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Staff Scientist/Research Assistant II – Pluripotent Stem Cells and Cartilage Biology

Posted by , on 10 October 2016

Closing Date: 15 March 2021

We are looking for an enthusiastic and highly motivated Staff Scientist or experienced Research Assistant/Technician to join the stem cell and regenerative medicine-based laboratory of Dr. April Craft, within the department of Orthopaedic Research at Boston Children’s Hospital and Harvard Medical School. Our lab studies the development of musculoskeletal tissues, primarily articular cartilage, using human pluripotent stem cells as a model system. Projects in the lab range from basic to translational research.

 

The candidate will be essentially involved in all aspects of the laboratory but will primarily focus on 1-2 prioritized scientific projects, including modeling of cartilage disorders using patient specific iPSCs. The successful candidate will work closely with the PI and post-doctoral fellows in the lab, and be responsible for maintaining human pluripotent stem cell differentiation cultures and analyzing/recording results using various established assays. Individualized research projects will be available based on proven experience and independence. Additional tasks include preparation of reagents and media, and a supporting role in lab supplies inventory/ordering and maintenance of lab equipment. Occasional weekend work is required. This job has physical requirements that include the ability to bend, lift and carry objects weighing up to 50 lbs on occasion, frequently reach and grasp objects above and below shoulder level, and occasional proofreading and checking documents for accuracy.

 

The applicant must be a US citizen or permanent resident. Applicants must have at least a BS/BA in Biomedical science (or equivalent); Candidates that have a MS or PhD degree are preferred. Applicants must have at least three years of cell culture experience, preferentially human embryonic stem cell culture, and a strong understanding of molecular biology. We will teach the right candidate the necessary skills. Salary will commensurate with experience. Excellent organization skills and communications skills in English are required. A minimum three-year commitment is requested, however this position is potentially long term.

 

Applicants should email a CV, contact information for three referees and a cover letter describing their background to april.craft@childrens.harvard.edu.

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Post-doctoral Position available – Cartilage Development and Disease, Pluripotent stem cells

Posted by , on 10 October 2016

Closing Date: 15 March 2021

We are looking for an outstanding, highly motivated postdoctoral fellow to join our innovative young department in the stem cell and regenerative medicine-focused laboratory of Dr. April Craft, Assistant Professor of Orthopaedic Surgery at Boston Children’s Hospital and Harvard Medical School. Our lab studies the development of musculoskeletal tissues, primarily cartilage, using human and mouse embryonic (ESCs) and induced pluripotent stem cells (iPSCs) as a model system. Available projects in the lab range from basic developmental biology to translational research. We are interested in applying our knowledge of how to generate cartilage tissues from pluripotent stem cells to further understand how genetic mutations cause skeletal dysplasias in patients, particularly those for which animal models do not exist. We have also recently identified a panel of molecular markers that may help to define progenitor cells that are best suited for cartilage regeneration and repair.

 

A strong background in one of the following fields is required: pluripotent stem cell biology, basic developmental biology, or musculoskeletal/cartilage development, homeostasis or disease. Candidates with hands on experience using pluripotent stem cells will be given preferential consideration. The successful candidate will have a recently acquired PhD or MD-PhD, a minimum of 3 years laboratory experience including tissue culture, and at least one first author publication. The candidate must be a US citizen or permanent resident, and must possess excellent communication & writing skills in English. Members of the Craft lab participate in seminar series and other events within the Harvard Stem Cell and Regenerative Biology Program, Boston Children’s Hospital Orthopaedic Research Laboratories, Harvard Stem Cell Institute, and Harvard Medical School.

 

Applicants should email a CV, contact information for three referees and a cover letter describing their background and research interests to april.craft@childrens.harvard.edu.

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PhD Position in Signal Transduction during Reproductive Plant Development

Posted by , on 10 October 2016

Closing Date: 15 March 2021

A Ph.D. position in molecular cell and developmental biology of plants is available in the lab of Prof. Kay Schneitz, Dept. of Plant Developmental Biology, Technical University of Munich in Freising/Germany. The successful candidate will work on the molecular characterization of the signaling pathway mediated by the atypical transmembrane receptor-like kinase STRUBBELIG (SUB) in Arabidopsis (1-4). The SUB pathway functionally links intercellular signaling controlled by receptor kinases and plasmodesmata, gateable channels interconnecting most plant cells, during tissue morphogenesis of for example flowers and ovules. Starting date is negotiable but ideally the position should be filled as soon as possible. The lab is part of the Collaborative Research Centre SFB924 (sfb924.wzw.tum.de) and thus funding comes from the German Research Council (DFG) and is at the usual EG13/2 level. Requirements are e.g. a German masters (with a mark of 2.5 or better), a French DEA (a final average of 13 or more), or a masters thesis. The person needs to have a firm basis in basic molecular techniques. Fluency in English is a must. Freising is located about 35 km to the north of Munich. Munich is a lively, cosmopolitan city close to beautiful lakes and the Alps. For further information please contact Kay Schneitz (kay.schneitz@tum.de) and visit the webpage (plantdev.wzw.tum.de).
(1) Chevalier et.al. 2005 PNAS 103: 9074-9079.
(2) Fulton et.al. 2009 PLoS Genetics 5: e1000355
(3) Vaddepalli et.al. 2011 PLoS One 6: e19730
(4) Vaddepalli et.al. 2014 Development 141: 4139-4148

Please contact:
Prof. Dr. Kay Schneitz
Plant Developmental Biology, TU München, D-85354 Freising
Email: kay.schneitz@tum.de URL: http://plantdev.wzw.tum.de

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From our sister journals – September 2016

Posted by , on 7 October 2016

Here we highlight some developmental biology related content from other journals published by The Company of Biologists.


CoB_BioOpen_AW

bio

Moran Neuhof, Michael Levin and Oded Rechavi explored the relationship between regeneration and inheritance in planaria 

 

shark

Ryo Nozu and colleagues provide evidence for lipid histotrophy in great white shark reproduction from a shark accidentally caught by fishermen in Okinawa.

 

ewald

Andrew Ewald and colleagues investigated the role of Twist1 in the dissemination of cells from epithelia.

 

CoB_DisModMech_AW_RGB

cantley

In an interview, Lewis Cantley, Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, talked about discovering the PI3K pathway and the relationship between metabolism and cancer

 

dmm-xu

Chunhui Xu and colleagues presented a human iPSC model for catecholaminergic polymorphic ventricular tachycardia.

 

dmm-swenson

Katherine Swenson-Fields and colleagues described a pathway for the differentiation of macrophages in polycistic kidney disease.

 

Journal typography

Editor-in-Chief Michael way took us through the good, the bad, and the median of journal impact factors.

 

jcs-bhat

Manzoor Bhat and colleagues described the role of tubulin polymerisation and stabilisation in neuronal development.

 

jcs-huber

Andrea Huber and colleagues reported an influence of semaphorin signalling on innervation and myoblast migration during diaphragm development.

 

jcs-kette

In some more work on myoblasts, Susanne-Filiz Önel and colleagues probed the role of Kette in Drosophila myoblast fusion.

 

Journal typography

jeb

Jesper Sørensen and colleagues explore the relationship between developmental plasticity and physiological acclimation in the adult, in the context of exposure to extremes of temperature

 

 

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Post-doc in evolutionary and developmental genetics at UPenn

Posted by , on 6 October 2016

Closing Date: 15 March 2021

We are seeking a creative and exceptionally motivated candidate to fill a post-doctoral position in the field of evolutionary and developmental genetics.

Research in the Kamberov lab is directed at uncovering the genetic basis of human adaptive traits, with a core focus on the evolution of skin appendages, namely sweat glands and hair follicles. In this pursuit, we utilize a highly interdisciplinary approach that combines mouse and human genetics with developmental biology and evolutionary genomics. The culmination of this research program is to not only enhance the understanding of human evolution but also to apply what we have learned in translational efforts that lead to the improvement of human health and alleviation of disease, particularly in the context of skin and skin appendage regeneration.

Projects include:
-Dissection of molecular pathways underlying skin appendage development and evolution.
-High throughput screening for regulatory elements controlling the specification and patterning of hair follicles and sweat glands.
-Dissection of stem cell populations in the skin and the regeneration of human skin appendages in vitro.
-Discovery and functional modeling of evolutionarily significant human variants using comparative genomics and humanized mouse models.

The position provides an exciting opportunity to work at the interface of basic and translational research in a collaborative and stimulating environment, and gain experience in a diverse set of technical approaches at the cutting edge of evolutionary, developmental and regenerative biology.

A doctorate in biology or related field is required. Applicants with a strong background in developmental biology, genetics, genomics or molecular biology are encouraged to apply. Prior experience with mouse genetics and husbandry is preferred.

Interested candidates should provide: 1) a CV 2) a brief letter detailing your interest in the lab and relevant past research experience 3) contact information for three references who can comment on your research. Application materials and any questions regarding the position should be addressed to Yana Kamberov: yana2@mail.med.upenn.edu

 

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Postdoctoral researcher position in developmental/stem cell biology-University of Sheffield

Posted by , on 6 October 2016

Closing Date: 15 March 2021

We are currently seeking an independent and motivated scientist to join the research group led by Dr Anestis Tsakiridis (https://www.sheffield.ac.uk/cscb/tsakiridis). His work focuses on dissecting the molecular basis of cell fate decisions in the developing embryo and aims to exploit this knowledge for disease-modelling and regenerative medicine applications. The group is particularly interested in the biology of neuromesodermal progenitors (NMPs), the bipotent cell population which drives embryonic axis elongation by generating spinal cord neuroectoderm and paraxial mesoderm.

We have recently described the efficient derivation of NMPs from human pluripotent stem cells (hPSCs) thus establishing a tractable system for studying these progenitors in vitro.  The ideal candidate will employ this model in combination with various screens and complementary approaches aiming to define the intrinsic and extrinsic determinants of NMP maintenance and differentiation. Applicants should hold a PhD in a related field and have experience in hPSC culture/differentiation, immunocytochemistry, high content imaging and chromatin immunoprecipitation. A background in Crispr/Cas9-based genome editing and/or bioinformatics would be highly advantageous.

To apply see:

http://www.jobs.ac.uk/job/AUQ660/research-associate/

For informal enquiries contact Anestis Tsakiridis  (a.tsakiridis[AT]sheffield.ac.uk)

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This month on the Node

Posted by , on 6 October 2016

September was notable for the amount of new jobs posted, from Kansas to Copenhagen to King’s College London, and PhD to tenure-track. Check out our jobs page for the latest opportunities. In case you missed them, here are some of our other monthly highlights:

 

Research

rui

 

Rui Monteiro and Tomasz Dobrzycki told us about where blood comes from and how it’s made.  Christopher Arnold and Alejandro Sánchez Alvarado wrote about the link between the microbiome and tissue regeneration in planaria.

 

Print

 

The IRB in Barcelona highlighted new research, recently published in Development, on how changes in gene expression accompany morphological changes during evolution, and another paper on centrosomes and cell shape in the trachea. DMDD told us about a new gene expression profile tool for wild type mice, and we highlighted August’s preprints of interest in our continuing feature.

 

People and ideas

ajohnston

We continued our ‘People behind the papers’ series with Adam Johnston, who talked about his recent work on mouse digit tip regeneration and his new lab in Canada. We also featured an interview with Lewis Cantley from Disease Models and Mechanisms.

 

Life beyond the bench

ctcs7hwwiaaan6o
A visual report from the Royal Society early career conference by Scriberian

 

reported from a Royal Society event for early career researchers on the future of science in the UK. Katherine Brown, executive editor of Development, introduced her recent interview with Retraction Watch on the changes to peer review that the journal is instigating.  Finally, Harrison Worrell wrote a report from a symposium celebrating 20 years since the birth of Dolly the sheep.

 

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Group Leader – Developmental Biology

Posted by , on 5 October 2016

Closing Date: 15 March 2021

The European Molecular Biology Laboratory is searching for Group Leaders.
EMBL offers a highly collaborative, uniquely international culture. It fosters top quality,
interdisciplinary research by promoting a vibrant environment consisting of young,
independent researchers with access to outstanding graduate students and postdoctoral fellows.

 
Group Leader
Developmental Biology
at EMBL Heidelberg, Germany

 

The Developmental Biology Unit studies the development of multicellular
organisms. Research in the unit covers all levels, from the cellular to
the whole organism, and is highly interdisciplinary, combining a wide
range of approaches and innovative techniques, with special emphasis
on quantitative and real-time imaging. Research in the unit is firmly
embedded within the overall EMBL research environment, with extensive
in-house collaborations and support from world-class services,
including the gene core, transgenic, metabolomics and mass-spectrometry
core facilities.

 
We are seeking outstanding candidates using model organisms to
address fundamental principles of multicellular development across the
entire spectrum of developmental biology. Complementary approaches,
including simplified systems, such as organoid and stem cell systems,
are also welcome. Candidates with strong background and research
using theoretical approaches are also encouraged to apply. There is the
possibility to hire two group leaders in the present call.

 
The successful candidate should have a strong motivation to work in
the multidisciplinary and collaborative environment of EMBL, grasping
the opportunity to interact with many other research groups. In general,
EMBL appoints group leaders early in their career and provides them
with a very supportive environment for their first independent position to
achieve highly ambitious and original research goals.

 
EMBL is an inclusive, equal opportunity employer offering attractive
conditions and benefits appropriate to an international research
organisation with a very collegial and family friendly working
environment. The remuneration package comprise a competitive
salary, a comprehensive pension scheme, medical, educational and
other social benefits, as well as financial support for relocation and
installation, including your family, and the availability of an excellent
child care facility on campus. EMBL is committed to achieving
gender balance and strongly encourages applications from women.
Appointment will be based on merit alone.

 

APPLICATION  INSTRUCTIONS

 
Please apply online through www.embl.org/jobs and include a cover letter, CV
and a concise description of research interests and future research plans.

 
Please also arrange for 3 letters of recommendation to be emailed directly by
your referees to references@embl.de at the latest by 20 October 2016.

 
Interviews are planned for 19 to 21 December 2016.
For further information about the position can be obtained from

the Head of Unit Anne Ephrussi (anne.ephrussi@embl.de).

 
Further details on Group Leader appointments can
be found under www.embl.org/gl_faq.

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September in preprints

Posted by , on 5 October 2016

Our monthly trawl for preprints from developmental biology and related research. Previous posts can be found here


 

Preprints roll on, and this month’s selection is a reminder of how developmental biology is based on a variety of model organisms. We’ve got two investigations into zebrafish mesoderm from Deborah Yelon’s lab, quite a bit of cell mechanics (in zebrafish, fly and worm), updates on the underlying cell biology of  cell division in c. elegans, a transcriptome for the spiny mouse, and much more besides.

 

michaux-et-al-fig-1c
Figure 1C from Robin, Michaux, et al. (Edwin Munro lab), showing dynamics of utrophin and myosin at the one cell stage of the c. elegans embryo

 

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

 

Developmental biology

PDGF signaling directs cardiomyocyte movement toward the midline during heart tube assembly. Joshua Bloomekatz, Reena Singh, Owen W.J. Prall, Ariel C. Dunn, Megan Vaughan, Chin-San Loo, Richard P. Harvey, Deborah Yelon

 

Hand2 Inhibits Kidney Specification While Promoting Vein Formation Within the Posterior Mesoderm. Elliot A. Perens, Zayra V. Garavito-Aguilar, Gina P. Guio-Vega, Karen T. Pena, Yocheved L. Schindler, Deborah Yelon

 

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

 

Zfp423 regulates Sonic hedgehog signaling via primary cilium function. Chen-Jei Hong, Bruce A. Hamilton

 

Heterozygous mutation to Chd8 causes macrocephaly and widespread alteration of neurodevelopmental transcriptional networks in mouse. Andrea L Gompers, Linda Su-Feher, Jacob Ellegood, Tyler W Stradleigh, Iva Zdilar, Nycole A Copping, Michael C Pride, Melanie D Schaffler, M Asrafuzzaman Riyadh, Gaurav Kaushik, Brandon Mannion, Ingrid Plajzer-Frick, Veena Afzal, Axel Visel, Len A Pennacchio, Diane Dickel, Jason P Lerch, Jacqueline N Crawley, Konstantinos S Zarbalis, Jill L Silverman, Alex S Nord

 

Landscape of X chromosome inactivation across human tissues. Taru Tukiainen, Alexandra-Chloé Villani, Angela Yen, Manuel A. Rivas, Jamie L. Marshall, Rahul Satija, Matt Aguirre, Laura Gauthier, Mark Fleharty, Andrew Kirby, Beryl B. Cummings, Stephane E. Castel, Konrad J. Karczewski, François Aguet, Andrea Byrnes, GTEx Consortium, Tuuli Lappalainen, Aviv Regev, Kristin G. Ardlie, Nir Hacohen, Daniel G. MacArthur

 

Genome-wide binding of posterior HOXA/D transcription factors reveals subgrouping and association with CTCF. Ivana Jerković, Daniel Murad Ibrahim, Guillaume Andrey, Stefan Haas, Peter Hansen, Catrin Janetzki, Irene González Navarrete, Peter Nick Robinson, Jochen Hecht, Stefan Mundlos

 

Differential gene expression in blastocysts following pronuclear transfer.  Edward H Morrow, Fiona C Ingleby

 

Excitable RhoA dynamics drive pulsed contractions in the early C. elegans embryo. François B Robin, Jonathan B Michaux, William M McFadden, Edwin M Munro

 

ATX-2, the C. elegans Ortholog of Human Ataxin-2, Regulates Centrosome Size and Microtubule Dynamics. Michael Stubenvoll, Jeffrey Medley, Miranda Irwin, Mi Hye Song

 

Synaptonemal complex components are required for meiotic checkpoint function in C. elegans. Tisha Bohr, Guinevere Ashley, Evan Eggleston, Kyra Firestone, Needhi Bhalla

 

Temporal regulation of epithelium formation. Stephen E Von Stetina, Jennifer J. Liang, Georgios Marnellos, Susan E Mango

 

Myosin II controls junction fluctuations to guide epithelial tissue ordering. Scott Curran, Charlotte Strandkvist, Jasper Bathmann, Marc de Gennes, Alexandre Kabla, Guillaume Salbreux, Buzz Baum

 

Geometry can provide long-range mechanical guidance for embryogenesis. Mahamar Dicko, Pierre Saramito, Jocelyn Etienne

 

Identification and Functional Characterization of Muscle Satellite Cells in Drosophila. Rajesh D. Gunage, Heinrich Reichert, K. VijayRaghavan

 

Translational control of gurken mRNA in Drosophila development. Christopher J Derrick, Timothy T Weil

 

Lipid metabolic perturbation is an early-onset phenotype in adult spin mutants: a Drosophila model for lysosomal storage disorders. Sarita hebbar, Avinash Khandelwal, Jayashree R, Samantha J Hindle, Yin Ning Chiang, Joanne Yew, Sean Sweeney, Dominik Schwudke

 

Regions of very low H3K27me3 partition the Drosophila genome into topological domains. Sherif El-Sharnouby, Bettina Fischer, Jose Paolo Magbanua, Benjamin Umans, Rosalyn Flower, Siew Woh Choo, Steven Russell, Rob White

 

Sexual dimorphism in the Drosophila metabolome increases throughout development. Fiona C Ingleby, Edward H Morrow

 

Cell Biology

Diverse roles of guanine nucleotide exchange factors in regulating collective cell migration. Assaf M Zaritsky, Yun-Yu Tseng, Angeles M. Rabadan, Michael Overholtzer, Gaudenz Danuser, Alan Hall

 

Laurdan and di-4-ANEPPDHQ probe different properties of the membrane. Mariana Amaro, Francesco Reina, Martin Hof, Christian Eggeling, Erdinc Sezgin

 

Heterogeneity of single-cell mechanical responses to tumorigenic factors. Aldo Leal-Egana, Gaelle Letort, Jean-Louis Martiel, Andreas Christ, Timothee Vignaud, Caroline Roelants, Odile Filhol, Manuel Thery

 

The FACT complex and cell cycle progression are essential to maintain asymmetric transcription factor partitioning during cell division. Eva Herrero, Sonia Stinus, Eleanor Bellows, Peter H Thorpe

 

Ankyrin G membrane partners drive the establishment and maintenance of the axon initial segment. Christophe Leterrier, Nadine Clerc, Fanny Rueda-Boroni, Audrey Montersino, Bénédicte Dargent, Francis Castets

 

 

Evolution etc.

Nuclear pore-like structures in a compartmentalized bacterium. Evgeny Sagulenko, Amanda Nouwens, Richard I Webb, Kathryn Green, Benjamin Yee, Gary Morgan, Andrew Leis, Kuo-Chang Lee, Margaret K Butler, Nicholas Chia, Uyen Thi Phuong Pham, Stinus Lindgreen, Ryan Catchpole, Anthony M Poole, John A. Fuerst

 

A structural variant in the 5′-flanking region of the TWIST2 gene affects melanocyte development in belted cattle. Niveditha Awasthi Mishra, Cord Drögemüller, Vidhya Jagannathan, Rémy Bruggmann, Julia Beck, Ekkehard Schütz, Bertram Brenig, Steffi Demmel, Simon Moser, Heidi Signer-Hasler, Aldona Pieńkowska-Schelling, Claude Schelling, Ronald Rongen, Stefan Rieder, Robert N. Kelsh, Nadia Mercader, Tosso Leeb

 

Contrasting genome dynamics between domesticated and wild yeasts. Jia-Xing Yue, Jing Li, Louise Aigrain, Johan Hallin, Karl Persson, Karen Oliver, Anders Bergström, Paul Coupland, Jonas Warringer, View ORCID ProfileMarco Cosentino Lagomarsino, Gilles Fischer, Richard Durbin, Gianni Liti

 

The genetic basis and fitness consequences of sperm midpiece size in deer mice. Heidi S Fisher, Emily Jacobs-Palmer, Jean-Marc Lassance, Hopi E Hoekstra

 

Mito-nuclear Incompatibilities and Mitochondrial Replacement Therapy. Adam Eyre-Walker

 

De novo transcriptome assembly for the spiny mouse (Acomys cahirinus). Jared Mamrot, Roxane Legaie, Stacey J Ellery, Trevor Wilson, David Gardner, David W Walker, Peter Temple-Smith, Anthony T Papenfuss, Hayley Dickinson

 

Indomethacin reproducibly induces metamorphosis in Cassiopea xamachana scyphistomae. Patricia Cabrales-Arellano, Tania Islas-Flores, Patricia E. Thomé, Marco A. Villanueva

 

Tools, techniques, resources, modelling

Zipper plot: visualizing transcriptional activity of genomic regions. Francisco Avila Cobos, Jasper Anckaert, Pieter-Jan Volders, Dries Rombaut, Jo Vandesompele, Katleen De Preter, Pieter Mestdagh

 

Mapping protein function with CRISPR/Cas9-mediated mutagenesis. Katherine F Donovan, Mudra Hegde, Meagan Sullender, Emma W Vaimberg, Cory M Johannessen, David E Root, View ORCID ProfileJohn G Doench

 

Glutton: large-scale integration of non-model organism transcriptome data for comparative analysis. Alan Medlar, Laura Laakso, Andreia Miraldo, Ari Löytynoja

 

Nanopore DNA Sequencing and Genome Assembly on the International Space Station. Sarah L Castro-Wallace, Charles Y Chiu, Kristen K John, Sarah E Stahl, Kathleen H Rubins, Alexa B. R. McIntyre, Jason P Dworkin, Mark L Lupisella, David J Smith, Douglas J Botkin, Timothy A Stephenson, Sissel Juul, Daniel J Turner, Fernando Izquierdo, Scot Federman, Doug Stryke, Sneha Somasekar, Noah Alexander, Guixia Yu, Christopher Mason, Aaron S Burton

 

PCR artifact in testing for homologous recombination in genomic editing in zebrafish. Minho Won, Igor B Dawid

 

Integrating tissue specific mechanisms into GWAS summary results. Alvaro Barbeira, Scott P Dickinson, Jason M Torres, Eric S Torstenson, Jiamao Zheng, Heather E Wheeler, Kaanan P Shah, Todd Edwards, GTEx Consortium, Dan Nicolae, Nancy J Cox, Hae Kyung Im

 

Comparing individual-based approaches to modelling the self-organization of multicellular tissues. James M. Osborne, Alexander G. Fletcher, Joseph M. Pitt-Francis, Philip K. Maini, David J. Gavaghan

 

The Drosophila Gene Expression Tool (DGET) for expression analyses. Yanhui Hu, Aram Comjean, Norbert Perrimon, Stephanie Mohr

 

Noise-processing by signaling networks. Styliani Kontogeorgaki, Ruben Sanchez-Garcia, Rob Ewing, Konstantinos Zygalakis, Ben D. MacArthur

 

Robust cell tracking in epithelial tissues through identification of maximum common subgraphs. Jochen Kursawe, Rémi Bardenet, Jeremiah J Zartman, Ruth E Baker, Alexander George Fletcher

 

 

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New phenotype screen examines causes of neonatal death

Posted by , on 4 October 2016

DMDD logo

This post first appeared on Annotations, the DMDD blog (blog.dmdd.org.uk).


Around a third of targeted gene knockouts in mice are embryonic-lethal. But not all deaths occur during gestation – a significant number of gene knockouts result in death at or shortly after the time of birth. Mice from these knockout lines provide a valuable animal model of human neonatal death and are the focus of a new systematic screen by the DMDD programme.

The study, to be carried out by consortium members at the Wellcome Trust Sanger Institute, will offer new insights into the genetic basis of death in neonates, complementing the efforts of large-scale human gene studies such as the DDD and UK10K.


UNDERSTANDING LETHALITY IN NEONATES

The DMDD programme studies embryonic-lethal knockout mouse lines, where lethal means that no pups are observed 14 days after birth (known as postnatal day P14). Detailed phenotyping of these lines can provide important clues about the genetic basis of human developmental disorders.

Our phenotyping efforts so far have focussed on in-utero development at embryonic days E9.5, E14.5 and E18.5 since, for the majority of embryonic-lethal lines, the embryos die well before birth.

In 5-10% of cases, however, the embryos die at the time of birth or shortly afterwards, and can provide an animal model of neonatal death due to genetic mutation. The pilot neonatal screen will study 20 of these lines during the period E18.5 to P14, gathering systematic phenotype data.

Nesting wild-type pups.
Nesting wild-type pups on their day of birth.

Common causes of lethality for neonates can include problems with partuition, breathing, suckling and achieving homeostasis. To understand the likely cause of death in each case, the neonatal screen will assess the pups’ gross dysmorphology, breathing, milk spot morphology (a test that reveals whether they have been able to feed), weight, measurements, locomotive skills, righting reflex (ability to correct their own body position) and blood glucose levels.

The first data is expected at the end of 2016. For more information about the DMDD programme, visit dmdd.org.uk.

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