IRIBHM is a research institute of the Medical School of the Free University of Brussels (Université Libre de Bruxelles, ULB). The institute offers an internationally prominent research environment in molecular biology and life sciences, that engage different topics that span receptor pharmacology and new therapeutic targets discovery, early embryonic development, neurobiology, stem cells and cancer. The institute has trained over the years a number of talented young scientists both at the graduate and postdoctoral levels. In order to expand internationally and keep rising its level of excellence, the IRIBHM launches an international graduate programme in order to prepare the future leaders in biomedical sciences.
At least 2 PhD scholarships are available. The successful candidates will have the opportunity to work in a warm and stimulating research environment aligned with the highest international standards.
As the administrative center of the European Union, Brussels is a perfect location for an International PhD programme. In addition, the city shows an active cultural life and is hosting most nationalities from all over the world.
Closing date for application is April 28, 2019. The short-listed candidates will be invited for an interview, which will be held in Brussels (between June 3 and 4, 2019). Accepted candidates are expected to start their research project on November 1st, 2019.
To find out more about the IRIBHM International PhD Program, please visit our web site at http://iribhmphd.ulb.be
CamBioScience Limited is a premium global provider of education and educational technology. The Courses & Conferences Department works with world-leading experts to provide intensive training courses and conferences. Courses are in a broad spectrum of emerging and established life science technologies for academic and industry professionals. In-Person courses and conferences take place in various locations around the world including United Kingdom, Austria, South Korea and China.
CamBioScience Ltd. are looking for a highly-motivated, outgoing and ambitious person who will sell in-person courses and conferences to life science researchers. The position will be full- or part- time.
We have courses in the developmental biology field including organoids and gastruloids. You will also have the opportunity to attend these courses to see how they are organised and delivered.
Please contact: michelle@cambioscience.com if you have any questions and for information on how to apply.
At the beginning of November 2018, thirty researchers congregated at Wiston House to attend a workshop titled ‘Evo-chromo: towards an integrative approach of chromatin dynamics across eukaryotes’. The workshop was organised by Frederic Berger (Gregor Mendel Institute) and Ines Anna Drinnenberg (Institut Curie), and was the 27th workshop hosted by The Company of Biologists since 2010. Its objective was to explore the biology of chromatin – the macromolecular complex of DNA, RNA and protein that makes up chromosomes – in light of evolutionary questions and ideas, particularly those relating to eukaryotic evolution.
Chromatin was first observed in the 19th century, when it was visualised by staining chromatin with basic dyes (the term ‘chromatin’ derives from the Greek word khroma meaning ‘colour’). During the molecular biology revolution of the 20th century, chromatin came to sit at the heart of our understanding of gene regulation, cell differentiation and inheritance. As our discussions at the meeting highlighted, the increasing wealth of phylogenetic data, exciting new technologies, and an increasing number of tractable model systems has produced a series of puzzling and pressing evolutionary questions. However, in the excitement and industry of modern molecular biology, these questions often remain skulking in the background. The focus of this meeting was to clarify those questions and bring them to the foreground.
Alongside the 20 invited speakers, we were lucky enough to attend as one of 10 early-career researchers (PhD students, postdocs, and young PIs). These places are fully funded by the Company of Biologists, and it was a fantastic opportunity for us to present our work and receive feedback. Alexander is a graduate student in the Henderson Group (University of Cambridge) specialising in plant meiotic recombination, and James is postdoc in the Rentzsch Group (Sars Centre) specialising in cnidarian development and evolution. This was an incredibly valuable opportunity for us to meet world-class scientists and expand our academic network. Furthermore, as we are both planning to move deeper into the world of chromatin biology, it was even more valuable in helping us to better orientate in this research area and gain an understanding of the most pertinent questions in the field.
Back row standing: Harmit Malik, Kenneth Wolfe, Peter Andersen, Ulrich Technau, Aidan Maartens, Tobias Wernecke, Simon Elsässer, James Briscoe, Peter Sarkies, Zachary Harvey. Middle row standing: Brandon Gaut, Chema Martin-Duran, James Gahan, Siavash Kurdistani, Frederic Berger, Steven Henikoff, Bob Schmitz, Catherine Peichel, Alexander (Sasha) Blackwell, Douglas Erwin, Bernardo Lemos. Front row seated: Juan Ausio, Joe Thornton, Mia Levine, Kinga Rutowicz, Ines Anna Drinnenberg, Karolin Luger, Marilyn Renfree, Joyce Kao, Wendy Bickmore
The workshop was far from regular. Firstly, we had never attended a meeting that was both so small and so diverse. Talks ranged from genomic imprinting in marsupials, developing biomarkers of human aging, the structure of archaeal nucleosomes, developing quantitative ChIP-seq methods, and the role of genetic conflict in centromere evolution. However, all of these diverse research areas were looked at through the lens of evolutionary biology, with the objective to find commonalities and shared general questions. One consequence of this diversity was that everyone was there to learn and to think, as everybody was to some extent outside of their comfort zone. Secondly, the fact that we were all there to address the issue of chromatin evolution meant that we searched for the common threads and broader significance connecting the talks. This led to a greater examination of the conceptual framework(s) surrounding chromatin biology, and a probing of the limitations and future possibilities. Personally, we found the meeting to be pleasingly free of the ‘look-how-many-RNA-seq-experiments-I-did’ kind of attitude, and the focus was almost exclusively centred on biology and ideas. This was reflected in the large amount of preliminary and unpublished data shown at the meeting. Thirdly, alongside the marvellous attendees, the house itself, located in West Sussex, provided a wonderful context. The 16th century house is situated in the South Downs National Park, and is the location of Wilton Park, a project established in 1946 with the aim of promoting peace and democracy in Europe. It therefore seemed an appropriate setting for the meeting, given the role that international science has played in promoting integration and cooperation in a once fractured world. This couldn’t help but feel more poignant, given the current resurgence of nationalism and the risks this poses to science. Indeed, perhaps the stand out speaker of the meeting was not a scientist but rather a local historian who led us on a captivating historical tour of the house.
The small size of the conference, the absence of phone signal and the remote location all encouraged meaningful social interaction. There was a chance to engage with everybody, with no shortage of time for discussion and questions. The organisers aimed to restrict the number of attendees known by each attendee – this had the benefit of promoting interaction, an unpretentious attitude, and removed the usual hierarchies emerging at most more specialised conferences. This lack of hierarchy was further demonstrated by every speaker having equal time. Interaction was stimulated by having a table plan for all of the dinners, which was rearranged each night. Altogether, the quality of organisation and the thought put into every detail was mindboggling.
It is our belief that this meeting was a milestone in the development of chromatin biology. From our perspective, a consistent problem is that the worlds of ‘mechanism’ and ‘theory’ rarely interact in meaningful ways; the former either disregarding the latter, or else having a problematically naïve understanding of their concepts, whilst the latter remain behind with experimental advances and have a tendency of gross oversimplification. This meeting was at least a step towards redressing this balance, and felt very much like the beginning of a connection between the two. Hopefully, this will be strengthened by continued meetings and interactions of this kind.
As early stage researchers, we left feeling inspired to move deeper into the field of chromatin biology and more than ever convinced that there are huge questions left to be answered. We thoroughly recommend early career researchers to apply to one of these workshops in the future (for a list of upcoming workshops go to http://www.biologists.com/workshops/). If you are interested to read more about the questions discussed and identified during the meeting, please take a look at the forthcoming perspective article – watch this space!
The Node’s Aidan Maartens and The Company of Biologists’ Meetings Organiser Nicky Le Blond also made a film during the event. See what the organisers and participants had to say about this successful Workshop here:
Welcome to our monthly trawl for developmental biology (and related) preprints.
February was notable for the amount of neural development, from retina to cortex and fly to fish. We also found butterfly wings, human segmentation, a plenitude of of plants and sequenced genomes for komodo dragons, parasitic wasps, copepods and one celebrity cat.
The preprints were hosted on bioRxiv, PeerJ, andarXiv. Let us know if we missed anything, and use these links to get to the section you want:
A neurodevelopmental origin of behavioral individuality
Gerit Linneweber, Maheva Andriatsilavo, Suchetana Dutta, Liz Hellbruegge, Guangda Liu, Radoslaw Ejsmont, Lisa Fenk, Andrew Straw, Mathias Wernet, Peter Robin Hiesinger, Bassem Hassan
Dynamic chromatin targeting of BRD4 stimulates cardiac fibroblast activation
Matthew S Stratton, Rushita A Bagchi, Rachel A Hirsch, Andrew S Riching, Marina B Felisbino, Blake Y Enyart, Keith A Koch, Maria A Cavasin, Michael Alexanian, Kunhua Song, Jun Qi, Madeleine E Lemieux, Maggie P.Y. Lam, Saptarsi M Haldar, Charles Y Lin, Timothy McKinsey
Active wetting of epithelial tissues
Carlos Pérez-González, Ricard Alert, Carles Blanch-Mercader, Manuel Gómez-González, Tomasz Kolodziej, Elsa Bazellières, Jaume Casademunt, Xavier Trepat
Dynamics of microRNA expression during mouse prenatal development
Sorena Rahmanian, Rabi Murad, Alessandra Breschi, Weihua Zeng, Brian A Williams, Mark Mackiewicz, Brian Roberts, Sarah Meadows, Dianne Moore, Carrie Davis, Diane Trout, Chris Zaleski, Alexander Dobin, Lei-Hoon Sei, Jorg Drenkow, Alex Scavelli, Thomas R Gingeras, Barbara Wold, Richard M. Myers, Roderic Guigo, Ali Mortazavi
Zebrafish vasculature from Jung, et al.’s preprint
The Tug1 Locus is Essential for Male Fertility
Jordan P. Lewandowski, Gabrijela Dumbović, Audrey R. Watson, Taeyoung Hwang, Emily Jacobs-Palmer, Nydia Chang, Christian Much, Kyle Turner, Christopher Kirby, Jana Felicitas Schulz, Clara-Louisa Müller, Nimrod D. Rubinstein, Abigail F. Groff, Steve C. Liapis, Chiara Gerhardinger, Norbert Hubner, Sebastiaan van Heesch, Hopi E. Hoekstra, Martin Sauvageau, John L. Rinn
Computer models of facial feature diversity in Qiu, et al.’s preprint
Oligogenic effects of 16p11.2 copy number variation on craniofacial development
Yuqi Qiu, Thomas Arbogast, Sandra Martin Lorenzo, Hongying Li, Tang Shih, Richardson Ellen, Oanh Hong, Shawn Cho, Omar Shanta, Pang Timothy, Christina Corsello, Curtis K. Deutsch, Claire Chevalier, Erica E Davis, Lilia M Iakoucheva, Yann Herault, Nicholas Katasanis, Karen Messer, Jonathan Sebat
SURF1 mutations causative of Leigh syndrome impair human neurogenesis
Gizem Inak, Agnieszka Rybak-Wolf, Pawel Lisowski, Rene Juettner, Annika Zink, Barbara Mlody, Petar Glazar, Christopher Secker, Ummi H. Ciptasari, Werner Stenzel, Tobias Hahn, Sebastian Diecke, Josef Priller, Michael Gotthardt, Ralf Kuehn, Erich E. Wanker, Nikolaus Rajewsky, Markus Schuelke, Alessandro Prigione
A newly-sequenced Komodo dragon from Lind, et al.’s preprint
A high-resolution, chromosome-assigned Komodo dragon genome reveals adaptations in the cardiovascular, muscular, and chemosensory systems of monitor lizards
Abigail Lind, Yvonne Y.Y. Lai, Yulia Mostovoy, Alisha K Holloway, Alessio Iannucci, Angel CY Mak, Marco Fondi, Valerio Orlandini, Walter L Eckalbar, Massimo Milan, Michail Rovatsos, Ilya G. Kichigin, Alex I Makunin, Martina Pokorna, Marie Altmanova, Vladimir Trifonov, Elio Schijlen, Lukas Kratochvil, Renato Fani, Tim S Jessop, Tomaso Patarnello, James W Hicks, Oliver A. Ryder, Joseph R. Mendelson III, Claudio Ciofi, Pui-Yan A. Kwok, Katherine S Pollard, Benoit Bruneau
High-density spatial transcriptomics arrays for in situ tissue profiling
Sanja Vickovic, Goekcen Eraslan, Johanna Klughammer, Linnea Stenbeck, Fredrik Salmen, Tarmo Aijo, Richard Bonneau, Ludvig Bergenstraahle, Joshua Gould, Mostafa Ronaghi, Jonas Frisen, Joakim Lundeberg, Aviv Regev, Patrik L Staahl
An Interscholastic Network to Generate LexA Enhancer Trap Lines in Drosophila
Lutz Kockel, Catherine Griffin, Yaseen Ahmed, Lauren Fidelak, Arjun Rajan, Ethan P. Gould, Miles Haigney, Benjamin Ralston, Rex J. Tercek, Lara Galligani, Sagar Rao, Lutfi Huq, Hersh K. Bhargava, Ailis C. Dooner, Emily G. Lemmerman, Ruby F. Malusa, Tran H. Nguyen, Julie S. Chung, Sara M. Gregory, Kiyomasa M. Kuwana, Jonathan T. Regenold, Alexander Wei, Jake Ashton, Patrick Dickinson, Kate Martel, Connie Cai, Carissa Chen, Stephen Price, Jeffrey Qiao, David Shepley, Joanna Zhang, Meghana Chalasani, Khanh Nguyen, August Aalto, ByungJun Kim, Erik Tazawa-Goodchild, Amanda Sherwood, Ahmad Rahman, Sum Ying Celeste Wu, Joel Lotzkar, Serena Michaels, Hillary Aristotle, Antigone Clark, Grace Gasper, Evan Xiang, Frieda Luna Schlor, Melissa Lu, Kate Haering, Julia Friberg, Alyssa Kuwana, Jonathan Lee, Alan Liu, Emma Norton, Leena Hamad, Clara Lee, Dara Okeremi, Harry diTullio, Kat Dumoulin, Sun Yu Gordon Chi, Grayson S. Derossi, Rose E. Horowitch, Elias C. Issa, Dan T. Le, Bryce C. Morales, Ayush Noori, Justin Shao, Sophia Cho, Mai N. Hoang, Ian M. Johnson, Katherine C. Lee, Maria Lee, Elizabeth A. Madamidola, Katrina E. Schmitt, Gabriel Byan, Taeyoung Park, Jonathan Chen, Alexi Monovoukas, Madison J. Kang, Tanner McGowan, Joseph J. Walewski, Brennan Simon, Sophia J. Zu, Gregory P. Miller, Kate B. Fitzpatrick, Nicole Lantz, Elizabeth Fox, Jeanette Collette, Richard Kurtz, Chris Duncan, Ryan Palmer, Cheryl Rotondo, Eric Janicki, Townley Chisholm, Anne Rankin, Sangbin Park, Seung K. Kim
Multi-immersion open-top light-sheet microscope for high-throughput imaging of cleared tissues
Adam K. Glaser, Nicholas P. Reder, Ye Chen, Chengbo Yin, Linpeng Wei, Soyoung Kang, Lindsey A. Barner, Weisi Xie, Erin F. McCarty, Chenyi Mao, Aaron R. Halpern, Caleb R. Stoltzfus, Jonathan S. Daniels, Michael Y. Gerner, Philip R Nicovich, Joshua C. Vaughan, Lawrence D. True, Jonathan T.C. Liu
Perceptions and Prospects in Life Sciences in a Heterogeneous Latin American Population
Leonardo M.R. Ferreira, Giovanni A. Carosso, Bruno Lopez-Videla, Gustavo Vaca Diez, Laura Ines Rivera-Betancourt, Yara Rodriguez, Dalila G. Ordonez, Natalia Montellano Duran, Diana K. Alatriste-Gonzalez, Aldo Vacaflores, Soad Bohorquez, Lilian Gonzalez Auza, Christian Schuetz, Carolina Alexander-Savino, Omar Gandarilla Cuellar, Mohammed Andres Mostajo Radji
Allison Bardin’s Lab Institut Curie, Dept. of Genetics and Developmental Biology Paris, FR In collaboration with
Nicolas Servant’s Group Institut Curie,
Dept. of Bioinformatics, Paris, FR
Maintaining genome integrity of adult stem cells is important to prevent cancer initiation and stem cell functional decline during aging. We have found that a surprising level of genome instability arises during aging in adult intestinal stem cells of Drosophila (Siudeja, Cell Stem Cell, 2015). This model provides an excellent system in which to address important fundamental questions of how stem cell genomes are maintained. The bioinformatic project will further investigate sequencing data to understand stem cell genome instability using Drosophila genetics and whole-genome sequencing approaches.
We are seeking enthusiastic, collaborative, and highly motivated candidates to join us in our genomic analyses. In particular the recruited person will develop new Nanopore-based pipelines and analyses methodologies. In addition, the bioinformatician will analyse genomic variants (structural variants, single nucleotide variants, de novo transposon insertions) and DamID data from Illumina sequencing using pipelines we have already developed in the lab (https://github.com/bardin-lab/.
Candidates with Master’s or PhD degrees may apply. Experience in NGS sequencing analysis is required. General knowledge of biology and expertise in R, Python, Galaxy, and git would be appreciated.
Our team is situated within a new, dynamic, international department with state-of-the-art imaging, sequencing, and proteomics facilities at the Institut Curie in the heart of downtown Paris. To apply, please send your CV, cover letter, and names of two references to allison.bardin@curie.fr.
Website: https://science.institut-curie.org/research/biology-cancer-genetics-and-epigenetics/developmental-biology-and-genetics/team-bardin/
Fixed term contract (available now until 30th September 2019); Full time preferred
Salary: Grade 5 – £25,482/ year
Deadline for applications: 10th March 2019
A Brain Tumour Research-sponsored research assistant position for a motivated scientist is available in the laboratory of Dr. Claudia Barros at the Peninsula School of Medicine of the University of Plymouth, UK. You will be responsible to provide research support to a project focused on the characterization of identified novel target genes potentially involved in brain tumour initiation and growth, and contribute to laboratory maintenance. The work includes molecular biology, cellular and biochemical techniques, such as gene loss and gain of function assays in vivo and in vitro, RT-qPCR, immunochemistry, western-blotting and confocal imaging. It makes use of Drosophila as in vivo model and human brain tumour cell lines and tissues. A relevant 1st class or minimum 2:1 (or equivalent) Bachelor degree is required. A postgraduate Research degree or extended related research experience may be preferred. Experience in as many of the mentioned techniques is desired. Reliability, organisation, ability to multitask and collaborate with team members are essential.
Please include in your application a brief cover letter detailing suitability, experience and interest, an academic CV and ensure that at least one academic reference is received.
In this episode from our series exploring 100 ideas in genetics, we’re entering the glamorous world of modelling, meeting the supermodels… of science. We’re taking a look at some of the field’s top models – the eclectic collection of organisms that have been put to work in the lab to reveal the secrets of biology.
We’ve picked out the fruit fly, mouse and Arabidopsis as our top models – but what would be yours?
If you enjoy the show, please do rate and review and spread the word. And you can always send feedback and suggestions for future episodes and guests to podcast@geneticsunzipped.com
While many vertebrates have multiple sets of teeth over their lifetime, some, like humans, have just a single set of replacement teeth (diphydonty), while others, like mice, manage with a single set (monophydonty). This diversity raises both evolutionary questions – how did different tooth replacement strategies evolve? – and developmental ones – what mechanisms prevent replacement teeth in animals that have lost them? A new paper in Development tackles these questions with a molecular analysis of mouse tooth development. We caught up with first author Elena Popa and her supervisor Abigail Tucker, Professor of Development and Evolution at King’s College London, to find out more about the work.
Elena and Abigail.
Abigail, can you give us your scientific biography and the questions your lab is trying to answer?
AT My lab is interested in how bodies are formed during development, both from a clinical perspective of understanding birth defects, but also from the point of view of understanding how evolution has shaped our bodies. I started out investigating tadpole tail development for my PhD with Jonathan Slack and then swapped ends and moved to the head for my first postdoc with Paul Sharpe. Here, I investigated how the face and dentition are patterned. This is where I first encountered tooth development, and although I have moved on to study the cranial neural crest, the jaw, cranial glands and ear, I have always kept some experiments going to understand more about the tooth. Teeth are often the only thing left preserved in the fossil record, so they have a central importance to our understanding of evolution. There are still lots of unanswered questions, such as what regulates tooth number, tooth size and tooth shape? It’s a great model for understanding epithelial-mesenchymal interactions, as both tissues are integral to the formation of the final tooth but take it in turns to play the leading role.
Elena, how did you come to join the Tucker lab and what drives your research?
EP Developmental biology was by far my favourite subject during my undergraduate years at Royal Holloway. I didn’t know it was going to be tooth development in particular back then, but as soon as I read about Professor Abigail Tucker’s research I was completely captivated. Her lab provided the opportunity to perform a comparative study of molecular interactions and developmental processes that allow or disrupt tooth replacement in a wide variety of vertebrates. Why can’t we have more than two sets of teeth but snakes can? This was essentially the question that drove my research in the Tucker lab.
What initially led you to try and ‘reawaken’ tooth replacement in the mouse?
EP Why the potential for tooth replacement varies so much across vertebrates is an intriguing question. Having performed an in-depth study of the development of the dental lamina in many different animal models, we suspected that this structure retains the capacity to give rise to a subsequent generation of teeth, even in the molar region of the mouse (the mouse only has one generation of teeth and molars, in general, do not replace). The dental lamina next to the first molar can be seen protruding at E16.5 but disappears soon after birth, and has been termed the rudimentary successional dental lamina (RSDL). We compared the RSDL with the successional lamina of the minipig (which gives rise to a second generation tooth), and found that both expressed the epithelial stem cell marker Sox2; however, Wnt activity was only present in the minipig lamina. Knowing that stimulating Wnt signalling by means of different transgenic lines leads to the formation of supernumerary teeth, we based our experimental design on these comparisons, aiming to recapitulate tooth replacement in the mouse.
Can you give us the key results of the paper in a paragraph?
EP & AT Our results show that, although the mouse normally does not form a second replacement set of teeth, it still has the potential to do so if given the right signals. Stimulation of Wnt signalling in the rudimentary replacement lamina in transgenic mice or isolation of the lamina in culture both led to the formation of a new tooth. We started by showing that the RSDL exhibits molecular similarities to the competent dental lamina in a diphyodont mammal and retains odontogenic capacity, which we were able to reawaken by selectively inducing Sox2+ cells to activate canonical Wnt/β-catenin signalling. We were able to confirm the dental identity of the structures that arose from the RSDL in the mutant mice by performing in situ hybridization for genes known to be expressed during normal tooth development. The mutant RSDL was also highly proliferative and gave rise to multiple ectopic teeth, many of which were complex in shape and mineralised after transplantation in kidney capsule. We also uncovered an inhibitory relationship between Wnt signalling and Sox2, where ectopic stimulation of Wnt signalling leads to downregulation of Sox2 expression.
New tooth formation from the RSDL, showing Sox9 expression.
When you remove the first-generation tooth, this frees the RSDL to form a tooth bud. How is this potential inhibited in the context of normal development?
EP & AT Tooth number has previously been shown to be controlled by a balance between activators and inhibitors, creating an inhibitory cascade. For example, in many mammals three molars form at the back of the mouth by serial addition from a single molar placode. If the primordium for the subsequent molars is separated from the murine first molar in culture, the second molar initiates development faster and grows to a larger size than if left intact. The first molar therefore appears to be controlling the development of the next tooth in the series. In the shrew, the first generation of teeth initiate but then regress and are replaced by the permanent set of teeth. Here, again, it has been suggested that early formation of the permanent teeth might inhibit the development of the first set: timing and spatial arrangement of tooth germs is therefore clearly important in the control of final tooth number.
In our paper, we show that the RSDL has the potential to form a tooth and speculate that the adjacent molar sends a Wnt-inhibitory signal to the surrounding dental tissue. This then prevents Wnt activity in the RSDL, and leads to its regression. This is relevant to human tooth replacement, as structures similar to the RSDL have been identified next to the permanent teeth during development. In normal development of our dentition, therefore, the permanent tooth may inhibit the generation of a third set of teeth.
Wnt signalling leads to a reduction in Sox2 in the dental epithelium but not associated epithelia – what makes this relationship context dependent?
AT The context-dependent nature of the relationship between Wnts and Sox2 was very striking. This fits, however, with the literature, which has shown similar context-dependent interactions. For example, in the airway submucosa, Sox2 has both an inductive and a repressive effect on Wnt signalling that is dependent on the presence of other factors, whereas in the lung Wnts inhibit Sox2 but only at early stages of development. In the tooth, the repression of Sox2 by Wnts might be dependent on other factors with dynamic temporal and spatial expression patterns. It will be very intriguing to work out what these factors might be.
Do you know of any evolutionary scenarios where monophyodonty transitioned to diphyodonty, and if so does this involve a similar revitalisation to that you have discovered in the mouse?
EP & AT Throughout evolution, the general trend is one where animals reduce the number of tooth generations in favour of more-complex tooth shapes and better occlusion. As in the mouse, there is often evidence of a rudimentary structure, which points to this reduction in number. For example, we have shown that in the diphyodont fruit bat, the canine shows evidence of a third generation as it displayed a vestigial structure homologous to the mouse RSDL next to the second-generation tooth. In nature, there are rare cases proposed where teeth have been lost and then reappear, e.g. in the frog Gastrotheca guentheri, where teeth are found on the lower jaw but are absent in all other frogs. This would suggest that rudimentary tooth structures can be reawakened not just in the lab.
Did the research include any particular result or eureka moment that has stuck with you?
AT For me the eureka moment was when we generated a tooth germ from the RSDL by simply cutting off the main tooth. Really it’s a simple experiment but has a key message, which is that the reason a mouse doesn’t have a second set of teeth is that the first generation of teeth inhibits this from happening. This has important consequences, as it means that if this inhibition could be lifted an extra set of teeth might be possible.
And what about the flipside: any moments of frustration or despair?
EP For my PhD I worked with a lot of non-model organisms (bats, geckos, guinea pigs, opossum) in addition to the minipig and mouse shown here. These samples were always much more difficult to obtain and every time you wanted to look at gene expression it meant cloning, so things took much longer than expected. In addition, the anti-Sox2 antibody has been a particularly tricky to work with across species. Considering that it is at the core of my research, it became frustrating when it simply refused to work. After what felt like hundreds of failed attempts, finally being able to see Sox2 staining under the microscope felt like a huge relief!
After what felt like hundreds of failed attempts, finally being able to see Sox2 staining under the microscope felt like a huge relief!
So what next for you after this paper?
EP I have loved my time in science and particularly in the Tucker lab, where I had the opportunity to learn a great deal and diversify my wet lab skillset beyond what I could have ever hoped for. I’ve now shifted my focus to science media production, observing and documenting scientific discoveries from behind a camera lens.
Where will this work take the Tucker lab?
AT For me the next question is what signals from the first tooth stop the second generation forming? Our results predict that such signals prevent canonical Wnt signalling from being activated in the RSDL. Expression patterns predict possible roles for dickkopf 2 and dickkopf 3 that could be tested in culture or in vivo. Another avenue is the vestibular lamina. This is a really understudied structure but appears to have the potential to form teeth when stimulated by Wnt signalling. I am really interested in the relationship between the dental lamina and vestibular lamina, as these two epithelial structures are united during early development, forming from the same placode. What signals determine whether you become a dental lamina and form teeth, or a vestibular lamina and form the cheek ridge, is next on my list.
Finally, let’s move outside the lab – what do you like to do in your spare time in London?
EB I think the UK is an incredibly beautiful country, so I tend to spend most of my free time travelling and exploring its fantastic landscapes. My favourite places to go are Cornwall and the Lake District. I also have a characterful little Whippet puppy, who takes up a lot of my time at the moment!
AT I commute into London from Kent where I live with my husband, children, cat, bearded dragon and five snakes. I love London, having grown up there, but have become a convert to the countryside. I love cooking, eating and travel, and am writing this from the Atacama desert in Chile.
The Miller lab is seeking a highly motivated, organized and enthusiastic postdoctoral fellow to study embryonic kidney development and its relationship to kidney pathologies, including cystic kidney diseases and cancer. We are interested in the role of Wnt signaling in shaping nephric tubules, utilizing Xenopus (frog) embryos and mammalian tissue culture as models. Current goals include: 1) Determining how junctions are formed during tubule formation; 2) Modeling how patient mutations result in human developmental kidney diseases; 3) Discovering novel components affecting nephron development; 4) Visualizing in vivo tube formation using advanced live imaging techniques; 5) Generating transgenic animals to visualize nephrogenesis in vivo
Current projects utilize developmental, molecular and cell biological approaches including imaging in living embryos. Applicants with a Ph.D., M.D. or equivalent and a strong background in Developmental Biology, Embryology, Cell Biology, Molecular Biology and/or Stem Cell Biology are highly encouraged to apply. Salary and benefits are commensurate with relevant experience. Review of applications will continue until the position has been filled.
Please send your CV, cover letter indicating current and future research interests, and the name/email address of three references to:
In the summer of 2018, two commentaries from the Science Media Center (anopen letter from Chief Executive Fiona Fox and a‘World View’ in Nature news by Senior Press Manager Tom Sheldon) voiced concerns about how preprints in the life sciences could pose a potential threat to science reporting in the mass media. These articles initiated (often heated) debates within the scientific community, underlining the need for public discussions between researchers, press officers and journalists. Open Research London, a London collective of academics and librarians, and the Open Access team at the Francis Crick Institute, led by Head Librarian Frank Norman, collaborated to nucleate a platform for such discussions through an evening event at the Crick on the 6th of February.
Jane Hughes, Director of Communications at the Crick and chair of the event, kicked off the evening by asking a large audience whether they think preprints need to change or, instead, whether science reporting must adapt – with an overwhelming show of hands for the latter option.
This set the stage for Tom Sheldon, who acknowledged that preprints have been tremendously useful for science, but warned about unforeseen side-effects – such as a potential dismantling of the press embargo system. He made a strong case for preserving embargoes: for accuracy, as they give journalists time to assess claims and solicit expert comment, and for impact, ensuring maximal reach for important findings. In the case of acontroversial study claiming that genetically modified maize and Roundup can cause tumours and early death in rats (since retracted), he pointed out that embargo policies gave journalists the time to consult experts, who were quick to identify significant flaws in the study. As a result, many articles in the mass media (e.g. BBC and Reuters) reported the scepticism surrounding the research. Sheldon noted that if the criticism had followed the breaking news, it would have been too late, buried by the next news cycle. In a second example, a major clinical trial showed that e-cigarettes are more effective than nicotine replacement therapies in helping smokers to quit. In this case, the embargo helped these findings make it to the front page of multiple newspapers simultaneously, maximising impact.
Sheldon then went on to envisage how such stories concerning human health might have been covered had the study been posted as a preprint. In the first hypothetical, he argued a journalist might have rushed to cover a study without consulting experts, thereby misinforming the public. In the second hypothetical, initial reporting on the preprint might have made an embargo pointless or incompatible with journal policies- meaning the story would never make it to multiple news outlets, leaving the public uninformed about important results. Sheldon then concluded that preprints necessarily disrupt the current system and – even though there have so far been no examples of preprints causing damage – we must ensure that the public understanding of science is not a casualty. In his opinion, we cannot expect journalists to change, and it is publishers, scientists and press officers who carry the responsibility to adapt.
Clare Ryan, Head of Media Relations at the Wellcome Trust, shared Sheldon’s view that we won’t be able to change journalism, and should aspire to influence press officers, scientists and journals instead. In her talk, she suggested that the focus of science news should shift away from journal papers. After using a clip from John Oliver’s popular weekly show to showcase some major issues with science news, she went on to explain her vision of science in the media. Instead of forcing each ‘new discovery’ into the spotlight of the daily news (which doesn’t reflect the gradual, self-correcting nature of scientific progress in real life), journalists could aim to include more personality, complexity, and also disagreement in their stories. ‘Science is more War and Peace than David Copperfield’, after all, and we should seek to give the public better insights into how science really works. She ended with some practical advice, including ‘stop writing so many press releases!’, a sentiment that resonated strongly with the audience. Later in the Q&A session, Fiona Fox also emphasized that press officers should never write a press release about a preprint.
Slide from Clare Ryan’s talk
Robin Lovell-Badge, Senior Group Leader at the Francis Crick Institute, shifted the discussion towards the values of preprints in his talk titled ‘Preprints are the future’. After calling out some limitations of traditional journal publishing (such as cost, speed, and a peer-review process that doesn’t work too well), he also gave several examples of big studies published in the top journals, which later had to be retracted (e.g. the fraudulent Wakefield study on the link between MMR vaccines and autism), arguing that just because something is peer-reviewed does not mean it is sound. Quoting Michael Eisen, ‘the biggest threat to the proper public understanding of science is not preprints – it’s the lie we tell the public (and ourselves) that journal peer review works to separate valid and invalid science.’
Lovell-Badge then listed numerous well-known benefits of preprints, contrasting it with journal publication. For example, data and methods can be accessed much earlier when preprinted, and these are usually of high quality; he reasoned that since the work can be evaluated by the whole community, authors often take extra care to make sure what they post is valid. He suggested the rise of preprints gives us a good opportunity to create a new system that more rapidly, effectively and fairly engages the scientific community to assess the validity, audience and impact of published works. In such a system, it is also possible to review papers at any point, thereby contributing to an evolving understanding of the value and impact of the work. In contrast to the two speakers before him, he did think that journalists have a major responsibility in how science news is reported in the mass media.
The final speaker of the evening was Teresa Rayon, postdoctoral researcher at the Francis Crick Institute and member of the team of early-career researchers atpreLights. She started her talk with a reminder that in our digital age, there are plenty of ways to communicate research transparently and get the society engaged with science (e.g. through blogging, social media). Recent data about the first five years of bioRxiv (also discussedhere) highlights potential indicators (e.g. number of downloads) of preprint quality and impact, which could help journalists eager to report on preprints. She then introducedpreLights, a community platform where early-career scientists highlight preprints they feel are important; taking the audience through herfirst preLights post as an example, she stressed the value of expert yet accessible opinion on a piece of work, and of open correspondence with preprint authors. Gratifyingly, the authors acknowledged the discussion prompted by her preLights post in theopen peer review report associated with the final published paper. Rayon went on to illustrate the preLighter community’s commitment to preprints and open science by summarizing the important points from their commentary on whypreprints promote transparency and communication, rather than distortion and confusion. Finally, she proposed that initiatives like preLights can help science reporting by highlighting work to scientists, journals and journalists (without the use of jargon), having a community of experts who can give their opinion (similar to the community of experts at the Science Media Centre), and giving a voice to the new generation of researchers, who are eager to improve communication with journalists.
Teresa Rayon, postdoctoral researcher and preLighter
The prolonged, animated, and ultimately inconclusive discussion that followed these presentations highlighted just how essential it is to initiate and encourage conversations that bring together journalists, press officers, scientists and activists. There appeared to be a reasonably broad consensus that, pending further changes in the science publishing landscape, it might be necessary to have a self-imposed moratorium on mainstream reporting on preprints, giving the work time to accrue established modes of peer-review and community approval before its wider dissemination.
Given the tight deadlines of science reporting and the pressures of the newsroom, in the longer term it will be incumbent on advocates of preprints and publishing reform to familiarise journalists and press officers with the broader ecosystem around preprints. Ultimately, we believe that open community curation and peer review can provide a treasure trove of information that will complement and enrich the traditional reporting model consisting largely of a stamp of approval provided by 2-3 peer reviewers and journal editors.
Curious about the discussion? Take a look at #ORLFeb19 on Twitter!
We thank Teresa Rayon and Frank Norman for feedback on the post
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