An opportunity is available for a Postdoctoral position in the Cox Lab at the Peter MacCallum Cancer Centre in Melbourne, Australia. The position requires a highly motivated and enthusiastic postdoctoral scientist to investigate how metabolic reprogramming contributes to liver regeneration and cancer using zebrafish (Danio rerio) as a model organism. The successful candidate should hold a PhD in biochemistry, molecular biology, developmental biology or a related discipline. The person will be expected to conduct rigorous, valid and ethical research both independently and as part of the research team. The person will be expected to supervise undergraduate and postgraduate students, and technical staff. For more information on recent publications and projects running in the Cox laboratory refer to: https://www.petermac.org/research/labs/andrew-cox
Alexandra Joyner and Alberto Roselló-Díez tell us the story behind their recent paper in PLoS Biology1.
Today we have tried a new experiment (we cannot help it). Instead of elaborating too much on the scientific aspect of our recent paper about the control of organ growth in mammals1, we decided to tell the personal aspect of it. It’s a story about perseverance, collaboration and serendipity, and we hope it will be especially encouraging for young trainees striving to find their niche. Here we go:
Alex: One of the big mysteries in developmental biology is how the robustness of our body plans is achieved, perhaps best exemplified by the near equal lengths of our left and right limbs. Alberto started devising a new experimental approach to this fascinating question with a comprehensive review written by Cliff Tabin’s group in hand2, but there appeared to be limited investigations on which to base his work.
Alberto: Indeed! That’s how this story started. When I was finishing my PhD in Miguel Torres’s lab in Spain, Miguel had a great idea for a departmental retreat. Everyone had to think about a wild project, a particularly difficult question they would like to address if they had the resources to do it. Long story short, I presented my idea that while limb growth was mainly autonomous, perhaps the fine-tuning of limb size involved some kind of limb-limb crosstalk. My proposed approach involved complicated ways of achieving unilateral growth manipulation in a variety of vertebrate and invertebrate models, in order to study the potential recovery of symmetry. Frankly, my approaches were hardly viable, but then I got a suggestion from a brilliant colleague who was also doing his PhD at the time, my friend Juanma González Rosa. He suggested an elegant way of achieving unilateral manipulation: to use mouse Cre lines driven by the regulatory region of some of the known left-specific genes that operate during early development. And that was the seed of the project. We came back to our labs, and while I was writing my thesis, a review article from the great developmental biologist Lewis Wolpert revisited the topic of limb symmetry as one of the remaining mysteries in developmental biology3. This obviously bolstered my interest in the topic, and as soon as I graduated and submitted the revisions of one of our papers, I spent the following 3-4 weeks reading, formulating hypotheses and writing an experimental plan. Finding the left-specific Cre line was no easy task, because the people who had generated them were not interested in limb development, and their papers did not mention the expression in the limbs. Fortunately, they were so kind as to respond to the out-of-the-blue request of a young PhD, and even sent me pictures of staining in the limbs (thank you again, Drs Martin, Shiratori and Hamada). And that’s how I found the Pitx2-Cre driver that would be key for our studies4, and that Alex would later import from Japan even before I arrived to the lab. However, the Cre was expressed in the very early embryo, marking the left lateral late mesoderm from that stage onwards, so other genetic components were necessary to enable manipulation specifically at the critical period of limb length establishment. According to Wolpert, the problem had to be addressed at the level of the growth plate of the elongating bones, so I devised an intersectional strategy to restrict any cellular modification of interest to the growth plates of the left long bones. The new transgene I designed depended on the coincidence of two drivers, Cre and (r)tTA, to activate expression of a growth altering protein in a given cell population. The idea became to restrict expression of the protein using Pitx2-Cre and a cartilage specific rtTA in combination with the new transgene. This strategy would provide not only exquisite spatial control, but also inducibility and reversibility, as rtTA requires Doxycycline to be active.
It was March 2011 when I went back to the lab after my post-PhD reflection period. I was full of energy and determined to find a lab in which I could develop my idea. My hypothesis at the time was that the nervous system could be involved in communicating the left with the right limb, and maybe even comparing their lengths, so I ideally had to find a lab with expertise in limb and nervous system development, and the resources and experience to generate the complex genetic models the project required. I thought it would be difficult, but in a curious twist of fate, the opportunity quite literally presented itself when Alex visited our institute to present a fascinating story about nerve-released sonic hedgehog (SHH) having an important role in the fate of the stem cells of the hair bulge5. Alex had published several studies on limb development before, was an expert in nervous system development and function (especially the cerebellum), and was developing several models of recovery after organ injury, so Miguel kindly introduced me to her during their allocated meeting time.
Alex: It was unusual to have a recently graduated student on the schedule of meeting Miguel sent me, but then Alberto is an unusual scientist! After telling me about his exciting PhD limb research, Alberto proceeded to tell me about what he wanted to do for his postdoctoral research. Loving a genetic challenging in mice, I was very taken by the elegant approach Alberto had come up with to study one of the most basic and fascinating questions in development – how symmetry is attained. He visited our lab at MSKCC in New York soon after, and there was unanimous excitement to have Alberto join our group and start a new area of research.
Alberto: The excitement was reciprocal! I chose to join the lab because I perceived an atmosphere of constructive feedback and criticism during my interview, and that’s exactly what I needed for this type of project that ventured in uncharted waters. But, to be honest, things were everything but easy when I moved to New York in June 2012. First, generating the mouse lines would be quite resource demanding, so we had to choose our experiments carefully. Second, one of my experiments was more complicated than expected. I decided to try to characterise with high precision the left-right limb asymmetry at several stages of mouse development while I was building the transgene constructs, and also correlate it with the presence or absence of innervation near the growth plate, and determine how it was affected after pharmacological manipulation of candidate neurotransmitter response pathways. The precision required made the process extremely painstaking, and the results of the pharmacological manipulation were inconclusive, so when the first mice of my intersectional model were available, roughly a year after I started in Alex’s lab, we decided I would fully dedicate my time to characterise the brand-new mice. A third challenge then arose, the double-conditional allele (which I eagerly called Dragon, standing for Dox-controlled and Recombinase-Activated Gene-OverexpressiON) was unexpectedly not active in most of the cells that were supposed to express the transgene, seemingly pushing us back to square 1.
Alex:Yes, the first year was quite difficult for us but proved to me that Alberto had the resourcefulness to make the project work. Fortunately, in another twist of fate, I got in contact with Dr. Hongkui Zeng whom I had met at the Allen Institute and learned that the Tet-responsive element becomes easily inactivated in the locus we used, but that she had identified an intergenic region after extensive screening that supports (r)tTA-driven gene expression6. She had named the locus TIGhtly-REgulated or Tigre, the Spanish word for tiger (quite fitting, as Alberto is from Spain). Intriguingly, Dr. Zeng’s group was also working on a Cre- and (r)tTA-dependent intersectional gain-of-function strategy7, so we teamed up with them to modify their system and adapt it to our needs, and they generously offered to perform the embryonic stem cell manipulations.
Alberto:Yes, we quite literally found the crouching Tiger for our hidden Dragon! This collaboration was undoubtedly key to finishing the project in a timely manner, but would still require half a year to make the mice. Therefore, while our Tigre-Dragon mice were being generated, we also developed a fast way of using Pitx2-Cre to induce unilateral cell death in the limb, with which we found that the tissues surrounding the long bones can modulate bone growth8. This result made us wonder if there was communication between other tissues and the bones, and if it could work in the opposite direction. Spoiler alert: it does!
Alex, Alberto and their Tigre-Dragon mice. With a bit of help from left and right, we developed a model of unilateral cell arrest in the growing bones. Blue cells express the cell cycle suppressor p21, and brown cells express tdTomato.
Alex:That’s right! When Alberto was finally able to analyse our Tigre-Dragon mice, we were surprised to see that the mice did not show any obvious asymmetry despite having more than 50% of their chondrocytes arrested in the left hindlimb. Long story short, we found that two compensatory mechanisms accounted for symmetry maintenance: local hyper-proliferation of the undamaged cells, almost perfectly tuned to make up for the arrested cells, and more surprisingly, a systemic growth reduction that affected all limbs and the whole embryo in general. Although the systemic effect was subtle, we were quite excited about it, because to our knowledge it was the first time that this phenomenon was shown in an organism other than developing insects.
Adaptive growth by local and systemic mechanisms. Adapted from1
Alberto:Yes, that was a very positive surprise. I feel lucky that we discovered new fundamental mechanisms of growth regulation right when I was going to start my own lab. We would have liked to uncover more about the molecular mechanisms underlying our observations (and so did the reviewers), but to be fair that took over 30 years in Drosophila, so I guess it will be a long and difficult quest!
Alex:Alberto is starting the next stage of his career as an independent investigator with a wealth of interesting results and transgenic mice as a strong foundation for a lifetime’s worth of exciting projects for his lab. His perseverance has paid off in spades, along with his careful evaluation of every experimental design and result, an openness to collaborate, a thirst for charting new ground and of course a little bit of luck.
Alberto: Don’t forget the mentor that kept me on track!
Welcome to our monthly trawl for developmental biology (and other related/just plain cool) preprints.
In one of the most contentious (at least on Twitter!) pieces of preprint news in July, Tom Sheldon, Senior Press Manager at the Science Media Centerin London, voiced his concerns about the impact of preprints on public understanding of science in his ‘World View’ in Nature. Sheldon, building on an earlier SMC blog post, pictured the harm that could be done if bad science were to be deposited on preprint servers and picked up by journalists, and wondered how rigorous science would fare in a journalistic ecosystem which prioritises breaking the story first (i.e. giving credence to the preprint, not the peer reviewed article). Here’s a completely unscientific selection of the mainly negative Twitter responses to the piece, from Michael Eisen(who in fact has 3 preprints in this month’s haul!), James Fraser, Leslie Vosshall and Alejandro Sanchez Alvarado. The arguments swirled around the legitimacy of peer review, the responsibility of journalists to vet their stories properly, and the responsibility of scientists and university press offices not to oversell their results.
Away from the tumult, there was so much beautiful research deposited as preprints in July, from the molecular drivers of neurogenesis to the derivation of platypus pluripotent stem cells, cephalopod limb patterning to fern shoot development (and, right at the bottom, a truly humungous humdinger of a fungus!).
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:
Selective auxin agonists induce specific AUX/IAA protein degradation to modulate plant development
Thomas Vain, Sara Raggi, Noel Ferro, Deepak Kumar Barange, Martin Kieffer, Qian Ma, Siamsa Melina Doyle, Mattias Thelander, Barbora Pařízková, Ondřej Novák, Alexandre Ismail, Per Anders Enquist, Adeline Rigal, Małgorzata Łangowska, Sigurd Ramans Harborough, Yi Zhang, Karin Ljung, Judy Callis, Fredrik Almqvist, Stefan Kepinski, Mark Estelle, Laurens Pauwels, Stéphanie Robert
CrLFY1 promoter expression in fern tissues, from Langdale, et al.’s preprint
Nashwa Araby, Soha Soliman, Eman Abdel Raheem, Yasser Ahmed
Radial F-actin Organization During Early Neuronal Development
Durga Praveen Meka, Robin Scharrenberg, Bing Zhao, Theresa Koenig, Irina Schaefer, Birgit Schwanke, Oliver Kobler, Sergei Klykov, Melanie Richter, Dennis Eggert, Sabine Windhorst, Carlos G. Dotti, Michael R. Kreutz, Marina Mikhaylova, Froylan Calderon de Anda
The Nucleome of Developing Murine Rod Photoreceptors
Issam Al Diri, Marc Valentine, Beisi Xu, Daniel Putnam, Lyra Griffiths, Marybeth Lupo, Jackie Norrie, Jiakun Zhang, Dianna Johnson, John Easton, Abbas Shirinifard, Ying Shao, Victoria Honnell, Sharon Frase, Shondra Miller, Valerie Stewart, Xiang Chen, Michael Dyer
Role of Cnot6l in maternal mRNA turnover
Filip Horvat, Helena Fulka, Radek Jankele, Radek Malik, Jun Ma, Katerina Solcova, Radislav Sedlacek, Kristian Vlahovicek, Richard M Schultz, Petr Svoboda
Signalling pathways drive heterogeneity of ground state pluripotency
Kirsten R McEwen, Sarah Linnett, Harry G Leitch, Prashant Srivastava, Lara Al-Zouabi, Tien-Chi Huang, Maxime Rotival, Alex Sardini, Thalia E Chan, Sarah Filippi, Michael Stumpf, Enrico Petretto, Petra Hajkova
Human intestinal organoids in Capeling, et al.’s preprint
Towards an autologous iPSC-derived patient-on-a-chip
Anja Patricia Ramme, Leopold Koenig, Tobias Hasenberg, Christine Schwenk, Corinna Magauer, Daniel Faust, Alexandra K. Lorenz, Anna-Catharina Krebs, Christopher Drewell, Kerstin Schirrmann, Alexandra Vladetic, Grace-Chiaen Lin, Stephan Pabinger, Winfried Neuhaus, Frederic Bois, Roland Lauster, Uwe Marx, Eva-Maria Dehne
Need for high-resolution Genetic Analysis in iPSC: Results and Lessons from the ForIPS Consortium
Bernt Popp, Mandy Krumbiegel, Janina Grosch, Annika Sommer, Steffen Uebe, Zacharias Kohl, Sonja Ploetz, Michaela Farrell, Udo Trautmann, Cornelia Kraus, Arif B Ekici, Reza Asadollahi, Martin Regensburger, Katharina Guenther, Anita Rauch, Frank Edenhofer, Juergen Winkler, Beate Winner, Andre Reis
Differentiating hIPSCs from Burke, et al.’s preprint
Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs
Emily E Burke, Joshua G Chenoweth, Joo Heon Shin, Leonardo Collado-Torres, Suel Kee Kim, Nicola Micali, Yanhong Wang, Richard E Straub, Daniel J Hoeppner, Huei-Ying Chen, Alana Lescure, Kamel Shibbani, Gregory R Hamersky, BaDoi N Phan, William S Ulrich, Cristian Valencia, Amritha Jaishankar, Amanda J Price, Anandita Rajpurohit, Stephen A Semick, Roland Bürli, James C Barrow, Daniel J Hiler, Stephanie Cerceo Page, Keri Martinowich, Thomas M Hyde, Joel E Kleinman, Karen F Berman, José A Apud, Alan J Cross, Nick J Brandon, Daniel R Weinberger, Brady J Maher, Ronald DG McKay, Andrew E Jaffe
Sexual Dichromatism Drives Diversification Within a Major Radiation of African Amphibians
Daniel M Portik, Rayna C Bell, David C Blackburn, Aaron M Bauer, Christopher D Barratt, William R Branch, Marius Burger, Alan Channing, Timothy J Colston, Werner Conradie, J. Maximillian Dehling, Robert C Drewes, Raffael Ernst, Eli Greenbaum, Václav Gvoždík, James Harvey, Annika Hillers, Mareike Hirschfeld, Gregory Jongsma, Jos Kielgast, Marcel T Kouete, Lucinda P Lawson, Adam D Leaché, Simon P Loader, Stefan Lötters, Arie van der Meijden, Michele Menegon, Susanne Müller, Zoltán T Nagy, Caleb Ofori-Boateng, Annemarie Ohler, Theodore J Papenfuss, Daniela Rößler, Ulrich Sinsch, Mark-Oliver Rödel, Michael Veith, Jens Vindum, Ange-Ghislain Zassi-Boulou, Jimmy A McGuire
The Clytia life cycle, from Leclère, et al.’s preprint
The genome of the jellyfish Clytia hemisphaerica and the evolution of the cnidarian life-cycle
Lucas Leclère, Coralie Horin, Sandra Chevalier, Pascal Lapébie, Philippe Dru, Sophie Peron, Muriel Jager, Thomas Condamine, Karen Pottin, Séverine Romano, Julia Steger, Chiara Sinigaglia, Carine Barreau, Gonzalo Quiroga-Artigas, Antonella Ruggiero, Cécile Fourrage, Johanna Kraus, Julie Poulain, Jean-Marc Aury, Patrick Wincker, Eric Quéinnec, Ulrich Technau, Michaël Manuel, Tsuyoshi Momose, Evelyn Houliston, Richard Copley
Cortical Column and Whole Brain Imaging of Neural Circuits with Molecular Contrast and Nanoscale Resolution
Ruixuan Gao, Shoh M Asano, Srigokul Upadhyayula, Igor Pisarev, Daniel E Milkie, Tsung-Li Liu, Ved Singh, Austin Graves, Grace H Huynh, Yongxin Zhao, John Bogovic, Jennifer Colonell, Carolyn M Ott, Christopher Zugates, Susan Tappan, Alfredo Rodriguez, Kishore R Mosaliganti, Sean G Megason, Jennifer Lippincott-Schwartz, Adam Hantman, Gerald M Rubin, Tom Kirchhausen, Stephan Saalfeld, Yoshinori Aso, Edward S Boyden, Eric Betzig
Content-Aware Image Restoration: Pushing the Limits of Fluorescence Microscopy
Martin Weigert, Uwe Schmidt, Tobias Boothe, Andreas Müller, Alexandr Dibrov, Akanksha Jain, Benjamin Wilhelm, Deborah Schmidt, Coleman Broaddus, Siân Culley, Maurício Rocha-Martins, Fabián Segovia-Miranda, Caren Norden, Ricardo Henriques, Marino Zerial, Michele Solimena, Jochen Rink, Pavel Tomancak, Loic Royer, Florian Jug, Eugene W. Myers
Unsupervised correction of gene-independent cell responses to CRISPR-Cas9 targeting
Francesco Iorio, Fiona M Behan, Emanuel Goncalves, Shriram Bhosle, Elisabeth Chen, Rebecca Shepherd, Charlotte Beaver, Rizwan Ansari, Rachel Pooley, Piers Wilkinson, Sarah Harper, Adam P Butler, Euan Stronach, Julio Saez-Rodriguez, Kosuke Yusa, Mathew J Garnett
Trafimow D, Amrhein V, Areshenkoff CN, Barrera-Causil C, Beh EJ, Bilgiç Y, Bono R, Bradley MT, Briggs WM, Cepeda-Freyre HA, Chaigneau SE, Ciocca DR, Carlos Correa J, Cousineau D, de Boer MR, Dhar SS, Dolgov I, Gómez-Benito J, Grendar M, Grice J, Guerrero-Gimenez ME, Gutiérrez A, Huedo-Medina TB, Jaffe K, Janyan A, Karimnezhad A, Korner-Nievergelt F, Kosugi K, Lachmair M, Ledesma R, Limongi R, Liuzza MT, Lombardo R, Marks M, Meinlschmidt G, Nalborczyk L, Nguyen HT, Ospina R, Perezgonzalez JD, Pfister R, Rahona JJ, Rodríguez-Medina DA, Romão X, Ruiz-Fernández S, Suarez I, Tegethoff M, Tejo M, van de Schoot R, Vankov I, Velasco-Forero S, Wang T, Yamada Y, Zoppino FC, Marmolejo-Ramos F
laure Bally-Cuif & Claude Desplan, conference organizers
Invited speakers:
Geneviève Almouzni Alexander Aulehla Allison Bardin Dominique Bergmann Florence Besse Sarah Bray Claire Chazaud Enrico Coen Michèle Crozatier Alain Goriely Thomas Gregor Laura Johnston Frank Jülicher Ryoichiro Kageyama Bill Keyes Thomas Lecuit Andrew Oates Patrick O’Farrell Ewa Paluch Nancy Papalopulu Catherine Rabouille Jody Rosenblatt François Schweisguth Benjamin Simons Claudio Stern Julien Vermot Jean-Paul Vincent Magdalena Zernicka-Goetz
A perspective on our recent paper ‘CLAVATA was a genetic novelty for the morphological innovation of 3D growth in land plants’1.
In the 1950’s, the German botanist Walter Zimmermann (photo here) hypothesized a series of developmental transitions enabling plant forms to radiate during evolution2. Zimmermann’s so-called Telome Theory has received much attention from those interested in leaf evolution as it incorporates suggested steps by which early leafless plants such as Cooksonia were modified by processes of overtopping, webbing and planation to form shoots with leaves2. Less attention has been given to his ideas about earlier steps in plant evolution, namely how cell division planes translate directly into plant form in aquatic algal relatives of land plants, and how a capacity to rotate stem cell divisions through multiple planes was a key innovation of land plants, enabling them to orient growth along multiple axes2.
In mosses, a developmental transition recapitulates Zimmermann’s evolutionary transition when a shoot with multiple growth axes (3D growth) initiates from a filamentous precursor tissue (2D growth) that resembles some algal relatives of land plants. During my post-doctoral work, I collaborated with Dr Adrienne Roeder and Professor Elliot Meyerowitz at Caltech to characterize this 2D to 3D growth transition by confocal live-imaging, and showed how cell division planes start to flip around to establish an apical stem cell with tetrahedral shape during shoot initiation3. We found that new shoots and filaments can initiate right next to each other from a parent cell and concluded that local cues and asymmetric divisions were important in shoot initiation2.
When my first PhD student (Dr Chris Whitewoods, né Mr Chris White) joined my lab in Cambridge to work on moss CLAVATA function, we did not know that CLAVATA would act locally to pattern asymmetric divisions in moss shoots, but this is what we found.
CLAVATA signaling involves the production and perception of small mobile peptides, and these two functions are spatially separated1,4. Mr Joe Cammarata joined my lab and subsequently moved to Cornell to work with Prof. Mike Scanlon and Assoc. Prof. Adrienne Roeder, and we showed that disruption of either function results in problems with cell division plane orientation as shoots initiate. We also discovered that CLAVATA genes are only present in land plants, leading us to conclude that these genes contributed to a key, land plant specific innovation during evolution1.
Moving forwards, I would really like to build on our work to find out how CLAVATA specifies cell division plane orientation during moss shoot initiation, and whether CLAVATA contributed to the origin of indefinitely proliferative shoot growth in vascular plants. Answers to these questions will give fundamental new insights into plant developmental patterning and plants’ conquest of land respectively5,6.
Whilst Zimmermann’s Telome Theory ideas have been critiqued (e.g.7), phylogenetic and molecular genetic advances in a range of plant model systems mean that they are now open to experimental interrogation. I am excited about the possibility of further research to test his ideas and think that our investigation of moss CLAVATA function illustrates one way to do this.
Further reading:
1 Whitewoods et al. (2018). CLAVATA Was a Genetic Novelty for the Morphological Innovation of 3D Growth in Land Plants. Current Biology, here.
2 Zimmermann (1952). Main results of the ‘Telome Theory’. The Palaeobotanist1, here.
3 Harrison et al. (2009). Local cues and asymmetric cell divisions underpin body plan transitions in the moss Physcomitrella patens. Current Biology19, here.
4 Bowman and Eshed (2000). Formation and maintenance of the shoot apical meristem. Trends Plant Sci5, here.
5 Harrison (2017). Development and genetics in the evolution of land plant body plans. Phil. Trans. R. Soc. B372, here.
6 Harrison and Morris (2018). The origin and early evolution of vascular plant shoots and leaves. Phil. Trans. R. Soc. B373, here.
7 Beerling and Fleming (2007). Zimmermann’s telome theory of megaphyll leaf evolution: a molecular and cellular critique. Current Opinion in Plant Biology10, here.
A postdoctoral position is immediately available or on the date upon mutual agreement in the laboratory of Jianlong Wang, Ph.D., Department of Cell, Developmental and Regenerative Biology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029. The position is funded for the study of biochemical basis and regulatory circuitry for totipotent and pluripotent stem cells in the mouse and human, focusing on transcriptional, post-transcriptional and epigenetic mechanisms. Our studies utilize both in vivo mouse and in vitro cell culture models (please refer to our lab research profile here http://www.stemcellwanglab.com). Applicants should have a Ph.D. and/or an M.D. degree and have experience in mouse/human ES cell culture and/or other mammalian cell cultures including cancer cell lines. Prior experience working with laboratory mice, protein biochemistry, and cancer and stem cell biology is beneficial. Knowledge and practical skills on basic bioinformatics such as RNA-seq, ChIP-seq and CLIP-seq data analyses will be a plus.
Our group is part of the Black Family Stem Cell Institute, the MINDICH Child Health Institute and the Tisch Cancer Institute. This highly productive and collaborative environment will provide excellent resources, mentorship and support. The position offers competitive salary, guaranteed subsidized postdoc-housing and exposure to a rich environment at Icahn School of Medicine at Mount Sinai and the New York City/Manhattan area. Interested candidates should send a Cover Letter together with CV and names/contact information of 3 potential references to Jianlong Wang, Ph.D. (jianlong.wang@mssm.edu).
We are still looking for a Scientific Reviews Editor for the journal Development – for full details, please see the job advert here.
You may have noticed that this is not the first time we’ve posted this job. While we would ideally be hoping to recruit someone with some previous editorial experience, we don’t want to put off other candidates; in fact, most Reviews Editors at The Company of Biologists join us straight from the lab, with no direct experience. This is a fantastic opportunity for a developmental biologist (or someone working in a related field) who does not want to continue in the lab, but would like to stay close to the cutting edge of science, and the scientific community – and we are keen to recruit as soon as possible.
If you are interested in this position, please don’t hesitate to get in touch with me (Katherine Brown, the journal’s Executive Editor) if you want an informal chat before applying formally. And if you have any queries about potential eligibility, please get in touch with our HR department.
The great and the good of British developmental biology were in attendance, including many BSDB past-presidents and committee members, and, presumably inspired by this historical ambience, the organisers decided to set up a family tree in the atrium. Attendees would put their own names on the board, then those of their PhD and postdoctoral advisers, and link them with string. These details were also taken down on paper.
It started off relatively clean and tidy…
…but as more and more attendees added their details it turned into quite a dense network…
…and by the end of the conference there were hundreds of nodes and edges. The question then came up of what we were going to do with it.
To the delight of the organisers we decided to take the thing back with us to our office in Cambridge. It just about made it into the boot of the car…
…but some the edges and nodes of the network did not prove robust enough to survive the transit in tact (luckily we had the back up sign up sheets).
So now it needed digitising. I first just entered the data into Excel – it ended up with 349 connections from individuals to their advisers. There were almost certainly errors in transcription from scribbled handwriting to computer screen but I think I got most connections right.
But the visualisation was less easy to figure out. We could have tried something like Neurotree – The Neuroscience Academic Family Tree, but this didn’t really fit with the network created in Warwick. During my postdoc I had played around with Cytoscapeto visualise protein protein interaction data and this seemed like a better way forward. But I figured though the best thing would be an online tool where no one has to download anything, and stumbled upon Cell Maps – Systems Biology Visualisation.
This site pretty much does what I wanted. You end up with a network that looks like this
And in close up…
The arrows point to the advisers (hence Jim Smith pointing to Lewis Wolpert and Jonathan Slack, and being pointed at in turn by his students and postdocs!).
It can be quite fun to follow connections – linking Angelo Nieto to Rosa Beddington, for instance.
How to view the network
You can view and play around with the network yourself – first download this file
And go to http://cellmaps.babelomics.org/, select ‘Open Session’, and load up the file. There’s a search bar – use all caps, full name. And you can also play around with some wacky network layouts (though I think the ‘Force Directed – Default’ setting works the best!).
Any ideas?
There are some issues with this site – I keep on getting errors when trying to export the network as an image, for instance. It’s also not linked with the data itself (I had to turn the Excel into a txt file). So if anyone has other ideas about how to visualise a network of scientific connections, please comment below! Of particularly interest would be ways of visualising extra bits of information in the network (e.g. model organism, nationality, where or when one got their PhD, etc). I really have little idea what I’m doing…
Community curation needed!
One other issue is the data itself, which is clearly incomplete (just look at the single connections of luminaries like Phil Ingham and Angela Nieto!).
So we need further community curation! I’ve put the data from the sign up sheets into a Google Sheets doc. Sheet 1 has ‘raw’ data – the person in question and all of their advisers. Sheet 2 has each interaction, one after the other, which is used as the input into Cell Maps.
You can access the sheet here– and if you were at the meeting but didn’t manage to add to the physical network, I’d appreciate your input!
We’re initially planning to stick just to BSDB attendees, but there’s no reason why we can’t expand this to the global family of developmental biologists. I’d love to know your thoughts on how best to carry this family network forward.
Parasitic plants are fascinating and agriculturally relevant organisms that rely for their success on the haustorium, a specialised root structure that invades host root vasculature to derive nutrients and water. A recent paper in Development addresses the developmental origins of these crucial structures in the facultative root parasite Phtheirospermum japonicum. We caught up with first author Takanori Wakatake and his supervisor Ken Shirasu, Group Director at the RIKEN Center for Sustainable Resource Science in Yokohama, to find out more about the story.
Takanori and Ken
Ken, can you give us your scientific biography and the questions your lab is trying to answer?
KS After I got a bachelor’s degree in agricultural chemistry at the University of Tokyo, I moved to University of California, Davis, where I got a PhD degree in Genetics. My PhD thesis was on how a parasitic bacterial pathogen transfers its DNA to the host plant. As a Postdoc at the Salk Institute, I studied how plant immune signals are potentiated. Then I moved to The Sainsbury Laboratory, UK, where I continued to work on plant immunity identifying signalling components. After nearly 18 years of study abroad, I went back to Japan to open a new lab at RIKEN where I started working on parasitic plants. The main theme of our lab is to understand how plants defend themselves against pathogens and how pathogens overcome it. We work on various pathogens including bacteria, fungi, nematodes and parasitic plants, but often realize that they use similar strategies to manipulate host plants.
Takanori, how did you come to join the Shirasu lab?
TW After I made a decision to study plant science at the graduate school of the University of Tokyo, I was thinking which laboratory I should join. There were two main reasons why I chose Ken’s lab. 1) It is in RIKEN, outside the University of Tokyo. I believed that changing environments would help me to build my identity as a scientist. 2) The term “immunity” sounded cool to me because I was interested in pharmacology when I was an undergrad. I eventually became interested in arms race between plants and pathogen. What Ken suggested to me during the first interview, however, was to study parasitic plants, as pathogens. I decided to work on parasitic plants, because I wanted to do something unique.
Developmental stages of haustorium formation (Pj, P. japonicum root; At, A. thaliana root), from Figure 1 in the paper.
As far as I can tell, your paper is the first Development has ever published on the development of parasitic plants! What fascinates you about these organisms?
KW & KS How exciting! Parasitic plants are the plants that have evolved to attack own kinds. They do not infect own roots nor members of the same family. Thus, they are able to perceive host plants, which are very similar to themselves, as non-self. How they can differentiate own species from others? And, for infection, they invented a new organ called haustorium, which provides a totally new function. How did plants do that? Haustorium was independently evolved at least 12 times so it should not be so difficult. They must have modified a common machinery so following developmental stages of haustorium we may find some clues.
Time-lapse observation of nuclear behavior during early haustorium development, and with nuclei tracked. From movies 1 and 2 from the paper
Can you give us the key results of the paper in a paragraph?
KW & KS In the paper, we demonstrate that cells in the various layers of the root tissues are reprogrammed and collectively establish a new organ upon host perception. In particular, epidermal cells differentiate into specialized cells to penetrate host tissues. Other various cell types differentiate into vascular meristem-like cells to pave the way to connect parasite vascular and host vascular system for nutrient transfer. This is quite different from known developmental processes such as lateral root and nodule formation. This work also represents a high plasticity of plant roots.
Have you got any ideas about the pathways by which the inductive signals control cell fate transitions in a localised manner in the parasitic root?
KW & KS We are currently working on a putative HIF receptor we identified. We aim to elucidate the signalling pathway from HIF perception to local induction of the YUC3 gene, which encodes a key auxin biosynthesis enzyme to initiate haustorium development.
Putative procambium gene expression in the haustorium, from Figure 3 in the paper
Does your work have any implications for how to combat parasitic plants in agriculture?
KW & KS Not immediately. However, once we understand how haustoria are made, we may be able to block the process. Thus, our work set the fundamental base for the future study to dissect the process.
When doing the research, did you have any particular result or eureka moment that has stuck with you?
KW My favourite experiment in the paper is the lineage tracing using the CRE-Lox system. Initially I thought, based on marker analysis, that various cell types actually change cell fate and differentiate into procambium-like cells. To demonstrate this possibility clearly, I needed a lineage tracing experiment during haustorium development. I designed the CRE-Lox system and made a number of constructs. After many trials, I finally got the result indicating that cortex layers differentiate to procambium-like cells. It was a very satisfying moment.
Tracing cell lineage in the haustorium, from Figure 5 in the paper
And what about the flipside: any moments of frustration or despair?
TW At first, I envied the researchers who work on the established model organisms. They can easily access to mutant collections, transformation lines, complete genomes, etc, but now I am fine with our situation and try to think about what we can do. I believe new technologies such as CRISPR and magnetfection will drive the research in non-model plants.
What next for you after this paper?
TW Currently, I am trying to wrap up another paper about auxin flow and xylem bridge formation in the haustorium. After that, I would like to challenge in a new research field.
And where will this work take the Shirasu lab?
KS Intrusive cells are the interface between the parasite and host. They need to deal with host immunity system and find location of host xylem. There must be many signals going by between parasites and hosts. We aim to identify those signals.
Finally, let’s move outside the lab – what do you like to do in your spare time?
TW In general, I like listening nice music, playing games, and watching football games. Recently, I am into watching films and learning cinematography. I am also studying spices for cooking.
KS I enjoy cooking at home. I think that cooking is a creative experience, which makes me excited. It’s more like planning and doing experiments, and at the same time I can feed my family! Vegetables are coming from my small vegetable garden, where I combat a lot of pathogens! So I can do some plant immunity studies there, too!
It’s hard to describe with words how my experience has been at the Marine Biological Laboratory (MBL) in Woods Hole, Massachusetts, but I’m going to give it a try…
My attendance at the 2018 Embryology course at the MBL, has been possible thanks to an award I won in my home country, during the International course on Developmental Biology, held in Quintay, Chile (a post written by the students of the course was published before https://thenode.biologists.com/tracing-the-origins-of-developmental-biology-in-latin-america/events/ ). I felt incredibly fortunate at the time to be considered to participate in this lifechanging experience at the MBL, but it wasn’t until now that I understood what it really meant.
Performing research in Chile, as well as in most Latin American countries is quite challenging, both in terms of funding, equipment availability and time (imported items take at least one or two months to arrive). We are forced to learn how to plan experiments with caution, which is in part great as we become efficient with scarce resources (but also terrible because it limits our scientific creativity).
Here at the MBL it is the exact opposite: I can be the “crazy scientist” that I have always dreamed about, by not only repeating classical embryological experiments in all sort of species, but also thinking outside the box and testing new hypotheses without the fear of failure. This is one of the things that I’ve loved the most about the course.
I have been incredibly lucky to be able to work with so many different species, image them with a huge variety of microscopes (seriously, so many!) and yet, still had to struggle to get a slot because we were all so eager to use them. We learned how to make our own tools with Walmart items and to forge instruments with three different flames. We also had the opportunity to perform novel techniques, such as in utero CRISPR editing of mice and single molecule in situ hybridization in arthropods, among others.
Collecting samples at the MBL and field use of Foldscope with its creator Manu Prakash
And obviously, I’m aware that our lecturers are leaders in their fields from around the world. I enjoy hearing about and discussing their work first hand, as well as having the time to interact with them personally over lunch or dinner. I remember the wonderful talk that we had the privilege to witness, given by Nobel Laureate Eric Wieschaus about the biophysical properties of Drosophila development. During our famous “sweatbox” (intense Q&A), we got the opportunity to gain further insight into his mind. Someone in the audience asked how he dealt with failure, to which he smartly replied “well, failing I’m used to, so I consider myself an expert by now”, which provoked a general laughter in the room, as we all know that experimental fiascos are a common problem in our field. But he then added sage advice to that initial comment – celebrate every small success, and don’t allow every failure to discourage you.
Apart from the top scientific and intellectual level of all attendees, the people I have met are incredible, coming all from different backgrounds and cultures and I’ve learned so much from all of them. I really like the bonds that have been established amongst our group. We all contribute with our knowledge and skills, whether it was during lectures, bench work, microscope use, and even during softball practice. Of course, I’ve also enjoyed sharing a beer in our break room or at the Kidd, as well as eating in Pie in the Sky and going to the beach “collecting samples”. I have no doubt that this group will stay in touch and even collaborate in the future. I’ve been here for almost 6 weeks now and it’s been exhausting, a level of sleep deprivation that I thought I was incapable of handling at my almost 30 years old, but totally worth it.
After winning the famous softball game, with my friends Aastha and Martyna
Two days before the end of it, I’m ready to go back to the real world, but a part of me never wants this experience to end. Overall, having attended the 2018 MBL Embryology course has changed my life, and I am so glad it did. For whoever is reading this article, I encourage you to apply for the 2019 class, I promise that it will also change yours…
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