Here are the highlights from the current issue of Development:

Atoh1: earmarked for differentiation

Atoh1 is a key regulator of the differentiation of hair cells, the sensory cells that support audition: it is upregulated during their differentiation and downregulated at postnatal stages. But what are the mechanisms underlying Atoh1 transcriptional regulation during inner ear development? To address this question, Neil Segil and co-workers (p. 3529) analysed the epigenetic status of Atoh1 in mouse hair cell progenitors. They report that histone H3 at the Atoh1 locus is bivalently marked by the repressive tri-methylation of lysine 27 (H3K27me3) and the permissive tri-methylation of lysine K4 (H3K4me3). In nascent hair cells, Atoh1 upregulation is accompanied by a reduction in H3K27me3 and requires the appearance of the permissive acetylation of histone H3 lysine 9. At postnatal stages, Atoh1downregulation is achieved by an increase in H3K9me3, which is a mark indicative of transcriptional silencing, and a reduction in histone H3 acetylation. In early postnatal supporting cells (a cell population that separates and surrounds hair cells and can regenerate them during the first postnatal week in mice), the bivalent marks are maintained, potentially explaining their latent regenerative capacity. This study suggests a mechanism for the epigenetic control of Atoh1 levels during inner ear development and reveals a potential target for future regenerative efforts to replace mammalian hair cells.

Revisiting blastomere equality

The fertilised mammalian egg gives rise to seemingly equivalent blastomeres until the fourth cleavage division, when the first indication of lineage specification appears. At this point, certain blastomeres divide symmetrically and others asymmetrically. When do these apparently identical cells diverge and how do these differences arise? To answer this question, Enkui Duan and colleagues performed single-cell transcriptional analysis of human and mouse blastomeres (p. 3468). By studying the mammalian zygote, in which transcription – a known source of heterogeneity during mitosis – is mostly silent, the authors showed that small biases in gene expression arise after the first cleavage division from the unequal distribution of cellular substances between daughter cells, called ‘partitioning errors’. These are especially pronounced for transcripts present in small quantities, which are more likely to be asymmetrically distributed. As cleavage divisions progress, the activation of embryonic transcription minimizes or amplifies the initial biases through positive or negative feedback regulation. Furthermore, the authors show that lineage specification is driven by the relative ratio of pairs of competing lineage specifiers, such as Cdx2 and Carm1, the levels of which are determined by both cleavage history and de novo transcription. This study shows that symmetry breaking leading to lineage specification is a continuous process that emerges as early as the two-cell stage, before morphological differences between blastomeres are detectable.

Revising the origin of thyroid C cells

Thyroid C cells (or parafollicular cells) are neuroendocrine cells found in the thyroid gland that secrete calcitonin. To date, it has been thought that these cells arise from the neural crest but here, on p. 3519, Mikael Nilsson and co-workers overturn this view. Using lineage tracing, they show that Wnt1-positive neural crest cells do not give rise to C cells in the mouse embryonic thyroid gland. Instead, they reveal, thyroid C cells are derived from Sox17-positive anterior endoderm. The researchers further show that the transcription factors Foxa1 and Foxa2, which are known to play a role in the development of other endoderm-derived populations, are co-expressed in C cell precursors, where they play non-redundant roles. Finally, the authors also show that Foxa1 and Foxa2 are expressed and appear to play distinct roles in human medullary thyroid carcinoma (MTC) cells. Together, these findings disprove the current concept of a neural crest origin of thyroid C cells and argue that MTC tumours should be reclassified as neuroendocrine tumours with an endodermal origin, a change that, from a clinical perspective, may open up new avenues in the search for MTC treatments.

Lin-28: balancing stem cell divisions

The Drosophila intestine is known to undergo adaptive growth in response to feeding, and this growth is fuelled by the symmetric self-renewing divisions of intestinal stem cells (ISCs). But what controls ISC division patterns? Here, on p. 3478, Nicholas Sokol and colleagues reveal that the RNA-binding protein Lin-28 promotes symmetric ISC divisions and hence tissue growth in the Drosophila intestine. They first show that Lin-28 is highly enriched in adult Drosophila ISCs. They further report that, although lin-28 null mutants are viable, adult mutant animals exhibit reduced numbers of ISCs. Following on from this, the researchers demonstrate that Lin-28 is required in ISCs to promote food-triggered self-renewing divisions and expansion of the ISC pool. Finally, they report that Lin-28 acts independently of its well-known target let-7 and instead interacts with mRNA encoding the insulin-like receptor (InR), suggesting that Lin-28 modulates InR levels, and thus insulin signalling, to control cell division patterns. In summary, the authors propose that Lin-28 acts as a stem cell intrinsic factor that boosts insulin signalling in ISCs and promotes their symmetric division in response to nutrients.

PLUS:

An interview with Mike Levine

Mike Levine, director of the Lewis-Sigler Institute for Integrative Genomics at Princeton University, is a developmental biologist who has dedicated his career to understanding how gene expression is regulated during development. We had a lively chat with Mike at this year’s Society for Developmental Biology meeting, where he was awarded the Edwin Grant Conklin Medal. See the Spotlight article on p. 3453

Heparan sulfate proteoglycans: a sugar code for vertebrate development?

Heparan sulfate proteoglycans (HSPGs) have long been implicated in a wide range of cell-cell signaling and cell-matrix interactions, both in vitro and in vivo in invertebrate models. Here, Poulain and Yost provide a comprehensive overview of the various roles of HSPGs in these systems and explore the concept of an instructive heparan sulfate sugar code for modulating vertebrate development. See the Review on p. 3456

Featured movie

This issue’s featured movie shows mouse development from E11.5 to E14.0, as displayed in the 4D atlas of mouse development developed by Wong and colleagues. Read their paper on this useful resource: http://bit.ly/1NeEiAg

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Department/Location: Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, UK

Salary: £24,775-£28,695

Reference: PS07303

Closing date: 12 November 2015

Fixed-term: The funds for this post are available until 30 June 2017 in the first instance.

The Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute (SCI) comprises 200 researchers spanning fundamental science through to clinical applications. Our goal is to advance disease modelling, drug discovery and regenerative medicine through understanding the genetic and biochemical mechanisms that control stem cell fate.

Applications are invited for a computational biologist to join the SCI’s bioinformatics group. We apply state-of-the-art experimental and computational methods toward understanding the biological properties and biomedical potential of stem cells.

The vacant post is at Research Assistant level and would be suitable for individuals with either a computational or biological background. The post holder will bridge the research groups within the SCI and will analyse next generation sequencing data using cutting edge software tools on internally (SCI)-produced data. He/she will work in a team of bioinformaticians dedicated to the application of modern bioinformatics techniques to stem cell research.

Candidates should be able to work in a UNIX/Linux environment. Proficiency with a scripting language (e.g. Perl/Python) and statistical data analysis tools (R, Matlab) would be a strong advantage. Additional experience with analysis of high-throughput sequencing data is desirable. The post holder will be involved in the development and interpretation of multilayer genomic, transcriptomic and epigenomic data. Necessary training in specialist computational tools will be provided; the main criterion is an enthusiasm to use bioinformatic approaches to advance stem cell research.

To apply online for this vacancy and to view further information about the role, please visit: http://www.jobs.cam.ac.uk/job/8347. This will take you to the role on the University’s Job Opportunities pages. There you will need to click on the ‘Apply online’ button and register an account with the University’s Web Recruitment System (if you have not already) and log in before completing the online application form.

Please upload your Curriculum Vitae (CV) and a covering letter in the Upload section of the online application to supplement your application. If you upload any additional documents which have not been requested, we will not be able to consider these as part of your application.

The closing date for all applications is the Thursday 12 November 2015.

Informal enquiries about the post are also welcome via email on jobs@stemcells.cam.ac.uk.

Interviews will be held week commencing 23 November 2015. If you have not been invited for interview by 23 November 2015, you have not been successful on this occasion.

Please quote reference PS07303 on your application and in any correspondence about this vacancy.

The University values diversity and is committed to equality of opportunity.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

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Evolution and development of shark skin teeth inspired surface design for global CO2 reduction

Dr Gareth Fraser, APS, University of Sheffield;
Co-supervisors: Dr Mark Johnson, Department: School of Engineering, Centre for Engineering Dynamics, University of Liverpool;
Dr Zerina Johanson, Natural History Museum, London, Department of Earth Sciences

A Ph.D studentship is available for an interdisciplinary project focused on evolutionary developmental biology of shark skin teeth and engineering shark-inspired surface geometries for reduced drag leading to lower CO2 emissions across several industries. This is an ideal opportunity for an ambitious candidate to work at the interface of evo-devo and engineering. This project aims to explore novel methods to understand the evolution and development of shark tooth patterning and how these data can be modelled in silico for more energy efficient surface design that can be 3D-printed for functional models of drag reduction. This project would suit a candidate interested in skin tooth development in sharks and the diversity of these structures in pattern and morphology across species to understand the most efficient patterns and geometries in nature, and then how nature can help us develop solutions to environmental issues in the engineering industry.

More information about this Ph.D opportunity can be found here: https://acce.shef.ac.uk/shark-skin-inspired-surface-design-for-co2-reduction/

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Here is October’s round-up of some of the interesting content that we spotted around the internet!

News & Research

– Developmental Biologist Eric Davidson, who was based at CalTech, has sadly passed away. You can learn more about Eric and his career in this Q&A published in Current Biology a few years ago.

– Interesting piece in Nature News considers how biohackers (amateur biologists) are using CRISPR.

– We found this excellent resource detailing how to display your figures in a colourblind-friendly manner.

– Do papers with shorter titles really get cited more?

– ‘When did you decide to?’- how most people don’t have clear career paths planned. By Athene Donald.

– The forgotten benefits of drawing in science- in Scientific American.

– Masayo Takahashi is the winner of the inaugural Ogawa-Yamanaka Stem Cell Prize, awarded by the Gladstone Institutes. Also don’t miss the chance to vote for the 2015 Stem Cell Person of the Year in Paul Knoepfler’s blog.

– How to unboil an egg and how to make a chicken walk like a dinosaur are just some of the winners of this year’s Ig Nobel prizes.

– How scientists fool themselves and how they can stop- preventing bias in science, in Nature.

– Fish out of water- the challenges of being an academic outside your country, in THE.

– The MRC shared their 12 top tips for writing a grant application.

– And we rediscovered an old piece by Jeff Schatz on how (not) to give a seminar.

Weird & Wonderful

– We spotted these cool notebooks, hand-embroidered with vintage science illustrations.

– Need to explain the difference between correlation and causation? These helpful (and hilarious!) graphs will come handy.

– ‘I need 10,000 marks’– was all you needed to say to get your research funded back in 1921.

– And this is how you explain what it is like to be a developmental biologist to a 4 year old:

Some Friday inspiration. pic.twitter.com/KMGpKm42h5

— Barry Thompson (@ThompsonLab) August 21, 2015

Beautiful & Interesting images:

– Tracking C. elegans development- the drawings of Sir John Sulston.

– We spotted this colourful embryology notebook from a 1939 course at MBL.

– And this is just one of our favourite creations from this year’s Agar Art contest, run by the American Society of Microbiology:  

Vincent van Gogh’s “The Starry Night” #agarart2015 http://t.co/E5bpvDqVnE pic.twitter.com/UU7FArLh5l — Microbiology (@MicrobiologyRR) September 2, 2015

Videos worth watching:

– The PHD Movie 2 is now screening! Check out the dates and venues.

– And this fun movie is a great way to explain concepts of evolution… especially for the Pokemon fans among you:

Keep up with this and other content, including all Node posts and deadlines of coming meetings and jobs, by following the Node on Twitter

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In multicellular animals and plants, the single-celled zygote develops into the embryo. In the model plant Arabidopsis thaliana, the zygote divides asymmetrically to form a small cytoplasmic apical cell, which is the precursor of the proembryo, and a large vacuolated basal cell, which develops into the extra-embryonic suspensor (Figure 1). Communication between the intra-embryo (proembryo and suspensor) and the inter-embryo (embryo and surrounding tissues) is required for proliferation, pattern formation, and differentiation during embryogenesis^1-3. Moreover, it has long been known that in several plant species, including Arabidopsis, disruption of the original embryonic tissue induces formation of newly embryonic cells derived from the extra-embryonic tissue^4-6. However, the process by which an embryonic cell is initiated from the extra-embryonic tissue remains unclear. Angiosperm embryogenesis in vivo occurs within multiple layers of maternal tissues within the flower; therefore it is difficult to observe and analyze the intercellular communications in living material in real time. The development of a live-cell imaging system has been long-awaited to reveal how cell fate is specified by intercellular communication during early embryogenesis. Recently, we have developed a live-embryo imaging system to visualize cell division and cell-fate specification in Arabidopsis thaliana. We incorporated two advanced technologies—micro-engineering and optical manipulation—into this system.

First, we developed an in vitro ovule culture system so that time-lapse imaging could be performed. An in vitro culture system was necessary for real-time observation because embryogenesis could not be observed in vivo on account of the deep tissues. However, we could not observe any cell division in the isolated early embryo⁷. Therefore, we cultured the embryo within the maternal tissue—the ovules—in vitro. We used liquid medium to prevent the ovules drying up during long-term culture and placed the ovules close to the cover glass. However, stable observation of the ovules in the liquid medium was difficult because of their round shape, so we fabricated PDMS [poly(dimethylsiloxane)] microdevices to adjust the orientation and fix the position of the ovules using micro-engineering techniques.

PDMS has several advantages in the field of developmental biology, such as a high level of biocompatibility, including efficient gas exchangeability and a suitable transparency for observation. PDMS-based microfluidic devices have also been used for animal cell cultures⁸. Recently, plant researchers have also started to use PDMS-based microdevices for analyzing the growth of root tips, pollen tubes, and seedlings as a lab-on-a-chip⁹. Initially, we fabricated a PDMS microcage array to fix the ovules in the liquid medium¹⁰. To increase the trapping efficiency of the ovules, we modified the PDMS microcage array to a micropillar array¹¹ (Figure 2). Micropillar arrays have a weaker effect on ovule growth because of the physiological flexibility of PDMS micropillars. Thus, we were able to conduct time-lapse imaging of cell division—from the zygote to the heart-stage embryo—for 3 days within the ovules in Arabidopsis embryogenesis.

Another advanced technique is optical manipulation. To elucidate the mechanisms of cell–cell communications within the tissues, it is important to carry out a spatio-temporal analysis to determine when, where, and which cells are communicating. Optical manipulation is a powerful tool for such real-time analysis. Because lasers have high optical intensities at the focal point, laser ablation has long been used to disrupt cells. In plants, UV lasers have been used for laser ablation^12,13. However, there are limitations to how UV lasers can be used. Short-wavelength lasers, such as UV lasers, are susceptible to refraction, absorption, and scattering from the tissues. Therefore, it is difficult to ablate the cell at the level of a single cell within deep tissues.

Recently, near-infrared pulse lasers have been gradually used to overcome the limitation of UV lasers. Near-infrared pulse lasers are tolerant to scattering within the tissues because of their longer wavelength. In addition, femto-second pulse lasers can induce nonlinear optical effects, such as plasma formation, at a sub-femto-liter volume. Thus it can induce damage even within a cell¹⁴. Hasegawa et al. performed the disruption of actin filaments within a tobacco-cultured cell using a femto-second pulse laser in real time¹⁵.

We performed laser disruption to our live-embryo imaging system using a femto-second pulse laser¹¹. When an apical cell (embryonic cell) was disrupted by laser irradiation, the cell fate of the remnant basal cell (extra-embryonic cell) was converted, through changes in identity gene expression, into an embryonic cell (Figure 3). In terms of the disruption of basal cells, we found that apical cells were not converted into basal cells. Thus, we succeeded in performing real-time observation of cell-fate conversion for the compensation of an embryonic cell. We propose that the fate and behavior of each individual cell in Arabidopsis embryos is determined via intercellular communication with neighboring cells, and that such flexibility contributes to the robustness of plant embryogenesis.

Our imaging system enables direct visualization of the dynamics of cell-fate specification during embryogenesis using micro-engineering techniques. In plants, cell fates are specified via positional information during development. Femto-second laser irradiation, as a form of optical manipulation, enables a spatio-temporal induction of cell-fate conversion that is impossible with genetic ablation. Thus, these techniques will enable novel insights into the molecular mechanisms of cell-fate specification via intercellular communication in plant development. Moreover, these techniques are highly suited to research into developmental biology as well as to plant research, so will be of interest to broad developmental biologists in addition to their applicability to live-cell analysis.

1         Kawashima, T., & Goldberg, R. (2010). The suspensor: not just suspending the embryo Trends in Plant Science, 15 (1), 23-30 DOI: 10.1016/j.tplants.2009.11.002

2          Javelle, M., Vernoud, V., Rogowsky, P., & Ingram, G. (2011). Epidermis: the formation and functions of a fundamental plant tissue New Phytologist, 189 (1), 17-39 DOI: 10.1111/j.1469-8137.2010.03514.x

3          Lafon-Placette, C., & Köhler, C. (2014). Embryo and endosperm, partners in seed development Current Opinion in Plant Biology, 17, 64-69 DOI: 10.1016/j.pbi.2013.11.008

4          Haccius, B. (1955). Experimentally Induced Twinning in Plants. Nature 176, 355-356, doi:Doi 10.1038/176355a0

5          Yeung, E., & Meinke, D. W. (1993). Embryogenesis in Angiosperms: Development of the Suspensor Plant Cell, 5 (10), 1371-1381 DOI: 10.1105/tpc.5.10.1371

6          Schwartz, B. W., Yeung, E. C. & Meinke, D. W. (1994). Disruption of Morphogenesis and Transformation of the Suspensor in Abnormal Suspensor Mutants of Arabidopsis. Development 120, 3235-3245 DOI:

7          Kurihara, D., Hamamura, Y., & Higashiyama, T. (2013). Live-cell analysis of plant reproduction: Live-cell imaging, optical manipulation, and advanced microscopy technologies Development, Growth & Differentiation, 55 (4), 462-473 DOI: 10.1111/dgd.12040

8          Bhatia, S., & Ingber, D. (2014). Microfluidic organs-on-chips Nature Biotechnology, 32 (8), 760-772 DOI: 10.1038/nbt.2989

9          Sanati Nezhad, A. (2014). Microfluidic platforms for plant cells studies Lab on a Chip, 14 (17), 3262-3274 DOI: 10.1039/C4LC00495G

10        Park, J., Kurihara, D., Higashiyama, T., & Arata, H. (2014). Fabrication of microcage arrays to fix plant ovules for long-term live imaging and observation Sensors and Actuators B: Chemical, 191, 178-185 DOI: 10.1016/j.snb.2013.09.060

11        Gooh, K., Ueda, M., Aruga, K., Park, J., Arata, H., Higashiyama, T., & Kurihara, D. (2015). Live-Cell Imaging and Optical Manipulation of Arabidopsis Early Embryogenesis Developmental Cell, 34 (2), 242-251 DOI: 10.1016/j.devcel.2015.06.008

12        van den Berg C, Willemsen V, Hendriks G, Weisbeek P, & Scheres B (1997). Short-range control of cell differentiation in the Arabidopsis root meristem. Nature, 390 (6657), 287-289 PMID: 9384380

13       Higashiyama, T., Yabe, S., Sasaki, N., Nishimura, Y., Kuroiwa, H., & Kuroiwa, T. (2001). Pollen Tube Attraction by the Synergid Cell Science, 293 (5534), 1480-1483 DOI: 10.1126/science.1062429

14       Tirlapur, U., & König, K. (2002). Targeted transfection by femtosecond laser Nature, 418 (6895), 290-291 DOI: 10.1038/418290a

15        Hasegawa, J., Higaki, T., Hamamura, Y., Kurihara, D., Kutsuna, N., Higashiyama, T., Hasezawa, S. & Matsunaga, S. (2014). Vacuole subdivision in plant cell growth by the genotoxic stress inducing DNA double strand breaks. Cytologia 79, 467-474, doi:10.1508/cytologia.79.467

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This Sticky Wicket article first featured in Journal of Cell Science. You can read the Mole’s visit to the first 5 circles of Grant Hell here. Read other articles and cartoons of Mole & Friends here.

Mole was revising his rejected grant and moaning about how unfair it all is, when the shade of Francis Bacon, the Father of the Scientific Method, appeared to take him on a tour of Grant Hell. Sir Francis (‘Frank’) looks like Dumbledore but talks like a wanna-be hipster but, hey, maybe Mole is just dreaming all this. Anyway, they went to Grant Hell. There, they met lots of wretched souls who were not successful in revising their grants, and had lots of reasons why not.

Oh, one more thing. For some reason, the story is told in triplets that don’t rhyme. Probably they did in some other language, but it would have been too much trouble to translate it and make it rhyme. Mole may be getting lazy. Or maybe he’s up to something? No, most likely he’s just lazy. We join our travelers, having passed the Fifth Circle, and have continued up to the Fourth.

“Here is the Fourth Circle,” said Frank. This was Greed.

“But hey,” I said, “I thought greed is good. That’s what they tell us,

It makes the market work.” Frank shook his head.

“Wait,” I said, “Are you saying that these poor people are here

Because they wanted to do too much? They wanted too many grants?

I mean, what’s wrong with a little ambition if the science is good?

“Listen,” I went on, “I’m getting a little tired of hearing that somebody, who

I think is a really terrific scientist, has ‘too many grants.’ I mean, if they are

Getting the best work done, maybe they deserve the grants. You know?”

“And now,” I think I was on a roll. “Now you tell me that they are here,

In Grant Hell, because they work too hard.”¹ “Easy, Big Guy,²” said Frank,

And I looked to see if he was talking to me. He was. Nobody calls me ‘Big Guy.’

He went on. “You’ve got it all wrong. They aren’t here because they wanted

Too many grants. They are here because they confused grant funding and power.

Their greed is not to do more great science but to amass influence.”

“Oh,” I said. “Then they get what they deserve.” Because being ‘powerful’

As a research scientist is a bit like being the King or Queen of Cheese.³

It isn’t worth very much and can smell pretty terrible. Frank cracked up at that one.

We had moved to the Third Circle, where the wretched never stopped writing,

Except to eat the paper they were generating. Or electrons, but I couldn’t see that.

Then they would write some more. “Here is Gluttony,” whispered Frank.

I stopped one poor soul who was eating a page as it came out of a printer.

“Why are you doing this?” I asked. “Oh,” he moaned. “You know how it is,

I don’t get my grants funded, so I write more and more and more.

“I was putting in a grant every cycle, but that didn’t work, so I went to two,

Then three. I don’t have anything new to say, and I spend all my time

Regurgitating my ideas and sending them in. Eventually I’ll get one.” He belched.

“But wait,” I cried, “Maybe you need to stop and actually think about what

You are writing! Maybe if you took some time out, you’d frame the work

In a way that reviewers will see why it is important?” He wolfed down a page.

“No, this is how I do it,” he sputtered between mouthsful. “This is how I roll.”

“How’s that working out for you?” I asked, but he wasn’t interested.⁴

“Let’s go up,” said Frank. “Not much more to see here.”

We found the Second Circle. Souls were flying in the winds that blew around us.

“This is Lust,” said Frank, watching them flit around us. “Their only crime, I think,

Is to want their grant too badly. They don’t want to change it, because they love it.”

I could understand. Maybe this was my own circle. I really, really want my grant.

I lust for it. The work is lovely, and elegant, and important. But it wasn’t funded.

I could feel myself starting to float off the ground and my clothes began to flap.

“Whoa, there, Compadre,⁵” said Frank, grabbing my leg and bringing me to earth.

“Get a grip. I mean, its just a proposal for what you want to do. There’s nothing

of value in a grant, except as a way to get the support for the work, right?”

I wasn’t so sure. I mean, when I write a grant, I think about the project,

Really think about it, often for months. The act of writing helps me to formulate,

Consolidate my thoughts. It’s a plan for the next few years of research.

But yes, he was also right. The act of writing a grant, really, is just an approach

To supporting the work that has been formulated. Yes, thinking about it is good,

But actually doing the work is what this is all about. I needed to think.

And found that we had entered the First Circle. Limbo. Nothing to do but wait.

And while we all waited to hear the results of our submission, we were happy.

Because until we get the bad news, we can imagine that we’ll get it.

We emerged in the light of Hope. And there, before us, was a mountain.

“We’ll climb that in a while,⁶” said Frank. “But first, I know a good place

Near here to get some lunch. You down for that?” Me, I didn’t know down from up.

Footnotes

↵1 Mole is correct here, and despite FB’s words to the contrary, many experienced investigators have their grants fail because of a perception that “they have too much money.” Indeed, funding institutions sometimes place limits on total amounts a program may have, and in those that do not, the reviewers may take this position themselves. But Mole feels that this is inappropriate; some investigators are simply more productive than others and, given the opportunity, more support can result in substantially more impactful research from such investigators. Of course, the opposite is also true – there are investigators who will not be productive, regardless of how much support they have.

↵2 Grande Salame

↵3 (il re o la regina di formaggio) It is possible that Mole is referring to either King Camembert (1411–1489) or, perhaps, Queen Gouda (1536–1590). Or he may be referring to his friend Weasel who is, indeed, very fond of cheese.

↵4 This approach, of flooding granting institutions with applications in hopes that one may “stick” is becoming much too common. Mole doubts that it is a viable strategy, unless such multiple applications can be done with the same care that goes into only one. As this is rarely the case, the strategy might, at least, be reconsidered. Given that the result is an avalanche of hastily prepared applications converging at any one competition, an exceptionally well-crafted (and well-reasoned) application might stand out and be favored. It’s just a thought.

↵5 (Fermati, il mio Ferrari)

↵6 The mountain, Grant Purgatory, eventually leads to Grant Paradise, which lasts only until the period of the grant runs out, and a renewal applied for. Mole points out that it may be interesting to note that, whenever a grant is rejected and we find ourselves in Grant Hell, we blame the process (“they killed me”). When it happens that we emerge into the light of funded Grant Paradise, though, we did it all by ourselves (“yes, I got the grant”).

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Xenbase (www.xenbase.org) is the Xenopus bioinformatics and genomics resource. Xenopus is a major model for fundamental cell and developmental biology and a model for human disease. Xenbase is a totally free, and globally accessible database, used by Xenopus researchers worldwide, and is funded by the National Institute of Child Health and Human Development. Xenbase has two performance sites: the curation team is based in Cincinnati, OH (PI: Dr. Aaron Zorn) and the developer/database management team is based at the University of Calgary in Canada (PI: Dr. Peter Vize).

Xenbase is seeking to fill 2 full time Curation positions to join the curation team at the Division of Developmental Biology, Cincinnati Children’s Hospital, Cincinnati, OH, USA. Curation positions offer a challenging job away from the wet-lab and research bench, where interpreting, annotating and displaying complex data is our main task. Curators also develop strategies to improve data curation; work to improve data display/querying on the website; interact with our user community at research conferences; develop programming skills; and contribute to Xenbase publications.

Job Description:

• Curation and annotation of published Xenopus scientific literature, focusing on gene expression and the extraction of other research data: genes, transgenics, antibodies, morpholinos, phenotypes, genetic interactions, gene product functions and models of human disease.
• Import and annotate data from large-scale screens (e.g., loss-of-function morpholino screens, gain-of-function mRNA screens).
• Help develop new features: curation and processing of public and directly submitted RNA-seq and ChIP-seq NGS data from Xenopus experiments, curation of mutant phenotypes and transgenics; expanding our an anatomy atlas; implementing GO annotations.
• Co-author reports and publications, and give presentations at national and international meetings and workshops.

Qualifications:

• MSc or PhD degree in bioinformatics and/or developmental biology, genomics, genetics, molecular biology, zoology, anatomy or related field.
• Demonstrated ability to produce scientific papers, reports and presentations
• Demonstrated ability to work in a team as well as independently, efficiently (i.e both quickly and accurately) and be self-motivated
• Strong interpersonal and communication skills, including excellent written and spoken English

Preference will be given to applicants with:

• Experience with a bioinformatics, genomics or model organism database
• Experience in data annotation/biocuration, knowledge of relational databases, and familiarity with ontologies.
• Experience in a Xenopus or other vertebrate (mouse, zebrafish or chick) developmental biology lab.
• Experience in analyzing genomics data, using GRN software, genome browsers and common bioinformatics tools.

How to Apply:

Please submit your application, to: aaron.zorn[at]cchmc.org with the following information:

• A cover letter , including a statement of interest/purpose
• CV/Resume.
• Copy of your degree(s).
• List 3 references/referees whom we may contact (please include their postal address, email and phone number).

Salary and Start Date:

Salary will be commensurate with qualifications and experience. Start date is negotiable, but expected to be in early 2016.

The successful applicants will be employees of Cincinnati Children’s Hospital and will undergo background checks, orientation and a 3-month probationary period. Employees are required to receive an annual flu vaccination.

More information about working at Cincinnati Children’s Hospital and living in Cincinnati can be found here: http://www.cincinnatichildrens.org/careers/working/default/

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PhD opportunities available here:

http://biodtp.norwichresearchpark.ac.uk/projects

Use the search functions for particular topics or partner institutions, which include the JIC, TGAC, IFR, TSL and the UEA.

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Using chick embryos we recently identified BMP/Smad and Wnt/GSK3b signals as extrinsic cues that control the migration of prospective cardiac cells. We showed that BMP and Wnt pathways converge on a common effector: the transcription factor Smad1 (Song, McColl et al., PNAS 2014). We will use systematic approaches to determine the targets of BMP/Smad1 and Wnt/GSK3b signalling in early mesoderm cells. Identified candidate genes will be assessed for their function in controlling cell migration and fate choice.

More information can be found here http://www.jobs.ac.uk/job/AMD289/senior-research-associate/

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New call for applications for DTP studentships in the Department of Biological and Medical Sciences at Oxford Brookes University:

http://bms.brookes.ac.uk/research/studentships

The application deadline is 12 noon on November 20th.

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