Our latest monthly trawl for developmental biology (and other cool) preprints. See June’s post for background, and let us know if we missed anything

This month features quite a bit of cell biology, both in early embryos and in a dish, with work on microtubules from the labs of Andreas Prokop, Tim Mitchison and Manuel Thery.  We also found investigations into zebrafish cell migration and gastrulation, lots of new C. elegans work, a new view on superenhancers, some genomed Swedes, and some cats.

As in the last months, the preprints predominantly came from bioRxiv, but we also found some in PeerJ and arXiv.  If we missed anything out, let us know. Happy preprinting!

Developmental biology

Collective epithelial migration drives timely morphogenesis of the retinal neuroepithelium. Jaydeep Sidhaye, Niklas Ifflaender, Caren Norden

Kinematic analysis of cell lineage reveals coherent and robust mechanical deformation patterns in zebrafish gastrulation. David Pastor-Escuredo, Benoit Lombardot, Thierry Savy, Adeline Boyreau,Jose M. Goicolea, Andres Santos, Paul Bourgine, Juan C. del Alamo, Nadine Peyrieras, Maria J. Ledesma-Carbayo.

A microRNA family exerts maternal control on sex determination in C. elegans. Katherine McJunkin, Victor Ambros

Casein Kinase II is Required for Proper Cell Division and Acts as a Negative Regulator of Centrosome Duplication in C. elegans Embryos. Jeffrey C Medley, Megan M Kabara, Michael D Stubenvoll, Lauren E DeMeyer, Mi Hye Song

Sexually dimorphic differentiation of a C. elegans hub neuron is cell-autonomously controlled by a conserved transcription factor. Esther Serrano Saiz, Meital Oren-Suissa, Emily Ann Bayer, Oliver Hobert

The nematode homologue of Mediator complex subunit 28, F28F8.5, is a critical regulator of C. elegans  development.  Markéta Kostrouchová, David Kostrouch, Ahmed A Chughtai, Filip Kaššák, Jan P. Novotný, Veronika Kostrouchová, Aleš Benda, Michael W. Krause, Vladimír Saudek, Marta Kostrouchová, Zdenek Kostrouch

Transcriptomic Description of an Endogenous Female State in C. elegans. David Angeles-Albores, Daniel H. W. Leighton, Tiffany Tsou, Tiffany H Khaw, Igor Antoshechkin, Paul Sternberg

Mcmdc2, a minichromosome maintenance (MCM) paralog, is required for repair of meiotic DNA breaks and homolog pairing in mouse meiosis. Adrian J McNairn, Vera D Rinaldi, John C Schimenti

Dynamic changes in Sox2 spatio-temporal expression direct the second cell fate decision through Fgf4/Fgfr2 signaling in preimplantation mouse embryos. Tapan Kumar Mistri, Wibowo Arindrarto, Wei Ping Ng, Choayang Wang, Hiong Lim Leng, Lili Sun, Ian Chambers, Thorsten Wohland, Paul Robson

Mice deficient of Myc super-enhancer region reveal a differential control mechanism between normal and pathological growth. Kashyap Dave, Inderpreet Sur, Jian Yan, Jilin Zhang, Eevi Kaasinen, Fan Zhong, Leander Blaas, Xiaoze Li, Robert Mansson, Jussi Taipale

Neuropilin 1 sequestration by neuropathogenic mutant glycyl-tRNA synthetase is permissive to vascular development and homeostasis. James Nicholas Sleigh, Adriana Gomez-Martin, Giampietro Schiavo

A dual-strategy expression screen for candidate connectivity labels in the developing thalamus. Olivia Bibollet-Bahena, Tatsuya Okafuji, Karsten Hokamp, Kevin J. Mitchell

Oligodendrocytes in the mouse optic nerve originate in the preoptic area. Katsuhiko Ono, Kengo Yoshii, Hiroyuki Tominaga, Hitoshi Gotoh, Tadashi Nomura, Hirohide Takebayashi, Kazuhiro Ikenaka

High temporal resolution of gene expression dynamics in developing mouse embryonic stem cells. Brian S Gloss, Bethany Signal, Seth W Cheetham, Franziska Gruhl, Dominik Kaczorowski, Andrew C Perkins, Marcel E Dinger

Periodic actin structures in neuronal axons are required to maintain microtubules. Yue Qu, Ines Hahn, Stephen Webb, Simon P. Pearce, Andreas Prokop

A Novel function for Cactus/IκB inhibitor to promote Toll signals in the Drosophila embryo. Maira A Cardoso, Marcio R Fontenele, Bomyi Lim, Paulo M Bisch, Stanislav Shvartsman, Helena M Araujo

A shielded irradiation assay to investigate mechanisms of in vivo stem cell migration in planarians. Prasad Abnave, Ellen Aboukhatwa, Nobuyoshi Kosaka, James Thompson, Mark Hill, Aziz Aboobaker

Computational study of the impacts of mechanical and physical cell properties on mitotic cell rounding in developing epithelia. Ali Nematbakhsh, Wenzhao Sun, Pavel A Brodskiy, Aboutaleb Amiri, Cody Narciso, Zhiliang Xu, Jeremiah J Zartman, Mark S Alber

Exploratory bioinformatics analysis reveals importance of “junk” DNA in early embryo development. Steven Xijin Ge

Frequency of mosaicism points towards mutation-prone early cleavage cell divisions. Chad Harland, Carole Charlier, Latifa Karim, Nadine Cambisano, Manon Deckers, Erik Mullaart, Wouter Coppieters, Michel Georges

Single Cell Expression Data Reveal Human Genes that Escape X-Chromosome Inactivation. Kerem Wainer-Katsir, Michal Linial

Morphological plant modeling: Unleashing geometric and topologic potential within the plant sciences. Alexander Bucksch, Acheampong Atta-Boateng, Akomian Fortune Azihou, Mathilde Balduzzi, Dorjsuren Battogtokh, Aly Baumgartner, Brad Binder, Siobhan Braybrook, Cynthia Chang, Viktoriya Coneva, Thomas DeWitt, Alexander Fletcher, Malia Gehan, Diego Hernan Diaz Martinez, Lilan Hong, Anjali Iyer-Pascuzzi, Laura Klein, Samuel Leiboff, Mao Li, Jonathan Lynch, Alexis Maizel, Julin Maloof, RJ Cody Markelz, Ciera Martinez, Laura Miller, Washington Mio, Wojtek Palubicki, Hendrik Poorter, Christophe Pradal, Charles Price, Eetu Puttonen, John Reese, Ruben Rellan-Alvarez, Edgar Spalding, Erin Sparks, Chris Topp, Joseph Williams, Daniel Chitwood

Multi-Compartmental Biomaterial Scaffolds for Patterning Neural Tissue Organoids in Models of Neurodevelopment and Tissue Regeneration. Richard J. McMurtrey

Cell Biology

Physical basis of large microtubule aster growth. Keisuke Ishihara, Kirill S Korolev, Timothy J Mitchison

CENP-F couples cargo to growing and shortening microtubule ends. Gil Kanfer, Martin Peterka, Vladimir K. Arzhanik, Alexei L. Drobyshev, Fazly I. Ataullakhanov, Vladimir A. Volkov, Benoît Kornmann

Microtubule stabilization drives centrosome migration to initiate primary ciliogenesis. Amandine Pitaval, Fabrice Senger, Gaelle Letort, Xavier Gidrol, James Sillibourne, Manuel Thery

The duration of mitosis and daughter cell size are modulated by nutrients in budding yeast. Ricardo Mendes Leitao, Annie Pham, Douglas Kellogg

Crossover in the dynamics of cell wall growth controls Caulobacter division times. Shiladitya Banerjee, Klevin Lo, Alan Selewa, Thomas Kuntz, Matthew K Daddysman, Aaron R Dinner, Norbert F Scherer

Probing the effect of uniaxial compression on cell migration. Nishit Srivastava, Robert R Kay, Alexandre J Kabla

Disease models

Zika infection of neural progenitor cells perturbs transcription in neurodevelopmental pathways. Lynn Yi, Harold Pimentel, Lior Pachter

Single Cell Phenotyping Reveals Heterogeneity among Haematopoietic Stem Cells Following Infection. Adam L MacLean, Maia A Smith, Juliane Liepe, Aaron Sim, Reema Khorshed, Nico Scherf, Axel Krinner, Ingo Roeder, Cristina Lo Celso, Michael PH Stumpf

A Saposin deficiency model in Drosophila: lysosomal storage, progressive neurodegeneration, sensory physiological decline and defective calcium homeostasis. Samantha J Hindle, Sarita Hebbar, Dominik Schwudke, Christopher J Elliott, Sean T Sweeney

Distal axotomy enhances retrograde presynaptic excitability onto injured pyramidal neurons via trans-synaptic signaling. Tharkika Nagendran, Rylan Larsen, Rebecca Bigler, Shawn Frost, Benjamin Philpot, Randolph J. Nudo, Anne Marion Taylor

Resources & Techniques

Mocap: Large-scale inference of transcription factor binding sites from chromatin accessibility. Xi Chen, Bowen Yu, Nicholas Carriero, Claudio Silva, Richard Bonneau

Pooled CRISPR screening with single-cell transcriptome read-out. Paul Datlinger, Christian Schmidl, Andre F Rendeiro, Peter Traxler, Johanna Klughammer, Linda Schuster, Christoph Bock

Transcriptional landscape of cell lines and their tissues of origin. Camila Miranda Lopes-Ramos, Joseph N Paulson, Cho-Yi Chen, Marieke L Kuijjer, Maud Fagny, John Platig, Abhijeet R Sonawane, Dawn L DeMeo, John Quackenbush, Kimberly Glass

Whole genome resequencing of a laboratory-adapted Drosophila melanogaster population sample. William P. Gilks, Tanya M Pennell, Ilona Flis, Matthew T Webster, Edward H. Morrow

SweGen: A whole-genome map of genetic variability in a cross-section of the Swedish population. Adam Ameur, Johan Dahlberg, Pall Olason, Francesco Vezzi, Robert Karlsson, Par Lundin, Huiwen Che, Jessada Thutkawkorapin, Andreas Kusalananda Kahari, Mats Dahlberg, Johan Viklund, Jonas Hagberg, Niclas Jareborg, Inger Jonasson, Asa Johansson, Sverker Lundin, Daniel Nilsson, Bjorn Nystedt, Patrik Magnusson, Ulf Gyllensten

Semi-automated genome annotation using epigenomic data and Segway. Eric G. Roberts, Mickaël Mendez, Coby Viner, Mehran Karimzadeh, Rachel C. W. Chan,Rachel Ancar, Davide Chicco, Jay R. Hesselberth,Anshul Kundaje, Michael M. Hoffman

SCORPIUS improves trajectory inference and identifies novel modules in dendritic cell development. Robrecht Cannoodt, Wouter Saelens, Dorine Sichien, Simon Tavernier, Sophie Janssens, Martin Guilliams, Bart N Lambrecht, Katleen De Preter, Yvan Saeys.

Development of a modular automated system for maintenance and differentiation of adherent human pluripotent stem cells. Duncan E Crombie, Maciej Daniszewski, Helena H Liang, Tejal Kulkarni, Fan Li, Grace E Lidgerwood, Alison Conquest, Damian Hernandez, Sandy S Hung, Katherine P Gill, Elisabeth De Smit, Lisa S Kearns, Linda Clarke, Valentin M Sluch, Xitiz Chamling, Donald J Zack, Raymond CB Wong, Alex Hewitt, Alice Pebay

Evolution etc

Recombination Suppression is Unlikely to Contribute to Speciation in Sympatric Heliconius Butterflies. John W. Davey, Sarah L. Barker, Pasi M. Rastas, Ana Pinharanda, Simon H. Martin, Richard Durbin, Richard M. Merrill, Chris D. Jiggins

Evolutionary determinants of morphological polymorphism in colonial animals. Carl Simpson, Jeremy B.C. Jackson, Amalia Herrera-Cubilla

Cytoplasmic-nuclear incompatibility between wild-isolates of Caenorhabditis nouraguensis. Piero Lamelza, Michael Ailion

Transition from environmental to partial genetic sex determination in Daphnia through the evolution of a female-determining incipient W-chromosome. (Revision) Celine M. O. Reisser, Dominique Fasel, Evelin Hurlimann, Marinela Dukic, Cathy Haag-Liautard, Virginie Thuillier, Yan Galimov, Christoph R Haag

The genome of the crustacean Parhyale hawaiensis: a model for animal development, regeneration, immunity and lignocellulose digestion. (Revision) Damian Kao, Alvina G Lai, Evangelia Stamataki, Silvana Rosic, Nikolaos Konstantinides, Erin Jarvis, Alessia Di Donfrancesco, Natalia Pouchkina-Stantcheva, Marie Semon, Marco Grillo, Heather Bruce, Suyash Kumar, Igor Siwanowicz, Andy Le, Andrew Lemire, Michael Eisen, Cassandra Extavour, William Browne, Carsten Wolff, Michalis Averof, Nipam H Patel, Peter Sarkies, Anastasios Pavlopoulos, Aziz Aboobaker

Spatiotemporal patterns of desiccation tolerance in natural populations of Drosophila melanogaster. Subhash Rajpurohit, Eran Gefen, Alan Bergland, Dmitri Petrov, Allen Gibbs, Paul Schmidt

Evolving Notch polyQ tracts reveal possible solenoid interference elements. Albert J Erives

Pre-metazoan origin of animal miRNAs. (Revision) Jon Brate, Ralf Stefan Neumann,  Bastian Fromm, Arthur Alexander Blorstad Haraldsen, Paul Grini, Kamran Shalchian-Tabrizi

Challenges and solutions for transcriptome assembly in non-model organisms with an application to hybrid specimens. Arnaud Ungaro, Nicolas Pech, Jean-Francois Martin, Scott RJ McCairns, Remi Chappaz, Andre Gilles

Why not…

Of cats and men: the paleogenetic history of the dispersal of cats in the ancient world. Claudio Ottoni, Wim van Neer, Bea De Cupere, Julien Daligault, Silvia Guimaraes, Joris Peters, Nikolai Spassov, Mary E. Pendergast, Nicole Boivin, Arturo Morales-Muniz, Adrian Balasescu, Cornelia Becker, Norbert Benecke, Adina Boronenant, Hijlke Buitenhuis, Jwana Chahoud, Alison Crowther, Laura Llorente, Nina Manaseryan, Herve Monchot, Vedat Onar, Marta Osypinska, Olivier Putelat, Jacqueline Studer, Ursula Wierer, Ronny Decorte, Thierry Grange, Eva-Maria Geigl

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A fully funded postdoctoral position is available in the Laboratory of Regulatory Evolution (Tschopp group) at the Zoological Institute, University of Basel, Switzerland.

Topic of research
The lab’s research interests focus on how developmental processes can get modified, to give rise to morphological diversification on an evolutionary time-scale. As a model system, we are studying the development of the vertebrate skeleton with its associated neuromuscular system.
Vertebrate autopods (hands and feet) display the highest degree of morphological diversification in the appendicular skeleton, reflecting e.g. distinct modes of locomotion. While digit loss in the autopod has occurred in multiple vertebrate lineages, there seems to be a strong constraint to maintain the maximum number of digits at five, even though extra digits might prove beneficial in certain species.
The present project will investigate the potential for developmental plasticity in the limb neuromuscular system in response to changes in dactyly, i.e. altering digit numbers in vertebrate hands and feet. Specific questions we will address include: How are muscle patterning and motorneuron axonal pathfinding coping with changes in digit numbers in vertebrate hands and feet? How is motorneuron pool complexity in the spinal cord affected by additional digit targets in the periphery?
We will use a range of methods, including experimental embryology in chicken, genetic mouse models, axonal backfilling, NextGeneration-Sequencing and functional experiments using gene knock-down and overexpression.
For more information please visit http://evolution.unibas.ch/tschopp/research/

Your profile
The successful candidate will have a PhD in developmental biology and/or neurobiology, and will have skills in embryology, molecular biology and NextGeneration-Sequencing. Experience in axonal backfilling techniques will be a big plus. A basic understanding of Unix and the R language for statistical computing would be beneficial. You are interested in learning and using new technology to address long-standing questions in developmental and evolutionary biology.

We offer
– Highly interactive and interdisciplinary research environment
– Attractive employment conditions, very competitive salary by international standards, full funding available for 2 years
– The project builds on a solid foundation of confirmed preliminary data

Application / Contact
Please send your application with a brief statement of motivation, a current CV and contacts for references to patrick.tschopp@unibas.ch
Evaluation will begin on Dec. 1st 2016 and suitable candidates will be contacted shortly after. Earliest starting date is 1 January 2017.

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Here are the highlights from the current issue of Development:

Signalling cross-talk in the plant root

In plants, root architecture is responsive to environmental changes. The plant hormones cytokinin, auxin and ethylene are known to regulate root growth: cytokinin signalling, acting via type-B ARR effectors, inhibits both proliferation and elongation of root cells, while auxin promotes cell division in the root apical meristem. Various mechanisms exist by which these signalling pathways interact to enable precise spatiotemporal control of root growth. On p. 3982, G. Eric Schaller and colleagues identify another level of cross-talk between these pathways in Arabidopsis. In a screen for regulators of cytokinin-mediated root growth control, they identify mutations in the gene encoding the auxin influx carrier AUX1 that enhance the cytokinin insensitivity of arr mutants. AUX1 seems to be specifically involved in cytokinin-mediated inhibition of root cell elongation but not proliferation. Since AUX1 is required for shootward transport of auxin via the lateral root cap, the authors propose that spatial modulation of this flux controls cell elongation in this region. Moreover, they identify a negative-feedback loop in the system – with ARRs inhibiting AUX1 expression, and AUX1 promoting ARR10expression – that might set up oscillating patterns of hormone flux and gene expression in the root.

Polarisation of the self-organised optic cup

The demonstration that embryonic stem cell (ESC) cultures could self-organise into optic cup-like structures provided a striking and elegant example of the degree to which tissues and organs can self-organise. But outside the embryo context, and in the absence of more global patterning cues, can they adopt appropriate axial identity and polarity? Mototsugu Eiraku and co-workers now investigate dorsoventral (DV) patterning in in vitro formed, mouse ESC-derived optic cups (p. 3895). In vivo, DV polarity is regulated by the Wnt, Shh and BMP pathways, leading to dorsal-specific expression of Tbx5and ventral expression of Vax2. The authors find that these expression domains, and the asymmetric morphogenetic events that form the optic fissure, are largely preserved in ESC-derived optic cups, although less robustly than in vivo. Ventral identity seems to be the default status, with dorsal identity being induced by localised activation of BMP signalling. As in vivo, this is controlled by Wnt signalling, which appears to be induced specifically at the retinal/non-retinal border at one side of the forming optic cup. How this local activation of Wnt is achieved in the in vitro system is unclear, but the data presented highlight the impressive degree to which tissues can self-organise, and demonstrate the utility of this in vitro system for understanding both patterning and morphogenesis.

What do matrix metalloproteinases do in the mammary gland?

During mammary gland development, mammary epithelial tissue undergoes branching morphogenesis to invade the surrounding mammary fat pad. Morphologically, the gland is relatively simple at birth, but undergoes dramatic remodelling during puberty. Based primarily on work in vitro, the matrix metalloproteases MMP14 (MT1-MMP) and MMP15 (MT2-MMP) are thought to play key roles in this branching morphogenesis, both through protease-dependent remodelling of the extracellular matrix and through protease-independent mechanisms. By analysing early (prepubertal) postnatal mammary gland development in mice (p. 3956), Stephen Weiss and colleagues now challenge this model. They find that, in contrast to in vitro data, global deletion of MMP14 or MMP15 has no significant effect on this phase of mammary gland branching, casting doubt on the degree to which proteinase-mediated extracellular matrix remodelling is required for this morphogenetic event. However, the authors also uncover unexpected and differential roles for the two MMPs in adipose development: MMP14 deletion impairs white fat differentiation, while MMP15 mutants show enhanced beige/brown fat formation. The mechanisms underlying this remain unclear, but these data suggest that current models of the roles of these MMPs in mammary gland development may need revising.

Regulating Hh signalling with Rusc

The Hedgehog (Hh) signalling pathway plays multiple fundamental roles during development, yet despite its importance our understanding of the mechanisms regulating pathway activity is still incomplete. Jing Yang and colleagues now identify the Rusc family of RUN and SH3 domain-containing proteins as negative regulators of Hh signalling. In this study (p. 3944) Rusc2 is first identified as an interactor of Sufu – a protein that binds Gli proteins (downstream effectors of the Hh pathway) and suppresses their transcriptional activity. In cell culture, Rusc1 and Rusc2 can inhibit Hh-induced Gli activation in a Sufu-dependent manner. Upon Hh stimulation, Sufu and Gli normally dissociate, allowing Gli translocation to the nucleus. Rusc appears to form a complex with Sufu/Gli in unstimulated cells, and various lines of evidence suggest a model whereby Rusc stabilises the Sufu/Gli complex, and its dissociation upon Hh stimulation is required for Gli activation. Importantly, in vivo experiments in Xenopus embryos are consistent with Rusc1/2 acting as negative regulators of Hh signalling; knockdown of Rusc1 induces phenotypes consistent with Hh pathway overactivation. Thus, this work characterises a new component of the Hh pathway and adds to our understanding of the mechanisms underpinning Hh signal transduction.

A new view of human GnRH neurons

Reproduction in mammals is dependent on specific hypothalamic neurons secreting gonadotropin-releasing hormone (GnRH). During embryonic development, GnRH neurons originate in the nose and migrate to the brain. Here, they release GnRH into the pituitary portal blood circulation for delivery to the pituitary, thus inducing the secretion of fertility-related hormones. Although this system is well studied in mice and other mammals, very little is known about human GnRH neuron development. Here (p. 3969), Paolo Giacobini and colleagues undertake a detailed analysis of the GnRH system in first-trimester human embryos by tracking the origin, migration pattern, final destination and number of GnRH neurons. By applying 3D imaging of solvent-cleared organs (3DISCO) technology to human foetuses for the first time, the authors gain unprecedented insights into the development of the GnRH system, including identifying unexpected migratory routes and brain locations of GnRH neurons. Intriguingly, the authors find a greater number of GnRH neurons than previously thought and reveal that only approximately 20% of these cells colonise the hypothalamus by the end of the first trimester, with the rest being quite widely distributed. While the long-term fate and function of these extra-hypothalamic GnRH neurons remains unclear, their presence raises the possibility of non-fertility-related roles for the GnRH system.

Building bone around blood vessels

It is well known that, in addition to providing nutrients to growing tissues, blood vessels in the developing embryo can play more active roles in directing morphogenesis, patterning and differentiation – primarily through the secretion of signalling molecules. In bone, invasion of blood vessels precedes osteogenesis, and endothelial-derived signalling factors have been shown to regulate ossification. On p. 3933 Elazar Zelzer and co-workers now identify another role for the vasculature in controlling bone morphogenesis. They find that collagen I, the main extracellular matrix component that serves as a template for mineralisation, is deposited by osteoblasts onto endothelial cells within the bone. This is possible because, unlike most blood vessels, vessels within the developing bone are devoid of basement membrane. The collagen-coated vessels then serve as a template for mineral deposition, such that ossification spatially and temporally follows vascular patterning. Notably, disrupting vascularisation of the bone also disrupts bone deposition. This work establishes a previously unrecognised mechanism by which the vasculature regulates bone morphogenesis, and also raises a number of intriguing questions as to the mechanisms underlying the regulation of endothelial basement membrane deposition and the fate of mineralised vessels.

An interview with Paola Arlotta

Paola Arlotta is a neurodevelopmental biologist based at the Harvard Department of Stem Cell and Regenerative Biology in Boston, MA, USA. Her lab studies the birth, differentiation and assembly of neuronal circuits in the cerebral cortex with the aim of developing novel therapies for degenerative and neuropsychiatric diseases. Paola has recently become an editor for Development, and we asked her about her research and career, and her recent efforts to support women in science. See the Spotlight article.

Rebuilding a broken heart: lessons from developmental and regenerative biology

In May 2016, the annual Weinstein Cardiovascular Development and Regeneration Conference was held in Durham, North Carolina, USA. The meeting assembled leading investigators, junior scientists and trainees from around the world to discuss developmental and regenerative biological approaches to understanding the etiology of congenital heart defects and the repair of diseased cardiac tissue. In their Meeting Review, Muge Kuyumcu-Martinez and Michael Bressan present several of the major themes that were discussed throughout the meeting and highlight the depth and range of research currently being performed to uncover the causes of human cardiac diseases and develop potential therapies.

Post-transcriptional modifications in development and stem cells

Cells adapt to their environment by linking external stimuli to an intricate network of transcriptional, post-transcriptional and translational processes. Among these, mechanisms that couple environmental cues to the regulation of protein translation are not well understood. Chemical modifications of RNA allow rapid cellular responses to external stimuli by modulating a wide range of fundamental biochemical properties and processes, including the stability, splicing and translation of messenger RNA. In their  Review, Michaela Frye and Sandra Blanco focus on the occurrence of N⁶-methyladenosine (m⁶A), 5-methylcytosine (m⁵C) and pseudouridine (Ψ) in RNA, and describe how these RNA modifications are implicated in regulating pluripotency, stem cell self-renewal and fate specification.

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A post-doctoral position is available in the Franz-Odendaal Bone Development Lab to study the developmental basis of the vertebrate ocular skeleton in a comparative context. Highly motivated and independent individuals with excellent interpersonal skills are encouraged to apply. The successful applicant will take a key role in our research program which spans evo-devo, developmental genetics and phenotypic variation. Opportunities to teach undergraduates, supervise students, and outreach are available to those interested.

We are seeking a recent doctoral student in Biological Sciences or related fields with experience in Molecular Biology, Cell and Developmental Biology. Experience with zebrafish and/or chick embryos is desirable but not required. Opportunities to supervise students will be available.

Please send curriculum vitae and summary of research interests via email.
Dr Tamara Franz-Odendaal
Franz-Odendaal Bone Development Lab
Mount Saint Vincent University,
Halifax, Nova Scotia, Canada

Email: Tamara.franz-odendaal@msvu.ca

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I am looking for talented and driven candidates to apply for a position in a 4yr-PhD programme and join my laboratory at the European Cancer Stem Cell Research Institute (Cardiff University). The studentship is funded by the South-West Doctoral Training Partnership of the BBSRC and starts September 2017.

The project aims at understanding how adult stem cells respond to the local needs for cell replacement through lineage tracing, genetic manipulation, confocal microscopy, mathematical modelling and the development of a new method for the temporal control of transgene expression in Drosophila. This will be done in collaboration with Prof Helen White-Cooper’s lab in Cardiff and with Dr Edward Morrissey in Oxford.

For more details of the project see here.

Please send further questions and/or informal enquiries to Dr Joaquín de Navascués at deNavascuesJ@cardiff.ac.uk.

For details of the programme, including eligibility and expected grades of the candidates, visit the DTP website at http://www.bristol.ac.uk/swbio/

Application: http://courses.cardiff.ac.uk/funding/R2865.html

Deadline for applications: Monday 5 December 2016, midnight

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Earlier this week, I took part in a workshop on preprints – organised by Alfonso Martinez-Arias and held in Cambridge, UK. Inspired by the ASAPbio movement in the States, Alfonso felt it would be useful to bring discussion of the potential value of preprints more to the forefront in the UK. Happily, he was able to get John Inglis, co-founder of bioRxiv (the primary preprint server for the life sciences), to speak at this event, and also invited several other speakers  – including myself – to talk about their experiences with preprint servers.

If you’re interested, the whole event was live-streamed, and you can watch the video here.  But for those (understandably!) not wanting to spend 3 hours listening to people talk about preprints, here’s a (not-so-brief) summary. Or check out #pptsCamOA for the live tweeting.

If you’re not familiar with bioRxiv or preprints more generally, I’d definitely encourage you to watch John’s talk at the beginning of the video (starting around 7 minutes) – he gave a great overview of the history of bioRxiv and its potential future. One thing I find interesting is why it appears that bioRxiv is succeeding while previous efforts – most notably Nature Precedings – failed (see graph below). Presumably this is primarily because bioRxiv got its timing right: we’re in a period of changing culture with respect to science publishing, and bioRxiv is riding a wave of discontent with traditional publishing systems. Perhaps Nature Precedings just came too early, but perhaps also people have been more willing to rally behind a not-for-profit enterprise not directly linked with a publishing house (bioRxiv is supported by Cold Spring Harbor Labs not by the Press).

Image from http://asapbio.org/preprint-info/biology-preprints-over-time
Credit: Jessica Polka

As you can see from the graph, bioRxiv is expanding rapidly (now with around 450 deposits and over 1 million article accesses per month), and it’s clear to me that preprints are here to stay – though there are still a number of important challenges to address (check out the video from around 32 minutes to see where bioRxiv is going).

That preprints are becoming increasingly mainstream is also reflected in the fact that most journals are now happy to consider papers that have been posted on preprint servers – including Cell Press, who were initially and somewhat notoriously reluctant to make a clear statement on that front. Two representatives from the publishing industry talked about their attitudes to preprints – me (representing Development and The Company of Biologists) and Mark Patterson from eLife. Mark identified three reasons why eLife supports preprints: that ‘journals shouldn’t get in the way’ of what scientists want to do, that ‘journals and preprints complement each other’ and, somewhat enigmatically, that ‘new possibilities arise’. Here, Mark introduced the audience to a concept that most of the audience (myself included!) weren’t familiar with – a preprint-overlay journal. Exemplified by the maths journal Discrete Analysis, the idea here is that the journal is built on top of the preprint server, with the server (in this case arXiv) hosting the content, and the journal providing the peer review element. Later on in the workshop, Aylwyn Scally returned to this idea as his vision for how academic publishing might work in future, and it’s certainly an interesting idea…

Unlike eLife and its somewhat revolutionary ethos, The Company of Biologists is a much older and more traditional publishing enterprise, and it has taken us some time to embrace preprint servers, with each journal changing policy at different times according to feedback from its community – as shown in the excerpt from one of my slides below (I make an appearance at 56 minutes on the video). While it’s only recently that all our journals have supported preprint deposition, we’re now fully on board, and will shortly be fully integrated with bioRxiv for simple bidirectional transfer between journal and preprint server.

J2B portal is the system allowing simple transfer from the journal submission site to bioRxiv for immediate posting; B2J is the reverse portal whereby authors uploading a file to bioRxiv can easily submit to an integrated journal. 

The final speaker for the first session was Hannah Hope from the Wellcome Trust. Given that preprints allow you to get your research out to the community earlier, but that that research is not yet peer-reviewed, funding agencies have to decide whether or not to ‘count’ preprints when assessing someone’s productivity for grant or fellowship applications. The Wellcome Trust has taken a forward-looking approach to this and supports the use of preprints in applications and end-of-grant review. They’re also working with other funders to develop a common set of principles – which should be made public soon. This is great news for researchers who need to apply for a grant before their paper is formally published but who want to demonstrate that they have a good track record in their field, and hopefully will become common practice among funders!

In addition to hearing the voices of publishers and funders, Alfonso had invited several preprint users to talk about their experiences. Raymond Goldstein, an interdisciplinary PI whose work spans the physics-biology divide (and includes IgNobel prize winning work on the shape of a ponytail!), gave us the viewpoint of someone for whom posting on arXiv has been common practice for decades and for whom the surrounding angst that many biologists feel is alien. He pointed out that, with LaTeX-based formatting tools, one can generate a beautifully formatted version of the manuscript to submit to a preprint server – common practice in the physical sciences, but with most biologists still married to Microsoft Word, isn’t something we’re yet comfortable with. Raymond also raised an important question about discoverability of preprints and argued that it might make more sense to have a central server to hold everything in one place, rather than multiple outlets for preprints.

 Steve Royle told us ‘how and why I became a preprinter’ – explaining that his frustration with the amount of time it takes to get a paper published (see his blog post for some fascinating stats on this – it can be quicker to produce a baby than a paper!) induced him to start depositing preprints. As paraphrased by Richard Sever on twitter, Steve said that ‘preprints bring the joy back during the soul-destroying wait for journal publication’.  Aylwyn Scally highlighted his concerns about how the peer review system works (what credit do referees get for the work they put in?) and how he feels preprints can help change the system. Sudhakaran Prabakaran‘s unusual career path – spending time as an editor at AAAS before returning to academia to set up his own lab – has given him a unique viewpoint on academic publishing. His main point was that review takes too long (mainly because reviewers take too long!), and that preprints therefore provide a possibility to get your work out more quickly, and to take advantage of altmetrics to get your work known in the community. Finally, Brian Hendrich took to the stage to explain why he felt compelled to post a preprint to alert readers to potential problems with a published paper (something that Steve Royle also mentioned), and why he then didn’t feel the need to get that preprint formally published elsewhere.

In addition to the talks, there was a lot of discussion surrounding why preprints are useful and where we are going with them. It was great to hear some of the early career scientists express their opinions – mainly but not exclusively positive – about preprints. One expressed concern about putting her work out on a preprint server without the ‘sanity check’ of peer review, while another explained how he felt his preprint helped him get his Henry Dale Fellowship. Discussion also centred around the degree to which preprint posting can claim precedence for an idea or a set of data (though without firm conclusion!), and to what extent peer review can claim to ‘validate’ a scientific paper. In general, I found it a hugely constructive discussion, and I came away feeling positive about how preprints and journals do and can integrate to allow researchers to better disseminate their research.

At the end of my talk, I posed a bunch of questions that I hoped would provoke discussion among the audience, and I’d also be really interested to hear people’s feedback here, so please feel free to comment on any of these below!

• When should authors ideally submit to preprint server?
• Should editors be searching through preprint servers and soliciting potential submissions?
• What do preprints mean for precedent and scooping? Will researchers claim precedence through deposition of very preliminary data?
• How might this impact on e.g. data/materials sharing or patent applications?
• Is there a danger of making un-reviewed data publicly available – especially medically relevant/translational research?
• Might commenting on preprints complement or even replace traditional peer review and what would it take to make this happen?
• Is it good that we have one dominant preprint server for the life sciences or should there be several?

(9 votes)

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

Salary: £28,982-£37,768

Reference: PS10005

Closing date: 03 November 2016

Post-doctoral fellow: healthy ageing of human haematopoietic stem cells.

Fixed-term: The funds for this post are available until 31 October 2019 in the first instance.

The Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute is an international centre of excellence for stem cell research and regenerative medicine. Scientists in the Institute collaborate to advance our knowledge of various stem cell types and to perform pioneering work in translational research areas, providing the foundation for new medical treatments. The Institute currently comprises 29 research groups based across 6 sites in Cambridge. In 2018 all researchers will move to a new building on the Cambridge Biomedical Campus.

Applications are invited for a research associate to join Dr Laurenti’s group. We combine state-of-the-art experimental and computational methods to study the unique biological and molecular properties of human Haematopoietic Stem Cells (HSCs).

The post holder will join a new multidisciplinary project funded by the BBSRC. This collaboration between Dr Laurenti and Prof. Göttgens laboratories has as principal aim the investigation of the functional and molecular heterogeneity of HSCs throughout a human lifetime, with a particular focus on the effects of healthy ageing. The project will combine single cell, transcriptomics, epigenomics, flow cytometry, single cell functional assays in vitro and in vivo.

The successful candidate is expected to creatively and independently carry out their own research project, while collaborating on a regular basis with a team of experimentalists and computational biologists. They will also effectively communicate their work in writing and oral presentations at internal meetings and international conferences.

Candidates should hold a PhD in a relevant field. In particular, they will have a strong background either in stem cell biology, haematology, immunology or ageing. Extensive experience with flow cytometry, mouse models and tissue culture is required. The candidate should also possess molecular biology skills. Additional expertise with high-throughput sequencing data and the R programming language would be desirable. Finally, they will have demonstrated scientific achievement with an excellent publication record.

Once an offer of employment has been accepted, the successful candidate will be required to undergo a health assessment and a security check.

To apply online for this vacancy and to view further information about the role, please visit: http://www.jobs.cam.ac.uk/job/11327. 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.

The closing date for all applications is the Thursday 03 November 2016.

Informal enquiries are also welcome via email to: jobs@stemcells.cam.ac.uk.

Interviews will be held 09 November 2016.

Please quote reference PS10005 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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Department/Location: Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute, University of Cambridge
Reference: PS10545
Closing date: 05 January 2017
Studentships starting October 2017

http://www.stemcells.cam.ac.uk/study/wtprogramme/

Stem Cell Biology

Stem cells are defined by the dual capacity to self-renew and to differentiate. These properties sustain homeostatic cell turnover in adult tissues and enable repair and regeneration throughout the lifetime of the organism. In contrast, pluripotent stem cells are generated in the laboratory from early embryos or by molecular reprogramming. They have the capacity to make any somatic cell type, including tissue stem cells.
Stem cell biology aims to identify and characterise which cells are true stem cells, and to elucidate the physiological, cellular and molecular mechanisms that govern self-renewal, fate specification and differentiation. This research should provide new foundations for biomedical discovery, biotechnological and biopharmaceutical exploitation, and clinical applications in regenerative medicine.

Cambridge Stem Cell Community

The University of Cambridge is exceptional in the depth and diversity of its research in Stem Cell Biology, and has a dynamic and interactive research community that is ranked amongst the foremost in the world. By bringing together members of both the Schools of Biology and Medicine, this four year PhD programme will enable you to take advantage of the strength and breadth of stem cell research available in Cambridge. Choose from over 50 participating host laboratories using a range of experimental approaches and organisms.

Programme Outline

During the first year students will:
• Perform laboratory rotations in three different participating groups working on both basic and translational stem cell biology.
• Study fundamental aspects of Stem Cell Biology through a series of teaching modules led by leaders in the field.
• Learn a variety of techniques, such as advanced imaging, flow cytometry, and management of complex data sets.

Students are expected to choose a laboratory for their thesis research by June 2018, and will then write a research proposal to be assessed for the MRes Degree in Stem Cell Biology. This assessment will also be used to determine whether students continue on to a 3-year PhD.

Application Process

Visit http://www.stemcells.cam.ac.uk/study/wtprogramme/ for further details including how to apply. Please note: you will be required to complete and submit a departmental application form, provide two references and upload copies of your transcripts as part of the application process.

We invite applications from both EU and Non-EU applicants*.

Application Deadline: Thursday 5th January 2017 Interviews will be held on: 23rd, 24th and 25th January 2017

*Non-EU applicants, who need to apply for additional funding (which covers tuition fees at the ‘overseas’ rate), must also apply through the University Graduate Student Application Form ‘Applicant Portal’ by Wednesday 7th December 2016.

Informal enquiries are also welcome via email to sci-phd@stemcells.cam.ac.uk.

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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We are looking for highly motivated and talented candidates for a 4yr-PhD programme in the laboratory of Dr Toki Takahashi at the University of Manchester. This studentship is funded by the BBSRC DTP and will start in September 2017. The overall aim of the project is to understand how our head is formed by combining a laboratory experimental approach with high-throughput bioinformatics analysis. This project is in collaboration with Dr Shane Herbert and Professor Magnus Rattray.

The vertebrate craniofacial development is a remarkably dynamic and intricate process, requiring the tightly regulated growth, migration and patterning of a particular cell population, cranial neural crest cells (CNC). For this reason, craniofacial malformations are among the most common, accounting for one third of human congenital defects. Whilst the causes of most cases are unknown, several clinical studies reported the mutations within Alx homeobox genes in recessive hereditary cases (ALX-related frontonasal dysplasia; ALX-FND). Our lab reported a new function of alx1 gene in frontonasal CNC migration, and demonstrated that alx1 is critical to zebrafish craniofacial development.

In this project, we will first establish a zebrafish model of ALX-FND by generating alx1 null mutant line with the CRISPR/Cas9 system. Using the real-time image analysis of this mutant, we will examine in details how alx1 controls the CNC migration. Furthermore, we will purify the migrating CNC from the mutant by FACS for deep sequencing of transcriptomes. Bioinformatics analysis from this targeted cell population will identify the downstream targets of alx1. By integrating the high-throughput data and the live image profiling of CNC migration into computer modelling, the project will elucidate the new alx1 gene regulatory network controlling vertebrate head development.

For further details and information on how to apply, visit the University of Manchester DTP studentships website at http://www.dtpstudentships.ls.manchester.ac.uk/

Deadline for applications: Friday 18 November 2016, 5pm

Informal enquiries can be made to Dr Toki Takahashi at Tokiharu.Takahashi@manchester.ac.uk

(3 votes)

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The Laboratory of Zebrafish Developmental Genomics headed by Cecilia L. Winata was established in partnership with the Max Planck Institute for Heart and Lung Research (MPI-HLR). The focus of our research is to elucidate the gene regulatory networks and epigenetic mechanisms regulating various aspects of developmental biology as the initial step towards understanding human genetic diseases. Our research employs state of the art methodology based on Next-Generation Sequencing as well as CRISPR/Cas9 genome editing technology.

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