PhD position in leukemic stem cells and metabolism
A PhD position is available in the laboratory of ‘’Stem Cells and Leukemia’’ at the University Clinic of Hematology & Central Hematology, Department of Biomedical Research (DBMR), Inselspital Bern, Switzerland. We are looking for a highly motivated and creative scientist with a master’s or MD degree to contribute to research projects aiming to explore leukemic stem cell dependencies and vulnerabilities using transgenic mouse models of myeloid malignancies and primary patient samples from leukemia patients. The employment starting date is 01.08.2020 (or negotiable).
Your profile
The applicant should have a master’s/diploma or MD degree. The potential candidate must be experienced in working with transgenic mouse models, and multicolor flow cytometry. Expertise in working with stem cell cultures, CRISPR/Cas9 gene manipulation techniques, and willingness to work with the primary patient samples are preferred. Demonstrated competence to independently conduct experiments and analyses, and willingness to collaborate internally and externally is mandatory. Applicant should have an excellent command of spoken and written English.
We offer you
The post-holder will be supported by a well-funded interdisciplinary research project in a young and dynamic environment. Our team works closely with clinicians and pharma industries in Switzerland and abroad. Department of Biomedical Research (DBMR) at the University of Bern and Inselspital Bern provides a stimulating environment and offers all the possibilities to be creative and highly productive. Doctoral thesis associated with an excellent qualification program. The PhD student will be enrolled in the interfaculty Graduate School for Cellular and Biomedical Sciences at the University of Bern (www.gcb.unibe.ch). The position is limited to 3 years with a possibility of extension. The salary will be according to the guidelines of the University of Bern.
Application / Contact
To apply for this position please submit your application in a single Pdf file including 1-page motivation letter specifying your research experience and interests, CV, summary of master thesis (max.one page), copies of master’s/diploma degree or MD degree, desired start date, and the names and contact details of 2-3 referees to: tata.nageswararao@dbmr.unibe.ch
Meeting report: 2nd EMBO workshop “Awakening of the genome: the maternal-to-zygotic transition”
Amanda Amodeo1*, Johanna Gassler2* and Ksenia Kuznetsova3*, Philip Zegerman4
*These authors contributed equally
Lewis-Sigler Institute for Integrative Genomics. Carl Icahn Laboratory Washington Rd., Princeton University. Princeton, NJ 08544
Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Dr. Bohr-Gasse 3, 1030 Vienna, Austria
Max Planck Institute of Molecular Cell Biology and Genetics Pfotenhauerstrasse 108, 01307 Dresden, Germany
Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Biochemistry, The Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge CB2 1QN, UK
Abstract
The fusion of gametes to form a zygote triggers the complex journey of embryogenesis. The first zygotic divisions are driven largely by maternal gene products, pre-loaded in the oocyte. One of the first steps in embryogenesis is the transition from the expression of the maternal genome to the expression of the new genome of the zygote – the maternal to zygotic transition (MZT). This transition is essential for the correct patterning and differentiation of the embryo and encompasses dramatic changes in genome organisation, chromatin state, cell cycle length and RNA stability. The MZT therefore offers a unique window to understand how fundamental aspects of cell and developmental biology are coordinated. Here we report highlights of the 2019 EMBO workshop “Awakening of the genome: the maternal-to-zygotic transition”, a unique synergy of insights from multiple disciplines and model systems into early metazoan development.
In the beginning……
The transition from the oocyte, a highly differentiated and arrested cell type, to a fertilised, developmentally active, totipotent cell requires dramatic changes in almost all aspects of cell physiology. Across species, an influx of calcium ions is required for egg activation and preparation of the oocyte for embryogenesis. One role of calcium ions is to trigger the activation of the phosphatase calcineurin, but how calcinuerin triggers multiple events during oocyte maturation is poorly understood. Using Drosophila oocyte activation as a model, Mariana Wolfner (Cornell University, US) presented a proteomic analysis of the changes in the phospho-proteome that occur in a calcineurin-dependent manner. The hundreds of proteins regulated by calcinuerin 1 provide a unique dataset to understand how the many changes that must occur during oocyte maturation are coordinated. One example of this is the critical translation regulator GNU, which, as described by Emir Avilés Pagán (Orr-Weaver lab, MIT, US), is phosphorylated and inhibited in arrested Drosophila oocytes by CDK, but gets dephosphorylated by calcineurin leading to activation of the GNU-binding kinase PNG. PNG is critical to trigger mRNA translation in the embryo by phosphorylating and inhibiting translational repressors, such as TRAL (Trailer Hitch), PUM (Pumilio) and BICC (Bicaudal-C) 2. This phosphorylation/dephosphorylation switch at the oocyte to embryo transition is a common feature among metazoa. Indeed Swathi Arur (MD Anderson Cancer Center, University of Texas, US) showed that in C. elegans the miRNA processing enzyme Dicer is inhibited by phosphorylation in the oocyte, but gets dephosphorylated after egg activation. This regulation is important to impede degradation of maternal RNA in the oocyte. It is clear that switching the phosphorylation state of many key proteins at the oocyte to embryo stage permits the rapid and wholesale changes in cellular physiology that must occur at this transition.
So long mother, and thanks for all the mRNA.
Oocytes are loaded with mRNA encoding between one third (mouse, C.elegans) to three quarters (Drosophila, sea urchins, fish) of all protein coding genes 3. Following egg activation, subsets of the maternal mRNA stores are degraded, first by maternally contributed factors (early mRNA decay) and then by zygotically expressed factors (late decay). The timing and order of these degradation events is critical for the onset of zygotic transcription and proper embryogenesis.
Several processes control mRNA stability including RNA binding proteins (RBPs), polyA tail length, miRNAs and RNA modification. In mice, mRNA decay begins already in the oocyte. Heng Yu Fan (Zhejiang University, China) demonstrated that the mRNA deadenylation machinery comprising of the CCR4-NOT complex together with the adaptor protein BTG4 are important for degradation of mRNA in the mouse oocyte. An additional pathway involving terminal uridylation of mRNAs by the TUT4/TUT7 enzymes also promotes maternal mRNA clearance both in the oocyte and in the embryo 4.
In Drosophila, RNA binding proteins play key roles in the timing of mRNA degradation and translation. Large scale analysis of ribonucleoprotein complexes in Drosophila presented by Craig Smibert (University of Toronto, Canada) suggested that a high affinity binding site of an mRNA towards a repressor, such as Pumilio would induce early mRNA decay, whereas degradation in later stage embryos required Pumilio-mRNA stabilisation by other factors, such as zygotically expressed miRNAs. These mechanisms could explain the temporal regulation of different transcripts in spite of the presence of Pumilio throughout early embryogenesis. Such a temporal order is also enforced by post-translational regulation of the RNA binding proteins themselves. Olivia Rissland (University of Colorado, US) described a screen in Drosophila for factors that degrade a key global mRNA regulatory complex, ME31B/Cup/TRAL during the MZT. These data provided evidence that differential degradation of RBPs might influence the timing and mechanisms by which transcripts are inhibited during embryogenesis.
In addition to mRNA stability, mRNA translation is also a critical regulatory step for gene expression at the MZT. Mike Sheets (University of Wisconsin, US) showed that Bicc1 (Bicaudal-C) in Xenopus laevis inhibits mRNA translation through direct binding to the mRNA 5. As spatial gradients of Bicaudal-C are established during oogenesis, this likely explains the maternal role of Bicc1 in determining anterior-posterior patterning. Despite this, not all Bicc1 target mRNAs are inhibited to the same extent, suggesting that other properties of the mRNA, such as translation efficiency may also be important. In line with this, Ariel Bazzini (Stowers Institute, US) showed that the best predictor of the half-life of an mRNA in human cells 6 as well as in zebrafish embryos 7 is its codon usage.
The plethora of pathways that exist to control mRNA stability and expression in the early embryo, likely reflects the importance of the exact timing and amount of protein production during development. However, using quantitative proteomics in mouse and Xenopus embryos respectively, Michele Boiani (MPI Munster, Germany) and Martin Wühr (Princeton University, US) showed that proteins remain relatively constant until the morula stage in mice 8 or the MBT (mid-blastula transition) in frogs. By separating nuclear from cytoplasmic protein, Martin Wühr showed in Xenopus that the nuclear fraction of the proteome changes during early development, which may explain some of the ordering of nuclear events during embryogenesis such as PolII versus PolIII transcription. Together with the multitude of pathways that regulate maternal mRNA, this suggests that post-translational regulation of maternal protein, including protein localization and modifications, must also be critical during the early embryonic cycles.
OK Child, over to you…. Setting up the transcriptional state of the zygote
The transition from maternal to zygotic control of the developing embryo requires not only the erasure of maternal RNA and proteins, but the activation of zygotic transcription. The reprogramming of parental DNA, combined with the correct timing of gene expression from the zygotic DNA requires major chromatin and transcriptional remodelling.
Nuclear organization of early pre-ZGA embryos is characterized by the absence of heterochromatin and the de novo acquisition of histone modifications and DNA methylation. Despite this, many chromatin-modifying enzymes, such as H3K9 methyltransferases, are expressed before the ZGA, raising the possibility that there are maternally-deposited inhibitors of heterochromatinisation. Mary Goll (University of Georgia, USA) provided evidence of one such inhibitor, the chromatin remodeller Smarca2 in zebrafish 9. Removal of Smarca2 is critical for global heterochromatin formation and interestingly Smarca2 clearance is driven by zygotic transcription of the miRNA miR-430, which links chromatin formation to the ZGA itself. Analysis of gene specific chromatin marks in Xenopus however, (Gert Jan Veenstra, Radboud University, Netherlands) demonstrated that several modifications, such as H3 K4 and H3 K27 trimethylation, arise in the absence of transcription in the early embryo. Indeed in Drosophila, Nicola Iovino (MPI Freiburg, Germany) showed that maternally inherited H3 K27 methylation is critical for inhibiting premature transcription before the ZGA 10. A similar role was proposed by Shifeng Xue (A Star, Singapore) for the chromosomal protein Smchd1 in zebrafish, whereby maternally supplied Smchd1 regulates DNA methylation and repression of embryonic genes. Therefore, both maternal and zygotic factors are important for determining the establishment of chromatin modifications and zygotic transcription.
Although the chromatin modification and DNA methylation landscape are remodelled in the early embryo, a key question is how this is directed to ensure that the right genes are turned on at the right time. Brad Cairns (University of Utah, USA) presented work in Zebrafish showing that key nucleosomes established before ZGA act as “placeholders” to determine the hypomethylated regions of the genome 11. At the ZGA these “placeholder” nucleosomes gain bivalency (the ability to switch between active and repressed epigenetic states) and are key determinants for turning housekeeping genes on, but developmental genes off. A critical feature of the placeholder nucleosomes is that they contain a histone variant (H2AZ). Genevieve Almouzni (Institut Curie, France) and Amanda Amodeo (Princeton University, USA) investigated the role of a different histone variant H3.3 during the ZGA in Xenopus and Drosophila. Amodeo demonstrated the large scale replacement of H3 by H3.3 on chromatin 12, although the functional significance of variant histone incorporation is poorly understood in Drosophila. However in Xenopus, Almouzni showed that the S31 residue which is specific to the H3.3 variant is uniquely essential for normal development through gastrulation 13. Together these results show an important role for histone variants in marking sites of future transcription and allowing normal developmental progression.
All hail the pioneers
The dramatic changes in chromatin during the ZGA are also accompanied by changes in transcription factor (TF) interactions with DNA. Whether chromatin modifications are a cause or a consequence of TF recruitment remains an important question. Of particular significance are the ‘pioneer’ factors, which are a unique class of TFs that bind to chromatin 14 and establish regions of accessibility and gene activation. A key pioneer factor in Drosophila is the transcriptional activator Zelda, which Melissa Harrison (University of Wisconsin, USA) demonstrated is needed continuously throughout early development for both the minor wave of zygotic transcription and the later major wave of transcription 15. How Zelda achieves transcriptional activation is poorly understood, but Chris Rushlow (NYU, USA) showed that Zelda modifies the probability, timing and rate of transcription of key downstream patterning genes 16. In contrast to Zelda, which is a global activator, Angela Stathopoulos (Caltech, USA) examined the role of broadly expressed repressors in the timing of ZGA in Drosophila. She found that both Runt and Su(H) act as position independent repressors in the pre-MZT Drosophila embryo 17. These findings suggest the possibility that competition between activators and repressors may be a general feature in the timing and spatial activation of different genes during ZGA.
To understand the timing of chromatin changes relative to TF factor binding Shelby Blythe (Northwestern, USA) used ATACseq in Drosophila embryos to show that cell fate specific chromatin states result from the binding of maternally deposited transcription factors on an initial ground state chromatin, pre-MBT 18. In zebrafish, Liyun Miao (Antonio Giraldez lab, Yale, USA) reported that key TFs of early transcription during zebrafish ZGA, Nanog/Oct4/SoxB1, are required to open the chromatin prior to histone acetylation. In addition, Daria Onichtchouk (University of Freiburg, Germany) used MNase seq to show that Nanog/Oct4/SoxB1 are initially recruited to high nucleosome affinity regions (HNARs) within the genome, while subsequently establishing open chromatin domains during ZGA 19. Consistently in Xenopus, Ken Cho (University of California, USA) showed that maternally deposited pioneer transcription factors such as Foxh1 pre-mark enhancers before transcription and before the generation of histone modifications 20. Together, these findings suggest that pioneer transcription factors may be upstream of transcription and chromatin changes during the ZGA across species. While the order of events is important, it is clear that we do not yet know all the factors involved in establishing transcriptional activation at the ZGA as Celia Alda-Catalinas (Wolf Reik lab, Babraham Institute, UK) presented a CRISPR screen in mouse ESCs, identifying new candidates that positively regulate genome activation 21.
ZGA in 3D
The emergence of totipotency and the subsequent specification of zygotic transcription at the ZGA results in major rearrangements in the spatial positioning and the 3D architecture of chromatin. Maria Elena Torres-Padilla (Helmholtz Institute, Munich, Germany) used Dam-ID to show that lamina associated domains (LADs) of chromosomes are established shortly after fertilization in a parental specific manner 22. Paternal LAD formation may be dependent on de novo establishment of H3K4 methylation providing new insights into the temporal order of chromatin architecture establishment in early embryos.
Topologically associated chromatin domains (TADs) are established during the MZT in Drosophila. Gabriel Cavalheiro (Eileen Furlong lab, EMBL, Germany) investigated which insulator proteins and TFs are required for TAD formation and demonstrated that distinct loci establish chromatin organization by different mechanisms. Interestingly using hybrid Drosophila embryos to distinguish between homologous chromosomes, Jelena Erceg, (Ting Wu lab, Harvard Medical School, USA) demonstrated the existence of trans-homolog TADs, which correlate with gene expression and Zelda binding 23.
To understand how pioneer factors physically change chromatin Thomas Quail (Jan Brugues lab, MPI Dresden, Germany) used reconstituted Xenopus egg extracts and fluorescent dCas9 to show that pioneer factor FoxA1 leads to increased rates of chromatin diffusion. While studies in zebrafish embryos presented by Nadine Vastenhouw (MPI Dresden, Germany) suggested that transcribed RNA together with RNA binding proteins are required for euchromatic domain establishment. Such organization might be explained by microphase separation of euchromatin, enabling interactions inside specific regions of the nucleus 24. Further evidence of such compartmentalisation was demonstrated by Ferenc Mueller (University of Birmingham, UK). Using live imaging of native transcription he showed that first transcription in zebrafish (prior to canonical ZGA), such as at the miR-430 locus, occurs in defined nuclear compartments 25, which may be a mechanism to safe-guard early transcription even before the embryo becomes permissive for bulk zygotic gene expression.
Transposon activation, the cost of pluripotency?
Up to 50% of the mammalian genome is made of integrated transposable elements (TEs). The majority of TEs (95%) are retroelements (ERVs, LINES, SINES etc). Reprogramming during early embryogenesis creates a dangerous window where TEs could be de-repressed. Small RNAs called piRNAs expressed in the embryo and germline repress LINE elements through transcriptional and post-transcriptional silencing. Donal O’Carroll (CRM, UK) presented a novel factor in mice called Spocd1 that represses LINE expression through DNA methylation. Despite this, young TEs show a peak of activation during early embryonic development and Didier Trono (EPFL, Switzerland) demonstrated that these young elements have a positive role in increasing chromatin accessibility and enabling human embryonic genome activation, but specialised repressors of the KZFP family (Krüppel-associated box (KRAB)-containing zinc finger proteins) are induced to silence these TEs in a negative feedback loop 26. Juanma Vaquerizas (MPI for Molecular Biomedicine, Muenster) presented a low input chromatin conformation capture technique (low-C) to study the link between TE activation and chromatin architecture and its influence on embryonic transcription 27. He demonstrated that the Murine Endogenous Retroviral Element (MuERV-L/MERVL) family of transposable elements drive the reorganisation of TAD boundaries and activation of a subset of genes in early 2-cell mouse embryo–like cells. Together these studies point towards roles for TE-based regulatory sequences as chromatin control elements, which are co-opted during embryonic development.
Cell cycle regulation in the early embryo
The oocyte to embryo transition is not only associated with transcriptional rewiring but is also associated with dramatic changes in cell cycle control across species. Marc Kirschner (Harvard Medical School, USA) described how the lengthening of the cell cycle is a primary event at the MBT in Xenopus, before the onset of bulk zygotic transcription and cell motility 28. The importance of the rapid early embryonic cell divisions was underscored by K. Neugebauer (Yale, USA) who showed that rapid cell-cycle signalling generates a significant energetic cost in the zebrafish embryo 29. Despite this, the fundamental functions of cell cycle control in coordinating events of the MBT remain poorly understood.
The lengthening of the cell cycle at the MBT is characterised by changes in replication timing during S-phase. Christopher Sansam (OMRF, USA) showed that in zebrafish, replication timing changes during the first 10 hours post fertilization with the most dramatic changes occurring on chromosome 4 30. Unlike Drosophila however 31, the global regulator of chromatin and replication timing Rif1 is not a major contributor to cell cycle length in zebrafish. A significant contributor to cell cycle lengthening is the DNA damage checkpoint, which in Drosophila is activated by transcription-replication conflicts 32. Anahi Molla-Herman (Huynh lab, Collège de France, France) showed that RNA-DNA hybrids formed at highly transcribed tRNA genes might be responsible for checkpoint activation and proper cell cycle timing at the MBT in Drosophila.
Outlook and conclusions
Understanding the coordination of dramatic changes in gene expression, chromatin remodelling, reprogramming, cell cycle as well as a host of other processes which characterise the oocyte to embryo transition requires the coming together of scientists from a multitude of disciplines. This topic benefits from the universality and evolutionary conservation of these control mechanisms as it brings together information from a host of model systems from planaria (Jochen Rink, MPI Dresden) to the marsupial fat-tailed dunnart (Stephen Frankenberg, University of Melbourne, Australia) and importantly to human embryos (Sanna Vuoristo, University of Helsinki, Finland). As quoted by Marc Kirschner “underlying the extreme complexity we may discover a simplicity which now escapes us” (FG Hopkins 1913). The 2019 EMBO workshop “Awakening of the genome: the maternal-to-zygotic transition” provided a unique opportunity to understand the simplicity behind how gametes are rewired to make embryos.
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Acknowledgements
We apologize to all those whose work we have not been able to include due to space limitations and we thank EMBO for funding this meeting. J.G. is supported by the European Research Council (ERC-StG-336460ChromHeritance to Kikuë Tachibana) and the L’Oréal Austria Fellowship for Women in Science and is an associated student of the DK Chromosome Dynamics (W1238-B20) supported by the Austrian Science Fund (FWF). K.K. is supported by the Max Planck Society and Deutsche Forschungsgemeinschaft (DFG, SPP2191).
Welcome to our monthly trawl for developmental biology (and related) preprints.
In lock down you might find yourself with more time to read; reading some science might also be a welcome distraction from the pandemic. Lots of fascinating stuff in March, hosted on bioRxivand arXiv– let us know if we missed anything. Use these links to get to the section you want:
Structural and developmental principles of neuropil assembly in C. elegans
Mark W. Moyle, Kristopher M. Barnes, Manik Kuchroo, Alex Gonopolskiy, Leighton H. Duncan, Titas Sengupta, Lin Shao, Min Guo, Anthony Santella, Ryan Christensen, Abhishek Kumar, Yicong Wu, Kevin R. Moon, Guy Wolf, Smita Krishnaswamy, Zhirong Bao, Hari Shroff, William Mohler, Daniel A. Colón-Ramos
Dynamic Sex Chromosome Expression in Drosophila Male Germ Cells
Sharvani Mahadevaraju, Justin M. Fear, Miriam Akeju, Brian J. Galletta, Mara MLS. Pinheiro, Camila C. Avelino, Diogo C. Cabral-de-Mello, Katie Conlon, Stafania Dell’Orso, Zelalem Demere, Kush Mansuria, Carolina A. Mendonça, Octavio M. Palacios-Gimenez, Eli Ross, Max Savery, Kevin Yu, Harold E. Smith, Vittorio Sartorelli, Nasser M. Rusan, Maria D. Vibranovski, Erika Matunis, Brian Oliver
Defining totipotency using criteria of increasing stringency
Eszter Posfai, John Paul Schell, Adrian Janiszewski, Isidora Rovic, Alexander Murray, Brian Bradshaw, Tine Pardon, Mouna El Bakkali, Irene Talon, Natalie De Geest, Pankaj Kumar, San Kit To, Sophie Petropoulos, Andrea Jurisicova, Vincent Pasque, Fredrik Lanner, Janet Rossant
Timing of organ initiation is crucial for robust organ size
Mingyuan Zhu, Weiwei Chen, Vincent Mirabet, Lilan Hong, Simone Bovio, Soeren Strauss, Erich M. Schwarz, Satoru Tsugawa, Zhou Wang, Richard S. Smith, Chun-Biu Li, Olivier Hamant, Arezki Boudaoud, Adrienne H. K. Roeder
A new role for histone demethylases in the maintenance of plant genome integrity
Javier Antunez-Sanchez, Matthew Naish, Juan Sebastian Ramirez-Prado, Sho Ohno, Ying Huang, Alexander Dawson, Deborah Manza-Mianza, Federico Ariel, Cecile Raynaud, Anjar Wilbowo, Josquin Daron, Minako Ueda, David Latrasse, R. Keith Slotkin, Detlef Weigel, Moussa Benhamed, Jose Gutierrez-Marcos
Embryo-like features in developing Bacillus subtilis biofilms
Momir Futo, Luka Opašić, Sara Koska, Nina Čorak, Tin Široki, Vaishnavi Ravikumar, Annika Thorsell, Domagoj Kifer, Mirjana Domazet-Lošo, Kristian Vlahoviček, Ivan Mijaković, Tomislav Domazet-Lošo
Midbody remnant inheritance is regulated by the ESCRT subunit CHMP4C
Javier Casares-Arias, María Ujué Gonzalez, Alvaro San Paulo, Leandro N. Ventimiglia, Jessica B. A. Sadler, David G. Miguez, Leticia Labat-de-Hoz, Armando Rubio-Ramos, Laura Rangel, Miguel Bernabé-Rubio, Jaime Fernández-Barrera, Isabel Correas, Juan Martín-Serrano, Miguel A. Alonso
Conserved epigenetic regulatory logic infers genes governing cell identity
Woo Jun Shim, Enakshi Sinniah, Jun Xu, Burcu Vitrinel, Michael Alexanian, Gaia Andreoletti, Sophie Shen, Brad Balderson, Guangdun Peng, Naihe Jing, Yuliangzi Sun, Yuliang Wang, Patrick P L Tam, Aaron Smith, Michael Piper, Lionel Christiaen, Quan Nguyen, Mikael Bodén, Nathan J. Palpant
Content and performance of the MiniMUGA genotyping array, a new tool to improve rigor and reproducibility in mouse research
John Sebastian Sigmon, Matthew W Blanchard, Ralph S Baric, Timothy A Bell, Jennifer Brennan, Gudrun A Brockmann, A Wesley Burks, J Mauro Calabrese, Kathleen M Caron, Richard E Cheney, Dominic Ciavatta, Frank Conlon, David B Darr, James Faber, Craig Franklin, Timothy R Gershon, Lisa Gralinski, Bin Gu, Christiann H Gaines, Robert S Hagan, Ernest G Heimsath, Mark T Heise, Pablo Hock, Folami Ideraabdullah, J. Charles Jennette, Tal Kafri, Anwica Kashfeen, Samir Kelada, Mike Kulis, Vivek Kumar, Colton Linnertz, Alessandra Livraghi-Butrico, Kent Lloyd, Richard Loeser, Cathleen Lutz, Rachel M Lynch, Terry Magnuson, Glenn K Matsushima, Rachel McMullan, Darla Miller, Karen L Mohlke, Sheryl S Moy, Caroline Murphy, Maya Najarian, Lori O’Brien, Abraham A Palmer, Benjamin D Philpot, Scott Randell, Laura Reinholdt, Yuyu Ren, Steve Rockwood, Allison R Rogala, Avani Saraswatula, Christopher M Sasseti, Jonathan C Schisler, Sarah A Schoenrock, Ginger Shaw, John R Shorter, Clare M Smith, Celine L St. Pierre, Lisa M Tarantino, David W Threadgill, William Valdar, Barbara J Vilen, Keegan Wardwell, Jason K Whitmire, Lucy Williams, Mark Zylka, Martin T Ferris, Leonard McMillan, Fernando Pardo-Manuel de Villena
Comparing quality of reporting between preprints and peer-reviewed articles in the biomedical literature
Clarissa F. D. Carneiro, Victor G. S. Queiroz, Thiago C. Moulin, Carlos A. M. Carvalho, Clarissa B. Haas, Danielle Rayêe, David E. Henshall, Evandro A. De-Souza, Felippe E. Amorim, Flávia Z. Boos, Gerson D. Guercio, Igor R. Costa, Karina L. Hajdu, Lieve van Egmond, Martin Modrák, Pedro B. Tan, Richard J. Abdill, Steven J. Burgess, Sylvia F. S. Guerra, Vanessa T. Bortoluzzi, Olavo B. Amaral
The Centre for Integrative Biology of Toulouse (CBI) is looking to strengthen its strong research community in Cellular and Developmental Biology. Existing groups investigate numerous aspects from cell division, morphogenesis to progenitor/stem cell biology using model organisms. Candidates complementing or reinforcing this community are encouraged to apply. Particular attention will be given to interdisciplinary, experimental and/or theoretical projects encompassing biophysics, systems biology and/or computational approaches. Further information can be found on the CBI website (http://cbi-toulouse.fr/eng/accueil-nouvelles-equipes) or by contacting Patrick Blader directly (patrick.blader@univ-tlse3.fr).
Autoradiograph of the first genetic fingerprint, together with Alec Jeffreys’ lab book describing the experiment. 1984. Wellcome Images, CC-BY 4.0 Via Wikimedia Commons
35 years ago this month, a small team of scientists at the University of Leicester published a paper in the journal Nature that changed the world. Written by Alec Jeffreys, Victoria Wilson and Swee Lay Thein, the title, ‘Hypervariable ‘minisatellite’ regions in human DNA’ and the jargon-filled results talking about dispersed tandem-repeats and allelic variations don’t provide much of a clue unless you know what you’re looking at.
But it’s this last sentence of the abstract that’s the real giveaway: “A probe based on a tandem-repeat of the core sequence can detect many highly variable loci simultaneously and can provide an individual-specific DNA ‘fingerprint’ of general use in human genetic analysis.”
In the latest episode of Genetics Unzipped, we take a look at the story of genetic fingerprinting, and some of the very first ways in which this game-changing technique was put to work.
If you enjoy the show, please do rate and review on Apple podcasts and help to spread the word on social media. And you can always send feedback and suggestions for future episodes and guests to podcast@geneticsunzipped.com Follow us on Twitter – @geneticsunzip
A couple of weeks ago we posted a collection of tweets from scientists about COVID-19. A lot has changed since that time – we in the UK are two days in to our own lock down, along with many parts of the world – and so we thought it would be a good time to share some more perspectives from the science Twittershere in the time of the pandemic. You’ll hopefully find some of it is useful, some thought-provoking, and some light-hearted. Feel free to share any other online nuggets in the comments.
Firstly, remember it’s a pandemic
Dear all in HE: this is NOT an ‘opportunity’ – it is not a ‘great time to write’. It is a global pandemic. People are dying. There is no possibility of ‘business as usual’ and the very idea is abhorrent. This discourse shows how broken things have become.
— Professor Janet Goodall (@janetifimust) March 22, 2020
Academic peeps: I've lived through many disasters. Here is my advice on "productivity". First, play the long game. Your peers who are trying to work as normal right now are going to burn out fast. They're doomed. Make a plan with a longer vision. /1
I'm pretty tired of hearing how we scientists are supposed to be so productive now. Anyone with kids, elderly parents, lab members to worry about, stranded masters students, etc is too stressed and busy to be thinking big thoughts.
Hey fellow PIs. If you are in #COVID19 hotspot area and your institute/University does not have the guts to close down, send the people in your lab home. We Are Scientists. We understand. Unless you are a virologist, your work can wait! Plus, home office can be productive for us.
Hi folks, as no experiments for the next 6-8 weeks, I'm interested in taking some online courses on image processing/analysis, machine learning, Python, ImageJ/Fiji, microscopy, fundamental optics, etc. Any recommendations?
To aid remote teaching & learning as #COVID19 shuts down classrooms, we’re providing free access to all our educational science video content through June 15.
To help beat the stress of COVID quarantine, I'm going to start a thread with fun microscopy-related resources. One a day (from me) to keep things fresh. Please add! #SciTwitter#Microscopy
Dear Post-docs and PhD students, Even if there's no computational (i.e. bioinformatic) aspect to your research, some coding is useful to know. If your lab has closed and you've had time to recover (take care of your emotional needs in such an upheaval) consider learning some!
I've received numerous requests from bench biologists asking for bioinformatics tutorials to work through. In response @sinabooeshaghi and I will teach a #scRNAseq @zoom_us workshop (for up to 300) on Thursday March 26th @ 1pm PST. Join us at https://t.co/5UPjJ3WxlRpic.twitter.com/1spevy08Y4
As we transition to remote work, we look for ways to continue contributing to the research community.
For other #Drosophila folks in a similar situation, when you feel ready, here are just a few ideas:
— DRSC-BTRR & DRSC-TRiP at Harvard Med School (@DRSC_TRiP) March 18, 2020
Folks with invertebrate cultures in your labs- as we reduce/ stop lab work, it would be very helpful to know who has what cultures so we don't lose some. @Hejnol_Lab and I started a google spreadsheet to coordinate – https://t.co/hXa4LoRc3O . Email or dm to get write access
Our lab online-collaborated on this piece, sharing our experience in dealing with the current #COVIDー19 crisis, – hopefully helpful (also in the future). https://t.co/uwnbX5ZTmF
There's lots to do doing a #lablockdown: most importantly staying safe & looking after your mental health. If you plan to use some time thinking about your career, @pcabezaspadilla and I have written an @embl blog article on where to start:https://t.co/ssZLPqqUmK#ecrchat
Tip for online group meeting: on zoom pro we split the group into pairs, and asked them to listen to each other about how the current situation affects them. Effective and fun way to get sympathetic listening.
EEB tweeps: Sad your conference has been cancelled? Still want to meet new colleagues and learn about new science? Bored while social distancing at home and want to gain experience mentoring or peer reviewing? Join our pilot "Zoom-a-review" program @BehavEcol@ASNAmNat (1/6)
. @UCSF peeps: to try to keep some semblance of community, we are replacing the Basic Science Seminar Series with a faculty zoom series. PIs-> please fill out the Doodle poll (yes I know). Trainees-> encourage your PIs to talk about your work. Deadline this Friday. Thanks
The next person who tweets about how productive Isaac Newton was while working from home gets my three year old posted to them. pic.twitter.com/ZPKTyLnEeL
Thinking about home schooling (KS1 Year 1). For science, one fun thing would be to pose a question each week (e.g. "How does evaporation work?"), then help son design experiment, and spend the week doing & writing up together. Other ideas for fun, testable science questions?
Want your homeschooling to include fun, collaborative science experimentation? Read about our impromptu #HomeSci Twitter project! https://t.co/DGZSSvtqk8
Are you a parent trying to find activities for kids home from school? Or someone stuck at home looking for fun distractions? Here are some fun, free science and nature resources you can use at home. I’ll be adding to this list over time.
Pro-tip for couples suddenly working from home together: Get yourselves an imaginary coworker to blame things on. In our apartment, Cheryl keeps leaving her dirty water cups all over the place and we really don't know what to do about her.
— Prof Richard Johnston (@DrRichJohnston) March 18, 2020
The great Bill Wood, with "Six Feet Apart or Six Feet Under." Bill, now retired, was a giant of phage and worm genetics and science education, but was also a folk singer in Cambridge, recording with Joan Baez in 1959. https://t.co/TOeb34riFnpic.twitter.com/jQsgCiG0t2
For all those experimental scientists trapped at home with acute lab-withdrawal here a video to play on loop on your computer. I made a special soothing buffer for you this morning. Students, postdocs & junior faculty you are not alone, together we get through this! pic.twitter.com/PRvL0wojAA
As labs shut down in response to the coronavirus pandemic, some might be unsure of what to do next. Even if your project doesn’t have a computational (i.e. bioinformatic) aspect, knowing some code can still be useful to present your research. Importantly, learning to code is particularly well-suited for the current situation, because there are a lot of free resources online that make it possible to learn by yourself with just a computer.
Before I go any further, I must acknowledge that during this time, many researchers will find themselves in a strange and stressful situation to which everyone will react differently. Although some will see this as an opportunity, others might feel they should be productive and find that they are unable, because they don’t have the resources, emotional energy or time, especially if they’re now taking on additional responsibilities such caring for children full time etc. The suggestions in this post are just that – suggestions – something to do if you are bored. They are not requirements or necessities. Should you feel that you’re under too much of a burden then try something else instead or – and this is important too – just try to rest. Please do not feel that you need to be productive. We should support everyone’s unique situation, rather than compare it our own response and responsibilities.
An additional disclaimer: I am, by no means, a coding expert. The coding languages I suggest are based on the fact that they can be used for universal tasks in academia (and beyond), and that they are simple enough to pick up and produce something useful without knowing the whole language. However, it’s unlikely I’ll be able to help with any specific problems! It’s also important to recognise that coding can be frustrating and time-consuming. Sometimes, it can be a case of a learning through a lot of trial and error, or you might find you copy code without ever understanding how it works. Both are fine and, if want to persevere, remember to be patient with yourself.
Below I’ve introduced three coding languages. To start, I recommend picking just one and setting yourself a small goal of what you would like to do with it. I find that it can sometimes be difficult to know where to start if you’re not really sure what you want to end up with!
1. LaTeX
Pronounced “Lay-tek”, LaTeX is a coding language that is used for preparing, formatting and producing written documents. It can be useful for putting together a formatted version of your preprint or writing your thesis. The bonus here is that, since it is written in code, the file size is quite small, which makes it less likely to crash when producing large documents. It is also great at integrating mathematical equations and figures, and integrates with reference management software to produce bibliographies. Perhaps most importantly, it uses a nice font(!)
The hardest thing about using LaTeX is knowing which software to use. There are several different apps (usually with ‘tex’ somewhere in the name) that allow you to write in LaTeX and compile a document. To be honest, I have no idea which one is best or indeed the difference between them (I use TeXShop). To start off with, I recommend using Overleaf, which is free for personal and uses a web-browser, so no need to download anything. They also provide a number of useful tutorials and walkthroughs to get started. There are also plenty of other research sites that you can find with a quick Google search. To begin with, you could try:
Producing a thesis cover page.
Producing a cover letter for a job application.
Writing your C.V.
Formatting a figure and figure legend.
2. R
R is a very powerful language that can be used for all types of statistical data analysis and presentation. All I know how to do with it, however, is how to turn an excel file into a graph. As R is so powerful, even the introductory resources can be quite complex and quickly dive-in to specialist terminology. I recommend this introductory workshop (still in early phases of being put together) by DataCarpentry. As a side-note they run some great workshops on a number of different coding languages and I would recommend attending if you get the chance. In addition, sometimes it’s best just to Google what you want to do, copy that code and learn yourself through tweaking it here and there. This approach isn’t so different from wet-lab research: imagine, for example, that R is your model organism and your knocking-in and knocking-out genes – with instant results! To start off with you could try:
Producing a bar graph and formatting the font, colours and axes.
HTML provides a basic language for producing websites and CSS is used to make them look better. Some fundamental knowledge of these can help when trying to customise your lab website or formatting a blog post. You don’t need any specialist software, you can just use Notepad or TextEdit to create the file (save the files with .html or .css and they’re converted automatically and will open in your browser), although some programmes do make it easier when starting out by colour-coding parts of code. Again, tons of material is provided online. A good start for learning HTML is provided in this tutorial from w3schools.com and the CSS intro is very good too. As always, Google is your friend. Why not experiment by:
Producing a simple homepage for a website?
Writing a blog post (for the Node, maybe?) introducing some HTML elements?
Presenting your data in a HTML table?
Customising an existing HTML file with your own CSS code?
If a group would like to start learning together, it might be a good idea to start a Slack group to support each other! If you have any other suggestions on languages to add to this post, please comment or add to the Twitter thread. For other suggestions for what to do outside of the lab, check out this great infographic from Dr Zoë Ayres. Why not write use your new skills to a post for the Node on one of these ideas?
Last week, I and the rest of the Development team said goodbye to our lovely office, and a new era of remote working has begun. But we’re lucky – editorial work can (we hope!) proceed pretty much as normal from our desks at home. Of course, things are not so easy for researchers: shutting down a lab means a lot more than moving your monitor and keyboard to a new location and figuring out the best ways to maintain good communication with your colleagues.
Across the globe, normal life and normal work is on hold for the foreseeable future, and – while there are far more important things to worry about – this will inevitably impact on researchers’ ability to publish their work. The Development editorial team has been thinking about what we can do to support our community during this time, and we’ve just released the following statement (which you can also read here):
We are of course aware that the COVID-19 pandemic is having an unprecedented impact on researchers worldwide, with many labs shutting down either partially or fully. The Editors of all The Company of Biologists’ journals have been considering ways in which we can alleviate concerns that members of our community may have around publishing activities during this time. Here, we detail the actions we are taking at this point:
Any reviewer or author unable to meet deadlines set by the journal should contact the editorial office and we will be able to extend your deadline. Our Academic Editors may also be somewhat delayed in handling papers as they deal with pressing matters – we hope that all parties will recognise the need for increased flexibility with timelines during this period. Please note that reviewers will still receive automated reminders from our system, but these are not intended to put you under increased pressure so please just let us now if you need extra time.
Our scoop protection policy means you don’t need to worry about being scooped once you’ve submitted your manuscript – even if your revisions take longer than expected. Moreover, we will not necessarily reject a new submission if a competing paper has just been published: in these cases, we encourage authors to contact us to discuss how to proceed.
We ask that reviewers bear in mind that authors may be unable to conduct experimental revisions for a paper. Obviously the journal needs to ensure that submissions are held to the same standards as usual, and that all conclusions drawn in a paper are supported by the data presented, but ask reviewers to limit requests for experimental revisions to those they deem essential for publication in the journal.
Where authors are concerned about their ability to respond to reviewers’ reports, we encourage you to contact the editorial office to discuss their revision further. Please send us a point-by-point response indicating where you are able to address concerns raised (either experimentally or by changes to the text) and where you will not be able to do so within the normal timeframe of a revision. The editor will then provide further guidance.
We hope these policies will help to support authors during these difficult times; we will continue to review the situation going forwards. Please don’t hesitate to contact the editorial office if you have any questions or concerns.
And at this time when many researchers are unable to conduct experiments, remember that Development welcomes the submission of purely computational or theoretical papers!
As many of you will be aware, The Company of Biologists also organises workshops and meetings that have been affected by the pandemic. All our events through to the end of July have been postponed, and we will continue to review the situation for events later in the year. We’re still hoping to be able to hold our ‘From Stem Cells to Human Development’ meeting in September, but recognise that no-one wants to be booking conferences at this time and so have made some changes to our deadlines and registration process – you can find more information on this here.
In these crazy times, communities (be they personal or professional) seem more important than ever – so while we won’t be meeting in person any time soon, I’m looking forward to seeing the innovative ways we’ll find to interact virtually, and I’d be happy to hear any ideas you may have about how Development and The Node can help with this. Feel free to comment below, get in touch on twitter (@katemmabrown1) or drop me an email.
And in the meantime, stay safe, stay at home and wash your hands!
CENTURI is recruiting up to 8 Postdocs to start in October 2020, for two years! Recruited candidates will join our vibrant interdisciplinary community in Marseille (France).
Applications to our call will be open until April 17. Candidates can either apply to one of the advertised CENTURI projects or submit their own project, providing that they meet the application criteria and that their application is supported by at least 2 host labs.
In-person interviews for shortlisted candidates will take place onJune 18 and 19.
Please note that due to the current health situation, the in-person interviews might be replaced with visioconferences.
Postdoctoral fellows will work in an interdisciplinary life science environment, and have backgrounds in any of the following fields: cell or developmental biology, immunology, neurobiology, biophysics, theoretical physics, computer science, bioinformatics, applied mathematics, engineering.
Postdoctoral fellows will be co-supervised by two or three supervisors from our community.
Our Postdoc call 2020 agenda:
Publication of projects and opening of the call for candidates: March 17 – April 17, 2020
Preselection of candidates (PIs and ad hoc committee): April 20 – May 8, 2020
CENTURI brings together leading institutes in biology, physics, mathematics, computer science and engineering to decipher the complexity and dynamics of living systems. CENTURI offers an exceptional international environment for the development of interdisciplinary projects, in developmental biology, immunology and neurosciences.
CENTURI is mainly located on the Luminy campus of Aix-Marseille University and is affiliated to Aix- Marseille University, CNRS, INSERM and École Centrale Marseille.
BSDB/GenSoc 2020 had a fantastic planned line up of plenary speakers. Over the past three days we managed to sit down for a virtual chat with five of them – in these short videos, you’ll hear about their science, their connection to the BSDB, how the coronavirus has been affecting their labs, and more.
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