratory, to perform PDL on tamoxifen-injected Sox9CreER^T2;R26R^YFP mice. As predicted by Xu et al. (2008), we observed a large increase in Ngn3 mRNA in the ligated pancreatic lobe and a low signal for Ngn3 expression was found in duct-like foci derived from Sox9⁺ ductal cells after PDL. Much to our surprise though, PDL did not induce the production of new beta cells from lineage-labeled ductal cells. This suggests that Ngn3 expression is initiated in Sox9⁺ cells after PDL, but the presence of Ngn3 is not sufficient to initiate endocrine differentiation. Therefore our findings and the majority other studies published thus far do not support the hypothesis that adult pancreatic ductal cells contribute to the endocrine compartment during normal aging or after PDL.

Because many studies, including our study published today, agreed that acinar cells are maintained by self-replication and are not produced by other cell types (Desai et al., 2007; Jensen et al., 2005), I had focused on the question of endocrine neogenesis in the pancreas. However, Furuyama and colleagues recently created a knock-in Sox9^IRES-CreERT2 mouse line and showed that Sox9⁺ cells can produce acinar, but not endocrine cells, in the adult mouse (Furuyama et al., 2010). How do we explain the discrepancy between their findings and ours? While we don’t fully understand the reason, small, but possibly significant, differences in the experimental design could provide an explanation. The tamoxifen doses used by Furuyama and colleagues were extremely high and resulted in labeling of acinar cells upon tamoxifen administration. Likewise, we observed patchy acinar cell labeling with our highest dosage of tamoxifen. It is possible that acinar cells express Sox9 at low levels, but recombination only occurs when the concentration of tamoxifen reaches a certain threshold. However, with the tamoxifen dosages used in our study the percentage of labeled acinar cells did not increase during the chase period. As it is unclear how long CreER remains active after very high dosages of tamoxifen, it is possible that rather than arising from Sox9⁺ ductal cells, in Furuyama’s study acinar cells are continuously labeled for an extended period of time after the tamoxifen pulse. Thus, additional studies showing results similar to those of Furuyama et al. will be necessary before it can be concluded that ductal cells contribute widely to the production of acinar cells.

Does this mean that ductal cells are not capable of producing other pancreatic cell types? The ability of ductal cells to form endocrine and acinar cells during development and the ex vivo analysis of terminal duct/centroacinar cells (Rovira et al., 2010) would suggest that ductal cells can be multipotent under the right circumstances. Therefore, future comparisons of the embryonic and adult ducts, as well as their microenvironments, may provide the key to turning a duct cell into an acinar or beta cell.
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(8 votes)

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Is this Monday not quite giving you the results you were hoping for? Cheer up with a few science music videos.

This one, “Bad Project”, is being emailed around rapidly among scientists worldwide, so there’s a good chance you’ve already seen it. If not, it’s worth a watch for the costumes (made of lab supplies!) and dance moves alone.

The next video is a bit older, but a lot more positive about research, and an ode to a famous evo devo model organism.

Both videos were products of departmental science variety shows or contests. “Bad Project” was a submission for a Molecular and Human Genetics Retreat 2011 at Baylor College of Medicine, and “Bringin’ Stickleback” was a submission for the 2009 “MCB Follies” at the Department of Molecular and Cell Biology at UC Berkeley).

Have any of you ever made a video (music or otherwise) with or in your labs? Would you like to? (Asking for a reason, so please do share your thoughts. I’m looking at you, students and postdocs. You there, with your eye on the lab timer, reading the Node while waiting for your experiments… Have you ever filmed something in your lab?)

(5 votes)

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A friend of mine went straight from his PhD in computational (pharmaco)chemistry to an investigator position, and I have heard an unconfirmed second-hand story of one other person recently making this transition in a life science related area. But by and large, most PI jobs require that you have done at least one postdoc, and the suggestion of people skipping this stage entirely seems like an urban myth. Historically, however, a PhD degree is itself enough for an academic position, and in several fields (most notably the humanities) this is still the case.

By requesting applicants to do one or more postdocs, the need for them is propagated further, but the NIH is now trying to break the mold by introducing a grant specifically meant to skip your postdoc. They describe it as follows:

“Although traditional post-doctoral training is likely most appropriate for the majority of new Ph.D.s and M.D.s, there is a pool of talented young scientists who have the intellect, scientific creativity, drive and maturity to flourish independently without the need for traditional post-doctoral training. Reducing the amount of time they spend in training would provide them the opportunity to start highly innovative research programs as early in their careers as possible. “

Of course, this still requires them to find an institute that will hire them without the ubiquitously desired “postdoctoral research experience”, but arriving at the door with an NIH grant under your belt should help.

The deadline for this new grant is this Friday. Are any of you applying? What do you think of this idea? Let us know via the poll below.

(poll closed and archived)

(2 votes)

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The conference website is here and is accepting abstracts until February 7th, 2011. It will be in English.

There is a good roster of speakers and it should be a stimulating occasion for those of us in Europe with the time and money to spend a few days in April in Paris.

(1 votes)

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Hot off the press from the holidays is an article from PNAS that’s worth a gander if you’re into RNAi. We know RNAi associated with epigenetics is possible in the nucleus (Somehow, siRNAs could trigger the methylation and silencing of genes in the nucleus.) However, one soy bean group was able to provide evidence for mRNA slicing in the nucleus.

RNAi is becoming relevant in soy oil production. If certain genes are down regulated, they can reduce the poly-unsaturated fatty acids content levels by 65% (a higher level of saturated fat instead of unsaturated could increase the heat capacity of oil, making it better for deep fries). However, many genes are involved in fatty acid production. Some are from the same family and are highly similar in sequence. To focus on one family member, Hoffer et al. produced an siRNA directed against unique sequences in the intron (perhaps expecting some epigenetic silencing).

Typically, all data pointed to the main mechanisms of RNAi taking place in the cytoplasm, where all the action of mRNA takes place. siRNAs and other small fry had to be shuttled from the nucleus to the cytoplasm. There they would regulate the mRNAs either by slicing them or blocking protein synthesis.

So, it came as a surprise when Hoffer et al. found accumulation of siRNAs against the intron sequence in their targeted mRNA. They were also able to detect sliced up target pre-mRNA. It’s unusual since generally intronic sequences are spliced out of mRNA before transport to the cytoplasm. It could mean that siRNAs can be directed against immature mRNAs in the nucleus. Potentially, this would be another way of attaining further specificity of RNAi. However, levels of the fatty acids were reduced to 20%, so it may not be efficient as cytoplasmic silencing.

Not a whole lot of research has been done on RNAi in the nucleus. So we don’t particularly know much about the active siRNAs that accumulate there. Were they produced in the nucleus and then active at RNAi straightaway? Or were they transported back from the cytoplasm? A worm study isolated an Argonaute protein that transports siRNAs from the cytoplasm into the nucleus. One in mammalian cells has shown that some miRNAs have sequences that can direct them to the nucleus.

Evidently, RNAi in nucleus could have potential in increasing its specificity for a single target. Many genes, especially those from the same family, have high homology (sequence similarity). If even intronic sequences of an mRNA can be targeted, it’s more to choose from.

It’s also a bit like finding out that penguins aren’t just indigenous to the Arctic/Antarctic. You can find native species in South Australia & New Zealand. I had no idea that there are wild penguins in Australia, but  there they are. (Flikr CC, M Kuhn)

*In their analyses, the authors fractionated cells into nuclear and cytoplasmic samples and looked at the accumulation of siRNAs and target mRNA transcripts. They were able to detect an accumulation of siRNAs specificity to intron and exon spanning regions. As well, they found a lower level of mRNA transcript in the nucleus than in the cytoplasm. Normally you would expect the reverse, as mRNAs are usually sliced up in the cytoplasm. Via blotting, they were also able to show an accumulation of sliced up mRNA transcripts in nuclear fractions.

Using reporter genes, they then looked for RNAi proteins responsible for producing siRNAs in the nucleus. They could see nuclear localization for the two proteins analyzed: RDR6 (reverse transcribes RNAs) & Dicer Like proteins (excises dsRNA into siRNAs). What would be more interesting, however, is if they looked at the effector proteins of mRNA slicing, the Argonautes.

Hoffer, P., Ivashuta, S., Pontes, O., Vitins, A., Pikaard, C., Mroczka, A., Wagner, N., & Voelker, T. (2010). Posttranscriptional gene silencing in nuclei Proceedings of the National Academy of Sciences, 108 (1), 409-414 DOI: 10.1073/pnas.1009805108

Guang, S., Bochner, A., Pavelec, D., Burkhart, K., Harding, S., Lachowiec, J., & Kennedy, S. (2008). An Argonaute Transports siRNAs from the Cytoplasm to the Nucleus Science, 321 (5888), 537-541 DOI: 10.1126/science.1157647

Heinrichs, A. (2008). Gene expression: Argonaute on the move Nature Reviews Molecular Cell Biology, 9 (9), 666-666 DOI: 10.1038/nrm2473

Hwang, H., Wentzel, E., & Mendell, J. (2007). A Hexanucleotide Element Directs MicroRNA Nuclear Import Science, 315 (5808), 97-100 DOI: 10.1126/science.1136235

(1 votes)

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I just got back from attending two meetings about academia and the internet – one in person and the second, in true internet style, virtually. Both meetings at one point or another discussed the growing trend toward archiving and citing data itself (on top of citing the papers written based on analysis of the data).

The first meeting was the HighWire publishers meeting. HighWire takes care of the online version of many journals, including Development, and their meeting was mostly about practical things for journals and not directly relevant to most of you yet. (You can still find some of the discussion on Twitter, although Twitter’s search function expires after about 10 days.)

The second meeting, which I followed over the web, was Science Online in North Carolina. That meeting is now in its fifth year, and started out as a meeting solely about science blogging, but has expanded to cover other aspects of science and the internet.

It was rather interesting to follow both meetings back to back, since the first was very practical and aimed at things that publishers can do and are doing right now, while the second was full of thoughts and ideas and the audience was very varied. There is still a lot of science blogging being discussed at the Science Online meeting, and I myself Skyped into a panel with 15 community managers of different science blog networks. (“Different” is the keyword here, because the Node has very little in common with, say, the Guardian or Discover blog networks, but it was interesting to hear some comparisons.)

A few topics, however, came up at both the HighWire meeting and at Science Online, and one of these was the new problem of citing data. As Benoit mentioned here back in August, the Journal of Neuroscience no longer publishes supplementary data. This journal was at the HighWire meeting to share how that is going so far, and one of the surprising reactions they had was a response from librarians: If journals don’t publish supplementary data, it has to go somewhere, and libraries are stepping up to claim the niche of data archiving and curating. The J. Neurosci. talk was followed by a librarian from Stanford who mentioned that they just hired a “data librarian” to look into things like this.

And they’re not the only ones: last fall at the Science Online London meeting, the British Library showed that they were very involved in data archiving as well. And as I mentioned, this weekend’s Science Online North Carolina meeting also included a few talks about data archiving and whether having your data cited will one day be valuable for your career (just like having your papers cited is now).

What do you think of this movement toward archiving and citing data? Are you happy that you’ll be able to find other people’s data? Annoyed that it’s yet another thing to keep on top of? And where are all your data at the moment? Can someone easily find them if they want to build upon your work? Have you ever cited a database in a paper?
(more…)

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Two postdoctoral positions are available in Jim Smith’s lab at the National Institute for Medical Research in north London. One is is supported by the Leducq foundation, under a multidisciplinary programme designed to elucidate the role of bone morphogenetic protein (BMP) signalling in the pathogenesis of pulmonary and systemic vascular diseases. The work will use zebrafish embryos to study the activation and roles of BMP target genes identified by high-throughput sequencing. Further details, including salary and how to apply, are available at http://www.nimr.mrc.ac.uk/jobs/IRC11806/.

The second position will continue the laboratory’s work on evolutionary aspects of the genetic regulatory network that underlies mesoderm formation. The work will use Xenopus and zebrafish embryos and human and mouse ES cells as appropriate. Further details, including salary and how to apply, are available at http://www.nimr.mrc.ac.uk/jobs/IRC11805/.

The closing date for both positions is February 14, 2011. Informal enquiries can be made to Jim Smith (jim.smith@nimr.mrc.ac.uk).

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Post doctoral position available to study the neural crest gene regulatory network (NC-GRN) in Xenopus and zebrafish. Neural crest cells are stem cell-like progenitors that migrate extensively and are essential to the establishment of the vertebrate body plan. Misregulation of components of the NC-GRN underlies numerous human diseases and congenital disorders. Studies involve post-translational regulation of known network components, and use of proteomics and next generation sequencing to identify novel components.

Highly motivated applicants with a PhD and strong background in cell and molecular biology and/or developmental biology are encourage to apply. Please send a CV, brief description of research interests, and the names of three references to:

Carole LaBonne, PhD (clabonne@northwestern.edu)
Department of Molecular Biosciences
Northwestern University, Evanston, IL 602028

Northwestern University’s main (Evanston) campus is on the shores of Lake Michigan, close to the heart of Chicago, one of the most beautiful and culturally rich cities in the US.

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Applications are invited for a PhD studentship investigating cell differentiation during development (closing date 14th January, 2011).

Cell differentiation programmes are central to the production of specialised tissues during development. Moreover, in-depth understanding of cell differentiation is essential for many applications, including stem cell technology and tissue repair. We study the programme that governs muscle formation. This is important not only because muscle is a major cell type and an established paradigm for cell differentiation, but also because of its significance for human health. You will analyse the control of when and where muscle differentiation occurs and how this differentiation programme is orchestrated. You will use the classic, genetically tractable, model organism Drosophila melanogaster, which has shaped much of our understanding of animal development and has an impressive history of informing human biology and medicine. You will analyse the differentiation of both embryo and adult progenitor cells, the latter in remodeling and regeneration during metamorphosis.

Progenitor cell differentiation is controlled by a balance of factors. A key promoting factor for muscle is the conserved Mef2 transcription factor. We found that expression of different muscle genes requires different levels of Mef2 activity (PNAS 105:918-923 (2008)). This highlights the importance of understanding how Mef2 activity is regulated, which is the focus of this project. We also recently identified a novel regulator, Him, that down-regulates Mef2 activity and inhibits muscle differentiation (Current Biology 17:1409-13 (2007)). You will analyse both Him and other Mef2 regulators, including those identified in an ongoing screen, and also assess Mef2 activity during muscle differentiation using in vivo Mef2 sensors. Together, this will indicate how Mef2 can co-ordinate the expression of diverse muscle genes and unravel mechanisms that maintain progenitor cells in an undifferentiated state.

The host lab in the School of Biosciences, Cardiff University offers valuable training possibilities through interactions with labs across Europe and the opportunity to use a broad range of techniques from molecular cell biology and genetics.

Interested candidates should send a CV and statement of research interests to Dr Mike Taylor (TaylorMV@cardiff.ac.uk) as soon as possible. You must also apply formally on-line by following the details at http://www.cardiff.ac.uk/biosi/degreeprogrammes/postgraduateresearch/index.html.

Informal enquiries are welcome. Please email Dr Mike Taylor at TaylorMV@cardiff.ac.uk or telephone on +44 (0)29 208 75881.

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