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 studentship 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
Students are expected to have chosen a laboratory for their thesis research prior to application, and to have obtained the support of the PI. A list of eligible supervisors can be found here.
Students will have access to our Discussion course during the first year, where they will:
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.
ELIGIBILITY
We welcome applications from those who hold a relevant first degree at the highest level (minimum of a UK II.i Honours Degreeor equivalent) as well as a Master’s Degree in a relevant discipline. You must have a passion for scientific research.
Wellcome provide full funding at the ‘Home/EU’ rate. Funding does not include overseas fees, so non-EU applicants will need to find alternative funding sources to cover these.
Another bumper month for developmental biology and related preprints, this time featuring spiders, lampreys, amphiouxus and plenty of zebrafish, worm and fly research. Also a big month for fans of Sox genes, which turned up in the title of five preprints! My visual highlight is the preprint from David Parichy’s group on zebrafish scale development – well worth downloading the PDF to gawp at the imaging.
The preprints were hosted on bioRxiv, PeerJ, andarXiv. Use these links to get to the section you want:
Discovery of a new path for red blood cell generation in the mouse embryo
Irina Pinheiro, Ozge Vargel Bolukbasi, Kerstin Ganter, Laura A. Sabou, Vick Key Tew, Giulia Bolasco, Maya Shvartsman, Polina V. Pavlovich, Andreas Buness, Christina Nikolakopoulou, Isabelle Bergiers, Valerie Kouskoff, Georges Lacaud, Christophe Lancrin
Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth
Andrew Cox, Allison Tsomides, Dean Yimlamai, Katie Hwang, Joel Miesfeld, Giorgio Galli, Brendan Fowl, Michael Fort, Kimberly Ma, Mark Sullivan, Aaron Hosios, Erin Snay, Min Yuan, Kristin Brown, Evan Lien, Sagar Chhangawala, Matthew Steinhauser, John Asara, Yariv Houvras, Brian Link, Matthew Vander Heiden, Fernando Camargo, Wolfram Goessling
Tracking mandibular arch cell rearrangements in Tao, et al.’s preprint
Oscillatory cortical forces promote three dimensional cell intercalations that shape the mandibular arch
Hirotaka Tao, Min Zhu, Kimberly Lau, Owen Whitley, Mohammad Samani, Xiao Xiao, Xiao Xiao Chen, Noah A. Hahn, Weifan Liu, Megan Valencia, Min Wu, Xian Wang, Kelli D. Fenelon, Clarissa C. Pasiliao, Di Hu, Jinchun Wu, Shoshana Spring, James Ferguson, Edith P. Karuana, R. Mark Henkelman, Alexander Dunn, Huaxiong Huang, Hsin-Yi Henry Ho, Radhika Atit, Sidhartha Goyal, Yu Sun, Sevan Hopyan
Tracking development of the zebrafish retina, from Matejcic, et al.’s preprint
Single-cell analysis identifies EpCAM+/CDH6+/TROP-2- cells as human liver progenitors.
Joe M Segal, Daniel J Wesche, Maria Paola Serra, Bénédicte Oulés, Deniz Kent, Soon Seng Ng, Gozde Kar, Guy Emerton, Samuel Blackford, Spyros Darmanis, Rosa Miquel, Tu Vinh, Ryo Yamamoto, Andrew Bonham, Alessandra Vigilante, Sarah Teichmann, Stephen R Quake, Hiromitsu Nakauchi, S Tamir Rashid
Randal Burns, Eric Perlman, Alex Baden, William Gray Roncal, Ben Falk, Vikram Chandrashekhar, Forrest Collman, Sharmishtaa Seshamani, Jesse Patsolic, Kunal Lillaney, Michael Kazhdan, Robert Hider Jr., Derek Pryor, Jordan Matelsky, Timothy Gion, Priya Manavalan, Brock Wester, Mark Chevillet, Eric T. Trautman, Khaled Khairy, Eric Bridgeford, Dean M. Kleissas, Daniel J. Tward, Ailey K. Crow, Matthew A. Wright, Michael I. Miller, Stephen J Smith, R. Jacob Vogelstein, Karl Deisseroth, Joshua T. Vogelstein
| Genome tools
An optimized toolkit for precision base editing
Maria Paz Zafra, Emma M Schatoff, Alyna Katti, Miguel Foronda, Marco Breinig, Anabel Y Schweitzer, Amber Simon, Teng Han, Sukanya Goswami, Emma Montgomery, Jordana Thibado, Francisco J Sanchez-Rivera, Junwei Shi, Christopher R Vakoc, Scott W Lowe, Darjus F Tschaharganeh, Lukas E Dow
Robust single-cell DNA methylome profiling with snmC-seq2
Chongyuan Luo, Angeline Rivkin, Jingtian Zhou, Justin P Sandoval, Laurie Kurihara, Jacinta Lucero, Rosa Castanon, Joseph R Nery, Antonio Pinto-Duarte, Brian Bui, Conor Fitzpatrick, Carolyn O’Connor, Seth Ruga, Marc E Van Eden, David A Davis, Deborah C Mash, M. Margarita Behrens, Joseph R Ecker
Community-driven data analysis training for biology
Bérénice Batut, Saskia Hiltemann, Andrea Bagnacani, Dannon Baker, Vivek Bhardwaj, Clemens Blank, Anthony Bretaudeau, Loraine Guéguen, Martin Čech, John Chilton, Dave Clements, Olivia Doppelt-Azeroual, Anika Erxleben, Mallory Freeberg, Simon Gladman, Youri Hoogstrate, Hans-Rudolf Hotz, Torsten Houwaart, Pratik Jagtap, Delphine Lariviere, Gildas Le Corguillé, Thomas Manke, Fabien Mareuil, Fidel Ramírez, Devon Ryan, Florian Sigloch, Nicola Soranzo, Joachim Wolff, Pavankumar Videm, Markus Wolfien, Aisanjiang Wubuli, Dilmurat Yusuf, Rolf Backofen, James Taylor, Anton Nekrutenko, Björn Grüning
Seán I O’Donoghue, Benedetta F Baldi2, Susan J Clark, Aaron E Darling, James M Hogan, Sandeep Kaur, Lena Maier-Hein, Davis J McCarthy, William J Moore, Esther Stenau, Jason R Swedlow, Jenny Vuong, James B Procter
David Trafimow, Valentin Amrhein, Corson N. Areshenkoff, Carlos Barrera-Causil, Eric J. Beh, Yusuf Bilgiç, Roser Bono, Michael T. Bradley, William M. Briggs, Héctor A. Cepeda-Freyre, Sergio E. Chaigneau, Daniel R. Ciocca, Juan Carlos Correa, Denis Cousineau, Michiel R. de Boer, Subhra Sankar Dhar, Igor Dolgov, Juana Gómez-Benito, Marian Grendar, James Grice, Martin E. Guerrero-Gimenez, Andrés Gutiérrez, Tania B. Huedo-Medina, Klaus Jaffe, Armina Janyan, Ali Karimnezhad, Fränzi Korner-Nievergelt, Koji Kosugi, Martin Lachmair, Rubén Ledesma, Roberto Limongi, Marco Tullio Liuzza, Rosaria Lombardo, Michael Marks, Gunther Meinlschmidt, Ladislas Nalborczyk, Hung T. Nguyen, Raydonal Ospina, Jose D. Perezgonzalez, Roland Pfister, Juan José Rahona, David A. Rodríguez-Medina, Xavier Romão, Susana Ruiz-Fernández, Isabel Suarez, Marion Tegethoff, Mauricio Tejo, Rens van de Schoot, Ivan Vankov, Santiago Velasco-Forero, Tonghui Wang, Yuki Yamada, Felipe C. Zoppino, Fernando Marmolejo-Ramos
Christos D Arvanitidis, Richard M Warwick, Paul J Somerfield, Christina Pavloudi, Evangelos Pafilis, Anastassis Oulas, Giorgos Chatzigeorgiou, Vasilis Gerovasileiou, Theodoros Patkos, Nicolas Bailly, Francisco Hernandez, Bart Vanhoorne, Leen Vandepitte, Ward Appeltans, Robert Adlard, Peter Adriaens, Ahn Kee-Jeong, Ahyong Shane, Akkari Nesrine, Gary Anderson, Angel Martin, Claudia Arango, Tom Artois, Stephen Atkinson, Ruud Bank, Anthony D Barber, Joao P Barbosa, Ilse Bartsch, Denise Bellan-Santini, Jimmy Bernot, Annalisa Berta, Rüdiger Bieler, Magda Błażewicz, Phil Bock, Ruth Böttger-Schnack, Philippe Bouchet, Nicole Boury-Esnault, Geoff Boxshall, Christopher B Boyko, Simone Nunes Brandão, Rod Bray, Niel L Bruce, Stephen Cairns, Tania N Campinas Bezerra, Paco Cárdenas, Benny KK Chan, Tin-Yam Chan, Lanna Cheng, Morgan Churchill, Laure Corbari, Ralf Cordeiro, Astrid Cornils, Keith A Crandall, Thomas Cribb, Jean-Loup D’hondt, Meg Daly, Mikhail Daneliya, Jean-Claude Dauvin, Peter Davie, Claude De Broyer, Valentin De Mazancourt, Nicole De Voogd, Peter Decker, Danielle Defaye, Henk Dijkstra, Martin Dohrmann, Daryl Domning, Rachel Downey, Inna Drapun, Ursula Eisendle-Flöckner, Christine Ewers-Saucedo, Marien Faber, Diego Figueroa, Julian Finn, Gustavo Fonseca, Ewan Fordyce, William Foster, Hidetaka Furuya, Horia Galea, Oscar Garcia-Alvarez, Rade Garic, Rebeca Gasca, Santiago Gaviria-Melo, Sarah Gerken, David Gibson, João Gil, Arjan Gittenberger, Chris Glasby, Serge Gofas, Samuel E Gómez-Noguera, David González-Solís, Dennis Gordon, Michal Grabowski, Cinzia Gravili, José M Guerra-García, Roberto Guidetti, Katja Guilini, Kerry A Hadfield, Ed Hendrycks, Bachiller Herrera, Ju-Shey Ho, Jens Høeg, Oleksandr Holovachov, Matthew D Hooge, John Hooper, Tammy Horton, Lauren Hughes, Matús Hyžný, Luiz IF Moretti, Tohru Iseto, Viatcheslav N Ivanenko, Gerhard Jarms, Damià Jaume, Krzysztof Jazdzewski, Ivana Karanovic, Young-Hyo Kim, Rachael King, Michelle Klautau, Jürgen Kolb, Alexey Kotov, Traudl Krapp-Schickel, Antonina Kremenetskaia, Reinhardt Kristensen, Andreas Kroh, Sven Kullander, Rafael La Perna, Sara LeCroy, Daniel Leduc, Rafael Lemaitre, Anne-Nina Lörz, Jim Lowry, Enrique Macpherson, Larry Madin, Tomasz Mamos, Renata Manconi, Bruce Marshall, David J Marshall, Patrick Martin, Sandra McInnes, Jan Mees, Tõnu Meidla, Kelly Merrin, Dmitry Miljutin, Claudia Mills, Vadim Mokievsky, Tina Molodtsova, Rich Mooi, André C Morandini, Rosana Moreira Da Rocha, Fabio Moretzsohn, Jonas Mortelmans, Jeanne Mortimer, Luigi Musco, Thomas A Neubauer, Eike Neubert, Peter NG Neuhaus, Anh D Nguyen, Claus Nielsen, Jon Norenburg, Tim O’Hara, Hisayo Okahashi, Dennis Opresko, Masayuki Osawa, Yuzo Ota, Gustav Paulay, Vincent Perrier, William Perrin, Iorgu Petrescu, Bernard Picton, John F Pilger, Andrzej Pisera, Dan Polhemus, Gary Poore, James D Reimer, Hans Reip, Michael Reuscher, Pilar Rios Lopez, Marc Rius, Klaus Rützler, Alexander Rzhavsky, José Saiz-Salinas, André F Sartori, Heinrich Schatz, Bernd Schierwater, Andreas Schmidt-Rhaesa, Simon Schneider, Christine Schönberg, André R Senna, Cristiana Serejo, Shabuddin Shaik, Shokoofeh Shamsi, Jyotsna Sharma, Noa Shenkar, Andrew Shinn, Jacek Sicinski, Volker Siegel, Petra Sierwald, Elizabeth Simmons, Frederic Sinniger, Duncan Sivell, Boris Sket, Harry Smit, Nicole Smol, Jesser F Souza-Filho, Jörg Spelda, Sérgio N Stampar, Eric Stienen, Pavel Stoev, Sabine Stöhr, Malin Strand, Eduardo Suárez-Morales, Mindi Summers, Billie J Swalla, Stefano Taiti, Masaatsu Tanaka, Anne H Tandberg, Danny Tang, Mark Tasker, Harry ten Hove, Jan J ter Poorten, Jim Thomas, Erik V Thuesen, Ben Thuy, Juan T Timi, Antonio Todaro, Xavier Turon, Peter Uetz, Sergiy Utevsky, Jean Vacelet, Risto Väinölä, Sancia ET van der Meij, Ton van Haaren, Virág Venekey, Chris Vos, Genefor Walker-Smith, Chad T Walter, Les Watling, Matthew Wayland, Christopher Whipps, Gary Williams, Robin Wilson, Moriaki Yasuhara, Joana Zanol, Wolfgang Zeidler
In January 2018, twenty-one graduate students and early career researchers from across South and North America participated in the International Course on Developmental Biology, an EMBO Practical Course held at the Marine Biology Station of Quintay-Chile (CIMARQ). This two-week course was led by eight world-renowned researchers, Drs. Roberto Mayor, Nipam Patel, John Ewer, Raymond Keller, Alejandro Sánchez-Alvarado, Kathleen Whitlock, Claudio Stern and Andrea Streit, many of whom started or currently base their careers in Latin American countries. First offered in 1999, the creation of this course reflected the enthusiasm of Latin American researchers to promote and enhance the field of Developmental Biology in this region by providing an opportunity for young scientific investigators to learn current research techniques and become familiar with model organisms used in this field. A successful outcome from the course was the creation of the Latin American Society of Developmental Biology (LASDB) in 2003, which holds biannual meetings for researchers to disseminate their findings and network with colleagues throughout Latin America. Although the changing political, social and economic climate still presents challenges for young researchers, remarkable progress has been made over the past 20 years. Notably, with several of the recent participants of this course having supervisors who also completed the course earlier in their career, the International Course on Developmental Biology is clearly an important part of the emerging research landscape.
For many centuries, Developmental Biology was thought of as a descriptive science. Naturalists dedicated themselves to describing the extensive modifications that occur during the development of various species, characterizing and defining embryo size and shape, as well as the duration of different developmental stages. They addressed fundamental questions that remain to this day: How does a single cell give rise to a complete organism? What are the molecular signals involved? To answer these questions, scientists began using organisms at different levels of complexity, establishing the classical experimental models of Developmental Biology: the roundworm, fruitfly, frog, zebrafish, chicken and mouse, or C. elegans, Drosophila, Xenopus, Danio rerio, Gallus gallus and Mus musculus, as they are affectionately known by scientists. Developmental Biology began to revolutionize in the ‘70s when new technologies such as recombinant DNA became available to study how genes specify different tissue identities. In the ‘80s, we began to talk about homeobox genes, promoters, transcription factors and enhancers, and started using gene expression techniques such as in situ hybridization. As questions at the genetic and morphogenetic level began to be clarified, other questions started to arise: How does evolution shape developmental processes? How can development be modified by the surrounding environment? How can we take advantage of the plasticity of development?
Today, Developmental Biology is a highly-regarded field of study, being a course requirement of most undergraduate programs in the biological sciences. But why did we, as young scientific investigators choose it as our research discipline? We all agree: when you first observe a developing organism under the lens of a microscope, the entire world becomes fascinating. We see life’s great questions in our work. For instance, when does a cell leave it’s past behind and enter into it’s destiny? What makes a cell unique? What are the costs of differentiation? Could it be immobility, like for osteocytes; or programmed cell death, without which the fingers would not exist; or perhaps pruning, like what more than half of the brain’s synaptic connections undergo to achieve functionality. Then there are the milestones. In one of our seminars by Prof. Roberto Mayor, we were given to ponder the famous quote by Lewis Wolpert, that it is “not birth, marriage or death, but gastrulation which is truly the most important time in your life”. With such intriguing insights into the facts of life, how could any other subject area compare?
Simply exploring your surroundings in Latin America leaves one searching for answers. With unique habitats holding nearly one-fifth of the world’s plant and vertebrate species (Myers et al., 2000), it has been called “a living laboratory” and is a place of continuous discovery. This was made evident to us, by exploring just a few meters on the coastal shore of the Quintay waters, where we observed a great diversity of organisms, protected between the rocks before being revealed under our microscope lenses. Unfortunately, human activities that trigger climate change, diseases, and species introductions are affecting natural ecosystems. So we are given the challenge to find new research models to discover unique molecular and cellular mechanisms before they are lost entirely. Several research groups such as Dr. Alejandro Sánchez-Alvarado’s lab are investigating emerging model systems which may help us to overcome types of illness and injury not possible today.
Despite the benefits of conducting Developmental Biology research in Latin America, the reality is that resources and funding are limited. Countries that have an established tradition of scientific investment such as Brazil, Argentina, Mexico and Chile (Marcellini et al., 2017) are more equipped than others; however, careful experimental design, collaboration and creative problem solving are essential. All of us came with different backgrounds: free or paid access to undergraduate studies, different levels of research experience, different levels of English fluency, among others, which showed us the challenges that everyone was going through in the road to pursuing our dream of becoming scientists. However, all of these differences were set aside during the two-week course. The appreciation of the personal value of each participant and faculty member, the willingness to help each other, the equality with which the faculty and participants exchanged ideas was indicative of the underlying message of this course: advance together as one.
As scientists who study the transient process of life as it acquires it’s form and function, we are part of a minority that has the knowledge and the opportunity to make the world a better place. With climate change, wildlife extinction, food and resource crisis at our doors, difficult times are ahead of us. It is our responsibility to observe what is going on around us, make predictions, test hypotheses, and not simply resign ourselves to the way things are. We must share our knowledge, explain science and impact our society. It is in our hands to spread scientific knowledge to the general public and especially, to future scientists at a young age. This can be achieved by creating outreach programs, such as the television series that Dr. Kate Whitlock created, La Alegría de la Ciencia, which can stimulate children and adults to be interested in Developmental Biology. Science must be inclusive and not limited to scientists. Funding reviewers and government decision makers also need to be informed about our work. Here it is our duty as Developmental Biologists to explain that our research is more than simply “basic science” with no significant contribution to solve current problems. Rather, it is through studying processes such as cell migration, epithelial-mesenchymal transition, control of gene expression, and cell death that we can solve problems in reproduction, development, disease, aging and regeneration.
The personal and professional experiences of this two-week happy confinement in Quintay are some of the most illuminating and transforming that many of us have. Although separated now in different countries and continents, we have shared unforgettable moments of life and learning in this course and the doors were left open to continue working together in the future. We go forward knowing that we CAN make a difference if only we keep pushing towards a better future.
Group photo, taken moments before getting soaked by an incoming wave. Bottom row, left to right: Emma Rangel Huerta, Angelly Vasquez, Mateus Antonio Berni, Lorena Agostini Maia, Jessica Cristina Marin Llera, Nancy María Farfán, Nipam Patel. Middle row, left to right: Lautaro Gándara, Jennifer Giffin, Maria Belen Palacios, Luiza Saad, Estefanía Sánchez-Vásquez, Jorge Antolio Domínguez-Bautista, Adrián Romero, Roberto Mayor, Raymond Keller. Top row, left to right: Fernando Faunes, John Rojas, Sandra Edwards, Elias Barriga, Lucía Bartolomeu, Eugene Tine, Soraya Villaseca, Paula M. González, Matías Preza, Maria Fernanda Palominos.
“A continent whose thriving biodiversity represents endless forms most beautiful and most wonderful that are a source of inspiration and opportunities for the Evo-Devo community” (Marcellini et al., 2017).
Written by the participants of the 2018 International Course on Developmental Biology.
References
Marcellini S, González FA, Sarrazin AF, Pabón-Mora N, Benítez M, Piñeyro-Nelson A, Rezende GL, Maldonado E, Schneider PN, Grizante MB, Da Fonseca RN, Vergara-Silva F, Suaza-Gaviria V, Zumajo-Cardona C, Zattara EE, Casasa S, Suárez-Baron H, Brown FD. (2017). Evolutionary developmental biology (Evo-Devo) research in Latin America. J. Exp. Zool. (Mol. Dev. Evol.) 328B:5-40.
Myers N, Mittermeier RA, Mittermeier CG, da Fonseca GAB, Kent J. (2000). Biodiversity hotspots for conservation priorities. Nature 403: 853-858.
As well as publishing Development and four other journals, and supporting scientists through travelling fellowships and meeting grants, The Company of Biologists also runs a successful series of Workshops.
The Workshops bring leading experts and early career scientists from a diverse range of scientific backgrounds to focus on one topic together. Topics are often interdisciplinary and cover some of the most exciting current biology, as you can see in the archive.
The Workshop Committee are currently seeking proposals for four Workshops to be held during 2020. They are particularly keen to receive proposals from postdocs for one of the Workshops.We at the Node would also encourage applicants from developmental biology to think about applying!
The Marine Biological Laboratory is seeking applicants for full-time Research Assistant and Research Associate positions with the Josephine Bay Paul Center for Comparative Molecular Biology and Evolution (http://www.mbl.edu/jbpc/).
To develop CRISPR in rotifers:
We seek a motivated, creative and innovative Research Assistant or Research Associate to join the laboratories of Kristin Gribble and David Mark Welch. Our research combines comparative genomics, biochemistry, and life history to study aging, maternal effects, and DNA damage prevention and repair using rotifers, a novel aquatic invertebrate model system for studies of aging, neurobiology, genome evolution, and ecology. The successful candidate will develop genome editing techniques in rotifers, including CRISPR/Cas9, as part of a broad initiative at the MBL to advance new aquatic and marine models for biological discovery. We invite individuals with experience in genome editing in other animals to join this expanding program.
To study the biochemistry of DNA repair in bdelloids:
We seek a Research Assistant to join the laboratory of David Mark Welch. Our research combines comparative genomics, biochemistry, and life history to study the evolution of bdelloid rotifers, extraordinarily resilient animals adapted to highly stressful environmental conditions. The successful candidate will contribute to an ongoing project to clone, express, purify, and assay a variety of rotifer proteins involved in DNA damage prevention and repair. There is considerable opportunity for motivated, self-directed individuals to participate in technique development, manuscript development and publication. Position level and salary will depend on education and experience.
We seek applicants for a full-time Research Assistant position with the Keck Sequencing Facility of the Josephine Bay Paul Center. The successful applicant will contribute to projects that will explore diversity of microbes in various communities and the influence of changing environments on microbial population structures. Responsibilities include, but are not limited to, laboratory management, preparation and massively high-throughput next-generation sequencing of marker gene and metagenomic libraries from environmental genomic DNA, and computational analysis of such datasets.
A neuroscience Postdoctoral Research Associate position is available in the Robles Lab at Purdue University (www.robleslab.com). Our laboratory applies advanced genetic and microscopic imaging techniques to understand how the nervous system develops in the larval zebrafish. We use confocal laser scanning microscopy to image the structural development of genetically targeted neurons within the intact developing brain. Our major area of emphasis is developing novel, in vivo imaging assays to examine the cellular and circuit-level abnormalities underlying complex neurological disorders such as autism and epilepsy.
Candidates should have a Ph.D. in neuroscience, cell biology, genetics, or a related field. The ideal candidate will have expertise in microscopy, image analysis, and molecular biology techniques. Special consideration will be given to applicants with expertise in developing and implementing computational strategies for data/image analysis.
Please send your CV, a cover letter stating your research interests and professional goals, and the contact information for three (3) references to:
This year, is the BSDB’s 70th anniversary, and this was clearly reflected at our Spring Meeting, 15-18 April 2018 in Warwick! Apart from an outstanding speaker list, and the award of most BSDB medals & prizes of 2018, we saw a history session which looked back at the past, to then project into the future of Developmental Biology. Other specials were a very engaging PhD and postdoc social, the weaving of pedigree networks (with little labels, pins and threads of wool), and the live presentations of DB raps composed and sung by Jerry aka Gerald H Thomsen PhD and produced and mixed by Philip Larsen. See below a few image impressions of the meeting (taken from your many tweets!) and/or listen to the two raps! A detailed meeting report will follow.
Rap 1: BSDB History (part I & II)
Rap 2: Morphogen Mix
Gerald Thomsen, Josh Brickman and Philip Larsen
Only a tiny selection of participants
Emilia receives the Beddington medal from Simon Bullock
Nick Hopwood
The panel discussion
The PhD and postdoc social
PhD and postdoc social
Gearing up for the conference dinner
Weaving pedigree networks: Eric Wieschaus, David Ish-Horowicz, Claudio Stern, Austin Smith
A Wellcome Trust funded Postdoctoral Research Associate position is available in the lab of Dr. Matt Towers at the University of Sheffield, UK, to work on vertebrate limb development. How embryonic development is timed and scaled remains enigmatic. Understanding the underlying mechanisms remains a central challenge in biology, since these mechanisms coordinate the growth and patterning of all tissues and organs, and when disrupted are likely to form the basis of many congenital disorders. Our recent work on the embryonic chick wing demonstrates a pivotal role for intrinsic timers in limb development (Chinnaiya et al, Nat Comms 2014, Saiz-Lopez et al, Nat Comms 2015; Saiz-Lopez et al, Development 2017, Pickering et al, Biorxiv 2018). The aim of this project is to use a combination of classical grafting techniques and modern genomic analyses in chick embryos to understand the molecular mechanisms of how cells measure time in vivo.
A position (#123768) is available immediately for a Postdoctoral Scholar to contribute to our multidisciplinary studies aimed at elucidating the molecular basis of chick neural crest and placode cell development. The postdoc will conduct independent research and assist in the training of students in the laboratory of Dr. Lisa Taneyhill at the University of Maryland.
Laboratory skills: Molecular biology and biochemical assays (e.g., recombinant DNA/cloning; DNA, RNA, and/or protein blotting); immunohistochemistry; and/or in situ hybridization. Experience with microscopy and spectroscopy, chick embryology (including microdissections and electroporation), and tissue culture is desirable. For more information on the lab, please see http://www.ansc.umd.edu/people/lisa-taneyhill.
Qualifications: An advanced degree (Ph.D.) in Developmental, Molecular and/or Cell Biology is required. Fluency in spoken and written English is required. Compensation: Salaries are highly competitive, negotiable and commensurate with qualifications. Fringe benefits offered. Applicants must apply through eTerp at https://ejobs.umd.edu. Applications will be accepted until a suitable candidate is identified.
Have you ever wondered how our hands and feet evolved? This question, which commonly evokes fish crawling from sea to land, has long been a subject of interest, both for palaeontologists and developmental biologists. Appendages are an important part of the tool kit of anatomical innovations that emerged in vertebrates. Limbs, wings and fins certainly contributed to the evolutionary success of the whole group, as they are a fertile substrate for all kinds of ecological adaptations. However, the evolutionary history of vertebrate appendages is complex and far from being completely understood, particularly as we go back into the past to the very origin of the vertebrate lineage. It is believed that our chordate ancestors already had median fin folds. Then, both fin rays and endoskeletal elements appeared in the median fins of the first jawless vertebrates, and were maintained in modern members of this group, such as lampreys and hagfish. Later in evolution, paired appendages emerged around 450 million years ago in the first jawed vertebrates (i.e. stem gnathostomes), and were therefore inherited by modern sharks and teleost fish. Finally, when vertebrates conquered land, paired fins evolved to limbs in tetrapods. We know very little about these different steps, particularly about the early ones (1). So, for example, the evolutionary origin of paired fins is still debated and several theories have been around for a while. Most popular hypotheses include a common origin for gills and paired fins, the emergence of the paired appendages from an ancestral lateral fin fold, and, more recently, the exaptation of their developmental program from the pre-existing median fins in jawless vertebrates.
ZRS function in teleost fish
Neil Shubin (University of Chicago), who is well-known for his participation in the discovery of the Tiktaalik roseae (2), is certainly among the scientists most captivated by the evolutionary history of vertebrate appendages. From his long interest in the topic, and through his scientific interaction with an expert in zebrafish epigenomics, José Luis Gómez-Skarmeta (CABD, Seville), stemmed a project that flourished as more people got involved. Igor Schneider (University of Pará, Brasil), a former member of Shubin’s group interested in understanding the fin to limb transition, also joined the venture. Together they focused their attention on investigating the evolutionary origin of a very famous enhancer, the sonic hedgehog (Shh) limb enhancer, ZRS* (i.e. Zone of polarizing activity Regulatory Sequence). Located one mega-base away from the gene promoter in the mouse genome, this cis-regulatory element has been described as solely responsible for directing Shh expression to the posterior limb bud. Gain-of-function point mutations in the ZRS sequence result in polydactyly in human patients; conversely, loss-of-function mutations in mice result in severe distal truncations of the extremities (3). It was known that the ZRS sequence is deeply conserved in the genome of all jawed vertebrates, so the team conducted classical transgenesis assays in mice and zebrafish to ask if the ZRS regulatory code was also functionally conserved. In parallel, they used 4C-seq to determine the 3D architecture of the locus in mice and fish, and thus to evaluate if there was conservation also at this level. All these experiments were positive, and in March 2015 Igor Schneider visited Seville to coordinate the work and discuss the results. It was during that visit that the possibility and the necessity of completing the study by generating a deletion of the ZRS element in fish were contemplated.
In principle, generating a chromosomal deletion in a well-established model organism wouldn’t seem an impossible task in the CRISPR era. However, in the zebrafish genome, as in all other ostariophysan fish (including ≈7900 teleost species), the shh locus was duplicated after the teleost-specific whole genome duplication event. The presence of the paralogs shha and shhb was in this case experimentally very challenging. After some discussion involving some reference literature (3) and logistics, Igor and José simply walked the 5 metres between José Luis’ office and mine. In contrast to ostariophysans, the second shh paralog was specifically lost in the percomorph lineage during evolution, restoring the genomic complexity to a single gene and a single ZRS element. Percomorpha is the largest group of vertebrates, including almost 16000 living species (i.e. one in every four vertebrates), among them the Japanese rice fish known as medaka (Oryzias latipes). Despite its numerous experimental advantages and the increasing size of the community in the last years, still there are not that many groups working with medaka as a genetic tool outside Japan. Luckily, ours is one of them.
More regulatory complexity than anticipated
Joaquín Letelier, a Chilean postdoctoral researcher in my laboratory, immediately set up the CRISPR-Cas9 experiments necessary to ablate a 400 bp region of the ZRS in medaka. Before the end of 2015 we had the first clear and yet disappointing results. In contrast to the situation in mouse, the deletion of the enhancer in medaka was not sufficient to eliminate shh expression in the pectoral fin buds. Although reduced to 50%, the gene was still expressed in the fin primordia, and consequently, the bone architecture of the mature fin was only mildly affected in the ZRS mutant fish. At that point, I must confess, I was very close to dropping the project. However, José Luis and Joaquín never surrendered. They argued that the chromosomal deletion was perhaps too narrow (i.e. it was initially designed to delete specifically critical ETS sites), and convinced me to keep on with a second CRISPR-Cas9 round, this time deleting the entire conserved ZRS region of approximately 950 bp. Months later, my fears were confirmed when the second deletion resulted in an almost identical phenotype. Again a disappointing 50% reduction of sonic expression and very mild endoskeletal defects in adult fins. How was this possible? The simplest explanation may come from the existence of alternative enhancers controlling shh expression in the fin buds. Even when a single ZRS enhancer had been described in mice, for many other genes there was growing evidence for the existence of totally or partially redundant enhancers, also known as shadow enhancers (4): a pervasive theme in living organisms that ensures transcriptional robustness. We then used all information on epigenetic marks that we could gather from published resources, as well as from our own data in medaka and zebrafish, to identify promising regions in the shh locus that may act as alternative enhancers. Several elements were tested in transgenesis assays and we were lucky to identify a region located a few kilobases away from ZRS, both in the fish and human genomes, that was indeed able to drive reporter expression in the developing pectoral fins. The expression pattern confined to the posterior region of the bud was very similar if not identical to ZRS. We named this region as shadow ZRS (sZRS). This was by itself a very important observation showing that the simple regulatory logic observed in mice was not the general rule, and that additional enhancers played a role in different vertebrate species.
Hot news from the medaka front
The discovery of the new shadow enhancer kind of satisfied our scientific ambitions, and Igor took over the responsibility of assembling a preliminary draft with all the data. On the 26th of October of 2016, precisely the day after Igor delivered that first draft, Joaquín stormed into my office to show me fascinating pictures taken with his mobile phone a few minutes before. The images (see Figure 1) showed that the adult 950 bp-deleted fish did not have dorsal fins! It was too good to be true. Since we immediately understood the deep evolutionary implications of the finding, Joaquín rushed to confirm the genotype of all the fish without dorsal fins found in the tank. Out of all animals genotyped, all the finless fish were homozygous for the deletion. I could not believe it! At that time José Luis was abroad in Australia for a short sabbatical, and Neil was participating in an Antarctic expedition. Despite the different time zones, everybody replied immediately to a mail with the subject: hot news from the medaka front.
But, why were we all so excited? Well, the finding provided conclusive support for a shared regulatory logic controlling the development of paired (i.e pectoral) and unpaired (i.e. dorsal) appendages. This was indicating a common evolutionary origin for both types of appendages in stem gnathostomes. Since dorsal fins appear first in the fossil records, the discovery pointed to paired fins emergence by the exaptation of a developmental program first established in the median fins. The hypothesis had been formulated years before (5, 6), but this was a direct genetic demonstration entailing the functional conservation of a critical enhancer for more than 450 million years.
Finally, the finless fish
In the following months everybody did their best to complete the detailed analysis of the mutant phenotype and the ZRS expression in the different fins. In March 2017 we were ready to submit the paper, all believing the data deserved the best visibility. Happily, Tiago Faial, a senior editor in Nature Genetics, also saw the potential of the work and decided to send it for review. The review process was long but certainly improved substantially the quality of the paper. Although the reviewers found the work interesting, they requested us to delete also the shadow enhancer sZRS. They reasoned that if both ZRS and sZRS control shh expression in the pectoral fin bud, as our experiments suggested, their simultaneous deletion should result in a stronger phenotype. Again, Joaquín took the control and generated, in a record time, a larger deletion of 3.4 Kb encompassing both enhancers. There are many reasons for which such experiment would not yield the expected results. Among other things, additional unidentified enhancers may play a redundant role in paired fins. As a “defensive” experiment, we started another round of transgenics, but no additional fin enhancers were found. Then, to my absolute relief and delight, the results of the larger deletion came out. In the absence of ZRS and sZRS, shh failed to be expressed in the developing pectoral and pelvic fins, thus causing a very severe truncation of these extremities. Without paired and dorsal fins, the 3.4 Kb mutant larvae were able to swim quite decently using the remaining anal and tail fins. To our surprise, some of them managed to reach adulthood (See Figure 2) and even reproduced (See Video 1). This was the story behind this venture, or at least the way I witnessed it. The rest, either you can read it in the paper, or belongs to every participant’s personal experience.
I could not finish without mentioning the fantastic work that everybody did over the last years to push this story forward. Elisa de la Calle-Mustienes, Joyce Pieretti, and Silvia Naranjo performed a terrific job in the transgenesis and genomics front. Tetsuya Nakamura and Juan Pascual-Anaya helped a lot with the µCT and lamprey in situ experiments, respectively. And finally, Nacho Maeso, who was at the heart and soul of all scientific discussions. Without them, and the humble medaka fish, this work would have never been possible.
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