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Postdoctoral Positions – RNA pathways in development and disease – NIH/NCI

Posted by , on 19 April 2018

Closing Date: 15 March 2021

We have open postdoctoral positions in our lab. We are looking for researchers interested in understanding the mechanisms through which non-coding RNAs and RNA metabolic pathways regulate gene expression in mammals and how these mechanisms impact animal development and disease. Our lab uses a combination of mouse models and genetic tools together with biochemical and computational approaches to stringently define the roles of these pathways in vivo.

To learn more about our research go to our website at vidigallab.com

 

Research Focus
Summary of Research focus

 

Who you are:

  • You share our enthusiasm for RNA biology, gene regulation, mouse development, and tumor biology
  • You have PhD-experience in one or more of the following: RNA biology, mouse genetics, developmental biology, tumorigenesis, massively-parallel sequencing techniques, or computational biology.

 

What we offer:

  • Fully-funded postdoc positions.
  • A stimulating and collaborative environment.
  • Opportunity to start your own research program or lead ongoing projects.

 

Apply: Send the following to vidigal.lab@gmail.com

  • 2 paragraph cover letter explaining your scientific trajectory and why you would like to join us.
  • CV and email contacts for 3 references.

 

NIH is dedicated to building a diverse community in its training and employment programs. This position is subject to a background investigation.

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The people behind the papers – Sa Geng & James Umen

Posted by , on 19 April 2018

The transition to multicellularity in eukaryotes appears to be intimately linked to the transition from isogamy (gametes of the same size) to anisogamy (gametes of distinct sizes), and indeed to oogamy, a form of anisogamy with a large, immotile egg and a motile sperm. Volvocine algae provide a useful and fascinating model to study how this transition occurred, and a new paper in Development explores the genetics of the process in Volvox and some of its relatives. We caught up with first author Sa Geng and his PI James Umen, Joseph Varner Distinguished Investigator at the Donald Danforth Plant Science Center in St. Louis Missouri, to hear the story behind the work.

 

Sa and James in situ

 

James, can you give us your scientific biography and the questions your lab is trying to answer?

JU I was a PhD student at University of California, San Francisco where I studied yeast pre-mRNA splicing in Dr. Christine Guthrie’s laboratory. I moved to Dr. Ursula Goodenough’s laboratory at Washington University as a postdoc to work on the mechanism of chloroplast DNA inheritance and its control by mating type in the green alga Chlamydomonas. During that time we made a somewhat fortuitous discovery of a mutation in the Chlamydomonas retinoblastoma tumor suppressor gene that initiated an interest in cell size control, a problem which we have continued to work on in my own laboratory. During my stay in the Goodenough laboratory we had joint meetings with Dr. David Kirk’s group who were doing research at the forefront of Volvox developmental biology. My exposure to Volvox and my attendance of a class on the emerging field of evolution and development catalyzed a long-term interest in pursuing an integrative program of cell, developmental and evolutionary biology in volvocine algae (i.e. Chlamydomonas, Volvox and other multicellular relatives) in order to gain a better understanding of how ancestral genetic and cell biological mechanisms are co-opted and how new ones evolve during the transition to multicellularity.

A major question associated with the transition to multicellularity is the evolution and origin of male and female sexes; but tackling this problem seemed like a distant goal when I began my first independent position at Salk Institute in San Diego in 2002. By the time I moved my laboratory to Danforth Plant Science Center in 2011 volvocine algae had entered the era of modern genomics which gave us new tools and information for investigating the transition to multicellularity and evolution of sexes. Besides our work on cell size control and evolution of multicellularity, we also became interested in the control of intracellular carbon partitioning in algae which has some important practical implications for sustainable production of lipid-based biofuels and other bioproducts.

 

And Sa, how did you come to be involved with this project?

SG When I joined the Umen lab, the function of Volvox MID had not been tested and some of the important methods we needed such as transformation of Volvox and sexual crosses were not yet firmly established. After optimizing those methods we figured out the spermatogenesis function of MID in Volvox and I became curious how MID evolved in algae and when it acquired the function to drive spermatogenesis. To answer these questions, I did cross-species MID transformation, putting GpMID and PsMID into female Volvox.

 

Volvocine algal gamete dimorphism and phylogenetic relationships, from Fig. 1 in the paper

 

What makes volvocine algae useful models for evolutionary developmental biology?Are they easy models to work with on a day-to-day basis?

SG&JU From an evolutionary and taxonomic perspective volvocine algae are unique in being closely related, yet encompassing a graded series of multicellular innovations. They range from the well-studied model unicellular alga Chlamydomonas reinhardtii, to simple genera with small groups of coherently-organized undifferentiated cells, all the way to species like Volvox carteri that evolved a relatively complex pattern of morphogenesis, complete germ-soma division of labor, and oogamy. The haploid genomes of Chlamydomonas, Volvox, and other sequenced volvocine species have low genetic redundancy (no whole genome duplications) and are quite similar to each other in terms of gene content and gene number, prompting the question of how evolutionary innovations arose among organisms with such similar genetic toolkits. Both Chlamydomonas and Volvox (and other volvocine species) are relatively easy to culture and have short generation times. Besides classical genetics they have an expanding set of molecular genetic tools such as transformation, RNAi and CRISPR-based gene editing. Using these tools, it is now possible to test hypotheses about how gene/protein functions change (or not) in association with developmental innovations.

 

Can you give us the key results of the paper in a paragraph?

SG&JU Prior to our study we knew that a transcription factor called Mid (minus dominance) was a key mating type or sex determinant in volvocine algae. The Mid ortholog in unicellular Chlamydomonas (an isogamous species) specifies minus mating-type differentiation, while the Volvox Mid ortholog specifies spermatogenesis; but the Chlamydomonas MID gene was non-functional when expressed in Volvox. These results suggested to us that the spermatogenic function of Mid might have coevolved with sexual dimorphism. In our newly published study we expanded our cross-species complementation experiments and found that MID genes from two relatives of Volvox which are more closely related to it than Chlamydomonas—isogamous Gonium pectorale and anisogamous Pleodorina starrii—could both induce spermatogenesis in Volvox. The discovery that Mid from an isogamous species could function in Volvox spermatogenesis was unexpected and has forced us to rethink our model for the role of Mid and the Mid pathway in sex determination.

 

Wild-type mature female and male V. carteri sexual spheroids, from Fig. 2 in the paper

 

Since Mid proteins did not drive the transition to oogamy in volvocine algae, do you have any idea about which factors/genetic changes did?

SG&JU We are pretty sure that the number of Mid-controlled genes in Volvox has expanded substantially compared with Chlamydomonas and other isogamous genera, which makes sense because spermatogenesis involves the deployment of developmental programs that have no direct analogs in isogamous species. If Mid itself did not change substantially in the transition from isogamy to anisogamy/oogamy, then perhaps its hypothetical partner protein(s) changed to enable more target genes to be controlled. Alternatively, if a few key developmental TFs from Volvox gained Mid binding sites in their promoters, then perhaps those cis-regulatory changes were sufficient to indirectly expand the Mid network without requiring any major changes in Mid DNA binding specificity or changes its partner protein(s). We are now actively pursuing the identity of Mid target genes and Mid interacting proteins to get at this question.

 

What does your work suggest about evolutionary divergence of transcription factors following species divergence?

SG & JU This is an interesting topic that prompts some thought about the concept of homology and origins of phenotypic novelties. For Pax6/Eyeless the proteins from flies and vertebrates retained a high degree of sequence similarity and functional interactions, perhaps because they evolved as parts of a regulatory module for specifying eyes that was already highly constrained in their common ancestor and/or predisposed to evolve via downstream interactions, just as we think the Mid network did in volvocine algae. On the other hand, a small number of changes in the conserved plant TF Leafy was sufficient for neofunctionalization by altering its DNA binding site. In the case of Mid proteins in volvocine algae they are much faster evolving than Pax6/Eyeless or Leafy, so we were expecting that there might have been a major change in Mid function associated with the transition from isogamy to anisogamy/oogamy, but clearly Mid was not the major locus of change for the emergence and elaboration of this novel trait. Determining whether there are any patterns and rules for TF network evolution is still a major challenge.

 

Results of GpMID expression in V. carteri females, from Fig. 3 in the paper

 

When doing the research, did you have any particular result or eureka moment that has stuck with you?

SG Yes. I was intrigued to see that the induced female Volvox with a Gonium MID transgene produced sperm packets under microscope. Then I asked Dr. Umen to come over to check the culture on the slide. I noticed Dr. Umen was excited, but he was obviously not so sure with the result. Then we decided to do more experiments to confirm the finding. The lesson I learned here is to do more scientific analysis and experiments to make the data more convincing when unexpected results come up.

 

And what about the flipside: any moments of frustration or despair?

SG Frustration is always around when we are doing science, sometimes big, sometimes small. Transforming Volvox requires a lot of time and planning, and I felt frustrated when the transformation efficiency for Volvox was not ideal. When this occurred, I had to spend some time to figure out what’s the problem from the setting of the gene gun to the materials and reagents I used in the lab. I’m happy everything went well finally.

 

What next for you Sa?

SG My interest is still on the regulation mechanism of sex determination in volvocine algae. I will focus on the sex determination function of the Mid protein in Volvox and on the Mid network.

 

Phenotypes of Volvox female GpMID transformants, from Fig. S8 in the paper

 

Where will this work take the Umen lab?

JU Some important new directions have emerged from our study. We think the Mid network expanded during the transition to oogamy in Volvox, but we don’t know how. We want to determine whether Mid binds DNA on its own or with other proteins, what are its target genes in different volvocine species, and how did its new targets get recruited during the transition to anisogamy and oogamy. On a more general level we are asking the question of how TF networks expand and integrate new inputs and developmental processes as they evolve more complex functions.

 

Finally, let’s move outside the lab – what do you like to do in your spare time?

JU My favorite hobbies outside of the lab are food (cooking and eating), tennis and fly fishing, plus anything else that gets me into the outdoors/nature.

SG I usually take care of my vegetable garden when I don’t need to go to lab to see my algae. I play table tennis with my wife almost every day, and I also go to fitness centre quite often recently.


Evolutionary divergence of the sex-determining gene MID uncoupled from the transition to anisogamy in volvocine algaeSa Geng, Ayano Miyagi, James G. Umen
Development 2018 145: dev162537 doi: 10.1242/dev.162537

This is #40 in our interview series. Browse the archive here

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PhD position: Chromosome Dynamics During Spermatogenesis in Drosophila, University of Zurich, Switzerland

Posted by , on 19 April 2018

Closing Date: 15 March 2021

We seek candidates interested in completing a PhD thesis within the framework of a research project (46 months) funded by the Swiss National Science Foundation (SNF).

Chromosome reorganization during spermatogenesis is dramatic. Beyond meiosis, it includes chromosome compaction into an elongated sperm nucleus which is accompanied by an almost complete exchange of histones with sperm nuclear basic proteins (SNBPs). Exploiting advantages of the model organism Drosophila melanogaster, our project addresses: (1.) Homolog pairing and chromosome territory formation in spermatocytes and its molecular basis. (2.) Molecular mechanisms maintaining homolog conjunction until metaphase I, as well as Separase-dependent resolution of this conjunction just before anaphase I. (3.) Transformation of the spherical postmeiotic spermatid nucleus into the compact needle shape present in mature sperm. A wide range of methods will be applied (genetics: classic, RNAi, CRISPR/cas, proteomics, time lapse imaging, FISH, immunofluorescence).

Prerequisite for the PhD position is a MSc degree (or equivalent) in biology, biochemistry or related fields. We are looking for a highly motivated individual with a strong background in cell biology, developmental biology, molecular biology, genetics, biochemistry. Experience with Drosophila is beneficial. Successful candidates will join the PhD program in Molecular Life Sciences (MLS) of the Life Science Zurich Graduate School (LSZGS) jointly organized by ETH and University of Zurich (UZH). UZH is an equal opportunity employer.

Application deadline is 31 May 2018. Application documents should include a motivation letter, curriculum vitae and a grade transcript. Applications should be sent electronically as one single file in PDF format to the address below. Additionally, candidates should organize that two to three letters of recommendation are sent to the same address.

Prof. Dr. Christian Lehner, Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. christian.lehner[at]imls.uzh.ch

Additional information: www.imls.uzh.ch/en/research/Lehner.html

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postdoctoral fellow position: Hedgehog control of neuronal activity.

Posted by , on 19 April 2018

Closing Date: 15 March 2021

We invite applications for a postdoctoral position to join a multidisciplinary project in the Alenius group at Umeå university. The project is based on our recent discovery that Hedgehog control neuronal activity in both Drosophila and mouse1. 2  The approach is to combine Drosophila genetics, biochemistry with imaging in order to investigate the fundamental mechanisms that control neuronal activity and communication.

We are now looking for a highly motivated candidate, with a strong background in either Drosophila molecular biology or cell signalling. Additional skills in Drosophila neuroscience, imaging, and cryo-EM are considered a plus. The position involves using Drosophila genomic tools, biochemistry and live cell imaging, which in combination with cryo-EM and super-resolution microscopy and cutting-edge neuroscience approaches to identify the mechanisms by which hedgehog regulate neuronal activity.

Candidates are encouraged to send applications (cover letter, CV, and contact information of 3 references) to mattias.alenius@umu.se. Recommended application deadline is May 15th, 2018. Application review will start immediately until the position is filled. Openings are available immediately and the position is funded until the end of 2020.

Umeå and the Department of molecular biology: Umeå is a very metropolitan city with an international, welcoming and open attitude. The university and the department of molecular biology has a long standing tradition of big discoveries and is the birth place of the CRISPR/Cas9 technology. The university has several highly advanced technical platforms, including imaging and correlative electron microscopy platforms. The Department is creative, interdisciplinary and cutting edge and you will be part of one of the strongest Drosophila research environments in Sweden.

 

  1. 1. Hedgehog signaling regulates ciliary localization of mouse odorant receptors. PNAS, Kumar Maruya D., Bohm S. and Alenius M. 2017
  2. Hedgehog signaling regulates the ciliary transport of odorant receptors in Drosophila. Cell Reports, Sanchez G. M., Alkhori L., Hatano E., Schultz S. W., Kuzhandaivel A., Jafari S., Granseth B., and Alenius M. 2016

Group page: (http://www.molbiol.umu.se/english/research/researchers/mattias-alenius/)

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A better bar

Posted by , on 18 April 2018

After leaving the bar, what are we to do? I propose to move on to a better bar (and I hope that you will not be disappointed when you find out that I’m actually referring to an interval).

In a previous blog I advocated the transparent presentation and reporting of data in graphs. It was highlighted that 95% confidence intervals (95%CI) are the preferred indicator of uncertainty (Gardner and Altman, 1986; Cumming 2013).The 95%CI of the median can be indicated by notches in boxplots (Krzywinski and Altman, 2014). The calculation of this 95%CI is based on the interquartile range (McGill et al., 1978). However, this definition does not allow for asymmetric confidence intervals and may therefore not be ideal when samples sizes are moderate and distributions are non-normal or skewed. Here, I will discuss another method for calculating and visualising the 95%CI for the median, which is based on bootstrapping. The analysis and visualization is done using the open source software environment R & ggplot2 and the scripts are available here.

 

Asymmetry & the median

In our work, the distribution of measured values rarely adheres to a normal distribution. Skewed, or asymmetric distributions are commonly encountered. It has been put forward that the normal (or Gaussian) distribution is the exception rather than the norm (Wilcox, 2017). Moreover, when sample sizes are small, it is virtually impossible to determine whether it adheres to normality. In case of asymmetric distributions, the median is better measure of centrality (i.e. the typical or representative value of a sample) than the mean (Wilcox and Rousselet, 2017). As a consequence, it makes more sense to display medians instead of means when experimental data is visualised (footnote 1).

 

Bootstrap & the median

The bootstrap is a computational method that generates a large number of samples based on the existing experimental sample, instead of performing additional measurements (footnote 2). The bootstrap approach is a robust and versatile method that was introduced and popularized by Efron and colleagues (Efron, 1979; Efron and Tibshirani, 1986). It has been demonstrated to work (surprisingly) well. Its main powerful feature is that it can be used to derive statistics that are impossible to calculate directly. More details on bootstrapping can be found here and here). A brief description of the procedure follows. Suppose you have done a measurement and obtained a sample of 20 values. A random value is drawn from this experimental sample, and this is done 19 more times, to obtain a bootstrap sample (footnote 3). This procedure of resampling can be performed multiple times (usually somewhere between 1,000 and 10,000 times). The statistic of interest can be determined from each of the bootstrap samples. Figure 1 illustrates the bootstrap process for resampling the median 1000x (an animated version is available here).

Figure 1: The principle of bootstrapping. The original data (left panel) is resampled to generate a bootstrap sample and the median is determined. This process is repeated many times (1000x in this example) to generate a collection of new median values. The median of the sample is indicated by the horizontal line and this new value is added to the collection of medians (indicated with the large dot). An animated version of this figure as well as R scripts to generate these figures are available.

 

Confidence & the median

The 95%CI is supposed to capture the statistic of interest 95% of the time, if the sampling was repeated multiple times. Repeated sampling is exactly what the bootstrap procedure is all about. Therefore, we can use the bootstrapped samples of the median to derive the 95%CI of the median (Wood, 2004). To this end, we rank the 1000 median values that were obtained by resampling from low to high. The 95%CI is now defined by the middle 95% of these values (footnote 4). In case of 1000 bootstrapped samples we use the 25th value and the 975th value of the ranked medians as the limits of the confidence interval. Figure 2 shows the histogram of the sampling distributions and the limits of the 95%CI as vertical lines.

 

Figure 2: The distribution of 1000 median values obtained by bootstrapping (same data as used in figure 1). The vertical lines indicate the limits of the 95% confidence interval [0.74, 0.81].

 

 

Let’s get back to where it all started, i.e. better bars intervals. As an example I compare the data shown in a previous blog with the 95%CI determined as for boxplot notches and the 95%CI calculated by the percentile bootstrap (figure 3). The medians and the confidence intervals are shown below as grey bars (the raw data is left out of the plot to draw attention to the 95%CIs). The main difference between the two methods is the asymmetry of the confidence interval that was determined by bootstrapping which better reflects the underlying data.

Figure 3: Comparison of the 95% confidence interval (indicated with a grey bar) as defined for boxplot notches (left) and determined by boostrapping (right). An R script to produce this figure is available here.

 

Final Words

The percentile bootstrap method for calculating confidence intervals for the median is “not bad”, but improved bootstrap methods are described (Hesterberg, 2015). There is also another way to determine a 95%CI of the median based on work by Hettmansperger and Sheather which is implemented in R (Wilcox and Rousselet, 2017).

Which of the methods for calculating the 95%CI works best for your data needs to be judged on a case-by-case basis. Only if the distribution of the population values is known, the best 95%CI can be identified by performing simulations. However, since the properties of the population distribution are usually unknown, a firm conclusion on the most accurate 95%CI is not possible. To conclude, I like the percentile bootstrap method for calculation of the 95%CI for the median since it is relatively accurate, intuitive and it allows for asymmetric intervals.

 

Shout-outs to:

Peter Kamerman for the code on his blog that was used to calculate the 95%CI by bootstrap: https://www.painblogr.org/2017-10-18-purrring-through-bootstraps.

Guillaume Rousselet for explaining the basics of robust methods and for sharing his insights on robust statistics in numerous blogs.

Marten Postma for introducing me to bootstrap methods.

 

Footnotes

Footnote 1: The median is not a cure-all and has some issues of its own. Another robust measure of centrality for non-gaussian distributions is the trimmed mean. The accompanying R scripts can be modified to determine the 95%CI of a trimmed mean via the percentile bootstrap.

Footnote 2: To experimentalists, the bootstrap approach may seem like cheating. It is important to realize that the bootstrap method does not increase the number of datapoints. Instead, it is based on the concept that the existing sample represents the population and therefore can be resampled to obtain new samples that also represent the population that was originally sampled.

Footnote 3: In bootstrapping the resampling is performed with replacement, which means that the same value can be drawn multiple times.

Footnote 4: Since the confidence interval is based on the middle 95% of the distribution and the limits of the interval are based on ‘percentiles’ this procedure is also known as the percentile bootstrap.

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Postdoctoral and PhD position in Drosophila developmental biology

Posted by , on 18 April 2018

Closing Date: 15 March 2021

Laboratory: Laboratory of developmental biology, dr. Alena Krejci, Biology Centre, Czech Academy of Sciences, Ceske Budejovice, Czech republic

http://www.prf.jcu.cz/en/kmb/research/research-groups/laboratory-of-developmental-biology.html

We aim to dissect the interplay between metabolism and major signalling pathways, with the emphasis on Notch signalling pathway.

 

Project: Metabolic stress as regulator of Notch signalling

The Notch pathway has been described in several contexts to regulate glycolytic as well as mitochondrial metabolism (including paper from our lab Slaninova V, Open Biology, 2016). At the same time, recent evidence suggest that Notch pathway activity is sensitive to the cell metabolic parameters, such as the NAD:NADH ratio, amino acid availability or activity of metabolism related signalling pathway such as mTOR (Horvath M, Biochem J, 2016 and our current paper in preparation). We investigate this interplay using Drosophila wing disc, eye disc and immune system as models. The theme of the postdoc/PhD project will be directed to identification of binding sites for a previsouly unknown Notch targeted transcription factor that mediates crosstalk between Notch signalling, metabolism and immunity.

Applicant: Applicant should have a degree in molecular or cellular biology. Previous experience with Drosophila, molecular biology techniques and/or confocal microscopy is welcome.

Position: Postdoc offer includes a fixed contract till end of 2019 with the possibility of extension. PhD position is a part of the 4-year PhD program at the Department of molecular biology and genetics, University of South Bohemia. More details of the Department at http://www.prf.jcu.cz/en/kmb

Send your CV including address of two referees to akrejci@prf.jcu.cz

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Daniyal Jafree winner of the BSDB advocacy writing competition

Posted by , on 17 April 2018

BSDBlogo
In preparation of the 70th anniversary celebrations at the special Spring Meeting in Warwick (15-18 April 2018), the student and postdoc representatives of the BSDB, Alexandra Ashcroft and Michelle Ware, initiated a writing competition for graduate student and postdoc members who were asked to write a max 500 word piece on one of the following topics:

  • The future of Developmental Biology
  • What Developmental Biology has contributed to society
  • The experiment/paper in Developmental Biology that most inspired you

12 excellent submission entered the competition and were judged by Katherine Brown, Aidan Maartens, Ottoline Leyser and Jonathan Slack. The first prize, a free trip to and attendance of the 77th Annual Society of Developmental Biology meeting (Portland, Oregon, USA) was announced at the Spring Meeting’s conference dinner. The BSDB would like to congratulate the winner Daniyal Jafree (@daniyal_jafree). Please, read below and let yourself inspire by the submissions we received.

 

The winner Daniyal Jafree is a medical 1st year PhD student working on the project “Unravelling the origins of the kidney lymphatics” in the group of Dr David Long at UCL. In his piece he writes about a paper by Paul Riley from 2015 which addresses the development and function of the cardiac lymphatic system. Danyial’s piece is a wonderful example of how good DB research has induced a paradigm shift in the cardiac field, but also profoundly changed the career of a young researcher. As Danyial writes at the end: This paper inspired me so much that I contacted Professor Riley to ask whether he had any free positions in this lab. Sadly, he didn’t. But, funnily enough, I am now tackling a PhD in lymphatic biology at my own university, integrated into my medical degree. And guess who I’m collaborating with!

Laura Hankins (runner up; Dunn school, Oxford) relates childhood memories of observing newts at the pond with the transplantation experiments performed in newts by Hilde Mangold and Hans Spemann – the experiments that sparked Laura’s interest in Dev Biol. She reminds us of the fact that our science is more than the focus on disease and sustainability, but concerns true biology and the wonders of nature around us. And she alerts our technology-focussed minds to the fact that there is an art and beauty in experimental design whatever method we use. As Laura comments towards the end: “This experiment is inspiring partly due to the minimalism of its approach; it demonstrates that the most influential experiments are designed without unnecessary embellishment.

Victoria Rook (runner up; PhD at Queen Mary, London) takes a very different, critical view at the future, elegantly framed by comparing current developments in cloning and the use of chimerae and genomic engineering to the dystopian science fiction book “Oryx and Crake” by Margaret Atwood. Weighing optimism against pessimism, she ends with the words: “Soon we will have the resources to cure numerous genetic diseases and, in theory, the ability to improve the lives and health of generations to come. The unease comes with how far we are liable to take this, is a dystopian future where ‘pigoons’ and ‘crakers’ run wild within our reach, or will they remain a thing of fiction?

See also a selection further submissions:

Kane Toh Qin uses Conrad Waddington epigenetic landscape proposed in the 1940s as an example to project from the past to the presence and beyond.

Emilio Mendez describes how learning about limb bud transplantation experiments performed by Ross G. Harrison in the 1920 inspired his passion for Developmental Biology.

Amanda Berg looks at the future of humans in space and the colonisation of other planets, and the need to investigate the possibility of reproduction and embryonic development away from earth.

Caitlin McQueen describes how she was influenced by the publications on nuclear transfer experiments carried out by John Gurdon in Xenopus laevis intestinal cells.

Massimo Ganassi talks about the difficulty and importance of communicating our science.

Anna Klucnika alerts to the need of communicating DB and provides some thoughts how to do it.

Sandra G González Malagon asks the fundamental question of what DB has contributed to society.

 

Essay question: The experiment/paper in Developmental Biology that most inspired you (winner)

Daniyal Jafree

As a medical student into Developmental Biology, it bugged me when my friends asked: “Why Developmental Biology? That’s boring, and not relevant to medicine at all?” For me, there is no paper that disproves this greater than that published by Paul Riley and colleagues from the University of Oxford, in Nature in June 20151. This paper, representing eight years of work, examined the development and function of the cardiac lymphatics. Together with two other papers published at around the same period, Riley and his group overturned a 100-year old dogma in lymphatic biology within the space of about 12 months, and laid the foundation for a new therapeutic strategy for heart disease.

Lymphatic biology is a very hot topic. These vessels, at the interface between vascular and immune systems, have been implicated in cancer, obesity, hypertension, inflammatory diseases and beyond. Lymphatics supposedly arise from a single source. A subset of cells in the wall of the cardinal vein express markers of lymphatic fate specification early in development. These cells bud off, form lymphatic sacs, and reach out to produce the entire lymphatic system. At least that is what we thought.

Riley and his group performed Cre-based lineage tracing to capture the venous-derived lymphatics in the heart. Remarkably, not all of the cardiac lymphatics were labelled. So where on earth were these non-venous derived cells coming from? The group went ‘all out’, using a battery of Cre lines in a painstaking effort to capture these mysterious cells. The answer was shocking: they were not coming from the heart, nor the embryo at all! They were coming from outside the embryo, from haemogenic endothelium in the primitive yolk sac. That yellowish bag-looking thing that I always dissected and disregarded when doing my own experiments.

But Riley and his group didn’t stop there. Given the importance of the lymphatics in fluid homeostasis and inflammation, they were reasoned to have a role in cardiovascular disease, one of the biggest killers in the modern world. The team took lymphatic reporter mice and induced cardiac injury, by tying off a key artery supplying the myocardium. Lymphatic vessels expanded, and this growth occurs via the same programmes that drive lymphatic expansion in development. Using magnetic resonance imaging (which, as a medical student, I had no idea was possible in mice), they showed that treatment with a lymphangiogenic growth factor improved heart function after cardiac injury.

This paper isn’t my favourite solely because it challenged an age-old hypothesis, and did so robustly by using multiple parallel experimental strategies. It’s also the link it makes to a common disease process, and the manipulation the same programmes that drive lymphatic development to halt this process. This paper inspired me so much that I contacted Professor Riley to ask whether he had any free positions in this lab. Sadly, he didn’t. But, funnily enough, I am now tackling a PhD in lymphatic biology at my own university, integrated into my medical degree. And guess who I’m collaborating with!

References

  • Klotz et al. (2015). Cardiac lymphatics are heterogeneous in origin and respond to injury. Nature, 522: 62-67.

Daniyal’s acceptance speech:

“I’m grateful to be receiving this prize from the BSDB, and I’m actually baffled I won, considering I’ve never had any formal teaching in developmental biology. I’m a medical student with no clear indication as to what clinical specialty I want to pursue, but with a strong interest in developmental biology. Unfortunately, I think I’m in the minority. I have lost count of the number of times that non-basic science-trained clinicians ask me about my interests, and when I respond, their faces screw up as if they have taken a large bite from a lemon.

Through my clinical career so far, I’ve always found myself coming back to developmental biology, with the support of the BSDB. First, as part of an integrated BSc degree during medical school, after which the BSDB supported my attendance at a conference in Chicago. Later in 2016, as part of a BSDB-funded summer studentship. And now, being supported by my medical school to do a PhD in lymphatic development, alongside my medical studies.

I think there is so much the clinical world has to learn from developmental biology, about birth defects, cancer, regenerative medicine and beyond. The paper I wrote about in my essay is just one incredible example of developmental biology’s potential. This paper, published in Nature by Paul Riley’s group in Oxford, showed that cardiac lymphatics develop in a completely unexpected way and, with two other papers published the same year, overturned a 100-year old dogma in lymphatic development. Riley and colleagues went on to show that tinkering with the same pathways that drive lymph vessel growth in development, can be used to manipulate lymph vessel growth to benefit cardiovascular disease. This is why it is undoubtedly my favourite scientific paper, since its publication in 2015.

I really hope, one day, I can forge a career that brings the clinical world and developmental biology closer together. So thanks to the BSDB and the massive support it’s provided me over the years, as you have given me hope that such a career can, and will, happen. And, of course, thank you again for this amazing prize.”

Painting the embryo by numbers: how nature provided the tools for an inspirational experiment (runner up)

Laura Hankins

Visit a local pond and lie flat on your stomach, allowing the soft mud to seep into your clothes. Be sure to bring a jam jar; it will sparkle in the lazy spring sunlight as you shift it closer to the water’s edge. Wait patiently, observing any disturbances to the dappled surface. There! The flat tail of a newt in the breeding season.

Pleurodelinae is an unassuming collection of newt species within the Salamander family. As a child, sitting by the pond in our front garden, I was often charmed by the sedate movements of common newts contrasting with the constant hum of traffic whipping past. I think I probably wanted to hunt for new species in undiscovered rainforests, as this seemed a reasonable career move at the time. Little did I know that the humble newt would reappear in a university lecture, starring in an experiment that inspired me to pursue Cell and Developmental Biology.

It is 1924. In Hans Spemann’s laboratory, our friends the newts have been the subject of a series of experiments performed by Hilde Mangold as part of her doctoral studies. Spemann was no stranger to amphibians; his work on eye development had made good use of frogs. Now he had turned his attention to how broader embryonic regions are defined.

During gastrulation, the embryo folds in on itself to produce three distinct layers that will ultimately have different fates. This produces the blastopore, an opening that acts like an insatiable mouth as the embryo consumes itself. Spemann, amongst others, had observed that transplanting tissue from the blastopore lip into another embryo resulted in the formation of a second neural tube and its surrounding structures. Many assumed that these features arose exclusively from the donor cells, but Spemann and others hypothesised that these cells could be acting as an ‘organiser’, signaling to influence their neighbours’ fates. But how to test this suggestion?

The breakthrough came with an idea that was beautiful in its simplicity. Mangold repeated the transplantation experiments but moved the tissue between different newt species. These newts had distinct pigmentations, so it would be possible to discern host from donor tissue after leaving the embryo to develop following surgery. In 1924, embryos left for sufficient time developed a chimeric conjoined twin with its own neural tube, notochord and somites. After sectioning, Mangold observed that these structures contained both pigmented and unpigmented cells. Remarkably, it seemed Spemann was right: the transplanted tissue had somehow altered the fate of the surrounding host cells, coopting them into forming an artificial twin.

This experiment is inspiring partly due to the minimalism of its approach; it demonstrates that the most influential experiments are designed without unnecessary embellishment. Yet its surgical element made it incredibly technically complicated. Thanks to their logical design, and the natural features of newts, Spemann and Mangold changed our perception of cell fate determination. Years later, researchers are still being inspired to use knowledge of the natural world to address questions at the cellular level.

Is the future of developmental biology written in science fiction? (runner up)

Victoria Rook

As a developmental biologist and devoted reader of dystopian science fiction, I frequently wonder how often these two things overlap, when will fiction become fact and fact mirror fiction? A couple of years ago I came across a fantastic book, Margaret Atwood’s Oryx and Crake 1. This book is set in a desolate, dystopian future that arose as a consequence of biotechnology corporations taking genetic engineering to extremes. The accountable corporations created many chimeric animals, one magnificently named example are the ‘pigoons’;

The goal of the pigoon project was to grow an assortment of fool-proof human

tissue organs in a transgenic knockout pig host….1

In January 2017, Juan Carlos Izpisua Belmonte at the SALK institute, California, published a paper in Cell titled; Interspecies chimerism with human pluripotent stem cells2. In this article, Belmonte introduced human stem cells into pre-implantation pig embryos. Chimeric human-pig embryos were then implanted into female pig recipients and developed for four weeks before analysis. The ultimate objective of this research is to grow replacement organs in pigs for human transplant. Unfortunately, Belmonte did not credit Atwood for her conceptual influence and, more disappointingly, there is no mention of ‘pigoons’ throughout the paper.

Atwood also describes a superior human species, the ‘crakers’, which were developed as prototypes of what could be available to those willing to pay top dollar for ‘genetically perfect’ children. A decade later, Feng Zhang’s group in Harvard were the first to report CRISPR-Cas9 mediated genome editing3. Shortly after, in 2015, Junjiu Huang’s group in China used this CRISPR-Cas9 technology to carry out targeted genome editing in human embryos4 with the intent to treat β-thalassemia. More recently, Kathy Niakan, a group leader at the Francis Crick Institute in London, has obtained a HFEA license to use CRISPR-Cas9 technology to manipulate the human embryo genome in order to study early development. Understandably none of these embryos have been, or will be implanted into human recipients, but how far away are we from being able to create Atwood’s ‘crakers’?

Oryx and Crake is one prophetic example where fiction has seemingly ‘foretold the future’, posing questions about how much can we learn about the future of developmental biology from science fiction? Aristotle showed us model organisms could be used to study development, however, given innovations in CRISPR-Cas9 technology and ongoing discoveries of evolutionary developmental differences between species, is it likely that model organisms will become a thing of the past and CRISPR-engineered human embryos pave the way of the future? Whilst this may sound like a pessimistic prognosis for the future of developmental biologists working with model organisms, I am actually very excited for what the future holds. Soon we will have the resources to cure numerous genetic diseases and, in theory, the ability to improve the lives and health of generations to come. The unease comes with how far are we liable to take this, is a dystopian future where ‘pigoons’ and ‘crakers’ run wild within our reach, or will they remain a thing of fiction?

References

  1. Atwood, M. Oryx and Crake. (Bloomsbury, 2003).
  2. Wu, J. et al. Interspecies Chimerism with Mammalian Pluripotent Stem Cells. Cell 168, 473–486.e15 (2017).
  3. Cong, L. et al. Multiplex genome engineering using CRISPR/Cas systems. Science (80-. ). 339, 819–824 (2013).
  4. Liang, P. et al. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell 6, 363–372 (2015).

Does developmental biology have a future?

Anna Klucnika

Last year I marched the streets of London with thousands of other science enthusiasts, as many more thousands did so in other cities across the globe. The reason? Politics has gotten in the way of science and the public is, apparently, tired of experts.

With funding plummeting in the UK and already slashed in the US, the future of research is unclear. There is increasing pressure from the public, funding bodies and governments for biological research to focus on questions that generate click-bait headlines claiming a disease cause or cure. Research with direct applications for human health and disease is unequivocally important. However, recent funding trends reveal that basic biological research is being institutionally neglected. This will leave huge collections of questions unanswered. Many of these questions would have lead onto findings with broad implications that could have revolutionised human health.

Developmental biology is one such science that is often perceived to have little implication on the lives of the majority of the population. Developmental biology is the study of how cells make tissues, organs and organisms. This humble field has led to many discoveries with worldwide impact, for instance cloning, understanding birth defects and optimising IVF. Nevertheless, developmental biology is persistently undervalued. Research using animals that are more commonly known as pests was always going to be a hard sell.

In walks Developmental Biology’s sexier cousin: stem cell and organoid biology. Really, these two scientific fields are more likely sisters. Both ask the same question (how do cells make organs), but stem cell and organoid biology inherently has more of a focus on research with direct therapeutic applications. Organoids can be used to aid our understanding of organ growth and tumorigenesis, to screen for drugs and may potentially enable us to grow organs for transplantation and so is attractive to funders and, crucially, the public.

To grab the public’s attention, Developmental Biologists need to learn from the organoid field and showcase the research that has fast-track therapeutic potential. Old school developmental biologists whose careers blossomed when curiosity-driven science was enough will be severely offended by this statement. But scientific culture has dramatically changed. We are in an era of information overloaded in which headlines are updated every minute, not day. Sexy science thrives in this environment, whilst the less-glamorous fields are quickly forgotten.

To stay in the game, Developmental Biology needs a makeover. We need a new vocabulary that everyone can understand. We need to be proud of the research that will have an impact on the public’s life. Most importantly, we need to be united in our goal. Developmental biology is an extremely broad term. We must not be eager to divide ourselves based on our research, our question or our model. Ultimately we are all trying to work out the mystery of how a single cell can make something as amazing as a plant or animal. Once we remember that, we can share the sex appeal and developmental biology can thrive. Maybe we can convince people that experts aren’t so bad after all.

The future of Developmental Biology – addressing biological complexity

Kane Toh Qin

Conrad Waddington proposed the metaphorical epigenetic landscape in the 1940s as a model for the unfolding of discrete cell fates. In the modern post-genomic era, the metaphor has experienced a resurgence in popularity. Tailored with the theory of dynamical systems, developmental biologists have used the conceptual apparatus to make quantitative predictions of differentiation dynamics. The appeal of the epigenetic landscape illustrates the importance of conceptual frameworks in developmental biology to highlight general principles of development; a notion that is especially pertinent in light of the overwhelming complexity of the ‘omics’ datasets today.

As sequencing technologies, time-lapse imaging techniques and genetic engineering methods continue to improve, we will have the technical tools to probe the epigenetic landscape. I believe that Developmental Biology in the future will provide increasingly coherent and precise explanatory accounts of phenomenological discontinuities that arise in different spatial and temporal scales of organismal development. For instance, how do fluctuations in the number of mRNA and proteins in a single cell allow for the coordination of cellular decisions over cell populations? How is the genotype-to-phenotype map implemented in an organism, and how do these properties influence its long-term evolutionary dynamics and vice versa?

To pave the way for these explanations, developmental biologists should further appreciate that knowledge of the component parts of biological systems alone will not beget knowledge of principles of development. As the complex systems biologist Kunihiko Kaneko argues, using an analogy from physics, without the existence of (macroscopic) thermodynamics, statistical mechanics, which connects microscopic behaviour to macroscopic thermodynamic quantities, would not have existed as a branch in physics. This will encourage a shift in perspective away from a reductionistic snapshot of biological components to a processual, dynamic framework of developmental mechanisms as coupled, interacting processes in complex systems. As the physicist Robert Laughlin puts it affectionately, life is the ‘granddaddy of emergent phenomena’ and emergent phenomena, as we know it, arise from a collection of interactions.

The complexity of living systems is such that further progress in Developmental Biology will inevitably require advances that derive from interdisciplinary dialogues between natural scientists. As such, developmental biologists will become more familiar with the tools and concepts involved in constructing quantitative explanations to complement their study of developmental mechanisms. For example, information theoretic measures like entropy are used today by some biologists to understand the process of stem cell differentiation at a single cell level.

With the accumulation of so much biological data, one can sympathize with the notion that the complexity of biological development eludes further human understanding—a position that spurred the embryologist, Hans Driesch to embrace vitalism. But we should be optimistic about the future: organismal development can be understood mechanistically, by first extracting its most important features and then analysing the patterns that emerge with the interdisciplinary tools and conceptual frameworks at our disposal. The principal task of developmental biologists then is to continue directing attention to the Biology and working out the crucial biological features for investigation.

The experiment/paper in Developmental Biology that most inspired you

Emilio Mendez

My history is funny I think. When I was a kid, I remember asking my father about why elephants were so big? Why mice so small? Why our Pomeranian dog was small? Meanwhile, our neighbour had a big German Shepherd. My father was intrigued by my questions and decided to bring a complete juvenile encyclopaedia and tried to find the answers I was looking for inside it.

Those questions usually disappear quickly with traditional education, puberty, football and love. My father past away when I was sixteen years old, however, he left me many teachings about life, he always told me two things, first, try to understand what you cannot explain, usually its worth. Second, what a man can build, another one also can.

When I had to choose my path after high school, I decided to study Biochemistry, because I like it a lot biology and chemistry. However I was not familiarised with the work of a scientist, for me it was more like “I like that, and I do not like mathematics”, however, I have never been so wrong. Soon I got in touch with that other science, and my mind was amazed at the fact that they are interconnected in such a beautiful way that it is childish to think they walk separated ways in build our world.

When I was finishing my career, I decided to take a course called “Genetic Control of Development”, totally unaware of what it was about, but what I found was love at first sight. Suddenly all my questions, my early questions came to my mind, especially when I saw the paper of Ross G. Harrison 1924, he transplanted limb buds of two different species of salamanders, with the idea of study which factors or signals affect the proportions of tissues. As the title of the paper, unexpectedly, both limb buds developed to its average size (donor size). That shocking difference was all I was looking for; suddenly I realise my question about the size of an individual it has no answer yet, however many factors have been described since Harrison (and Twitty 1931).

Those papers are essential for me because they summarise the beauty of Developmental Biology, simple question with simple experiments and a fantastic result, which open new roads to explore how the life has developed in our world. Later on, during my PhD studies, I meet the magnificent book “On Growth and Form”, it is the perfect crystal of all the sciences working together to build a life. I believe that if every boy and girl could see this book, many of them will never lose their curiosity about our world.

These are some of the elements that guide me to developmental biology, they drive me back to my childhood, like an old forgotten melody that came up out of nowhere. Just to realise how brave my father was.

I think he was telling me to study what a man cannot build yet, the life.

The future of Developmental Biology

Amanda BergAs the human species expands its curiosity and desire to explore the unknown, the concept of inhabiting other planets does not seem too distant. As humans, we are naturally curious and have always had the desire to explore our surroundings. Colonisation of Mars, or even more distant planets, will rely heavily on the successful reproduction and growth of the human species. Currently, scientists are investigating the physiological role that gravity and space travel can play on our bodies, but for successful fertilisation and growth of foetuses in space, we will also need to start thinking about the effect of space flight and gravity on a developing embryo.

Xenopus laevis embryos have previously been sent to space and as a result they grew into abnormally developed larvae. They had longer tails, combined with smaller heads and bodies than the Earth-grounded comparisons. Their notochords were deformed, with resulting abnormal curvature of the spine, causing them to swim in backwards somersaults (Snetkova et al., 1995). It is possible that these defects are due to abnormal dorsal-ventral axis specification which is determined through cortical rotation, and is thought to rely on gravity.
Another experiment was also proposed to attempt to grow chicken embryos in space, but due to the complicated experimental design and short time-scale given to the project, it never went ahead (NASA, 1977).

More recently, 2-cell mouse embryos were sent into space, which went on to develop into healthy blastocysts (Chinese Academy of Sciences, 2016). This exciting result means human embryos may also be able to develop in space. It would be exciting to investigate whether these blastocysts could be implanted into female mice, and whether they can form healthy offspring.

We will also need to consider whether normal reproduction can occur in space. Fertilisation had occurred on earth for all of these experiments, and the animals were also not grown to full term. We will also need to consider the different gravitational fields found on other planets; how would an embryo look if it was conceived and fully developed on the International Space Station, where gravity is almost minimal? What about on Mars, where the gravity is weaker than on Earth?

It is inevitable that humans will attempt to colonise other planets, and to do so we must investigate the possibility of reproduction and development of embryos in space. We can only hope that healthy foetuses can develop, and that the growth of the human species is not inhibited by its own developmental biology.

References:

Chinese Academy of Sciences (2016) “Chinese scientists develop mammal embryos in space for first time”, accessed 01.03.2018 [LINK]

NASA (1977) “SP-401 Skylab, Classroom in Space. Chapter 5: Embryo Development in Space”, accessed 01.02.2018 [LINK]

Snetkova, E. et al. (1995) ‘Effects of space flight on Xenopus laevis larval development’, Journal of Experimental Zoology Part A, 273(1), 21-32

What has developmental biology contributed to society?

Sandra G Gonzalez Malagon

“How are we formed?” My 6-year old nephew asked me with innocent wisdom. It’s been 17 years since and I still do not have a simple answer for him. The observation of natural life and the attempts to explain the world around us has fascinated human beings throughout our existence. Even Ancient Greeks considered fundamental questions about embryogenesis and inheritance. Developmental Biology (DB) covers all of these related questions: How do different organisms develop? What controls the patterning of different species? What are the subtle differences that lead to individual characteristics? What happens if the synchrony is disturbed? How does the environment influence an organism’s development?

Our Society today has a better understanding on how a person’s life develops from the womb. New parents can not only envision the stages of development of their unborn baby, but they also are aware of the importance of reproductive age, a healthy lifestyle and the risks of alcohol, cigarettes, medications and environment on their child’s development. They can be offered in utero diagnosis of chromosomal abnormalities or assessment of embryos prior to implantation can be a choice for parents who present high risks of passing a disease to their child. This information has made a tremendous impact not just for families, but also potentially eradicating disease and addressing global health problems.

DB studies identified the factors required for a cell to remain pluripotent -undifferentiated state- and the factors to induce these cells into specific cell types, (muscle, neurons, etc.) These findings provided the basis for the complicated protocols used to culture them in vitro. The surprising ability of these pluripotent cells to self-organise ex vivo and differentiate into a functional “organoid” (a small replication of a functional organ) has given the field of translational and basic research an outstanding advantage. These organoids can be cultured from human cells and are a great tool to model human diseases and to find personalised treatments. Stem Cell Research and Regenerative Medicine are the two emerging fields in Biology that have reshaped the way we think of development and disease. Although not yet mature, potential treatments for diabetes, neuronal regeneration, or gut repair -just to mention a few- are in the list of possible successful treatments, that up to date, have not been found.

From understanding how we develop to finding disease treatments, how other organisms develop to how the environment influences these processes and evolution, DB will continue to be the “stem cell of biology disciplines”, as Professor Scott Gilbert described in his recent essay on this topic. DB has the potential to give rise to many disciplines in biology, as it has been doing for a long time. As for my nephew, I hope that the innate developmental biologist that lives in every kid continues to be curious and astonished about the natural world that surrounds us. Only this will help preserve our planet and the species that live in it.

The Duty of Developmental Biologists

Massimo Ganassi

“So, which illness are you trying to make the cure for?” -he asked me mumbling- “Well, we are now studying how muscle is formed during embryonic development and this may be helpful to understand what goes awry in muscle diseases and therefore suggest a cure”. Even more confused he looked at me and said: “ mmm… but I guess it would be better, and quicker, to study how to cure the disease directly rather than how something is working when is working right, isn’t it?”. I admit, this always sounds a very honest, genuine and reasonable suggestion from a “non-science” person. Indeed, at this point I usually avoid adding confusion saying that I do research on embryonic fish muscle development.Similar conversations happen frequently to me, whenever I try to explain what my job is and how scientists spend their hours working.

For everyone, from kids to older people, it is easy to appreciate the efforts of a baker, a plumber or a bus driver simply because they produce usage for everyone. In contrast, the importance of scientific research does not reach the many and Developmental Biology is still thought to be a mere scientific and academic discipline whose results are far away from everyday life needs. Sadly, this just reflects how far the “normal” and “scientific” worlds are still apart, and it is partly our fault.

From the pioneer work of D’Arcy Thompson1, through the golden decades of developmental biology, to the most recent “omics” era an incredible amount of knowledge has been reached and fruitfully contributed to our wellness. As insiders we all know that developmental biology deeply enhanced the understanding of a multiplicity of biological processes from fertilisation of egg cells to the healing of wounds, nevertheless contributing to the treatment of human conditions such as infertility, cancer or genetic diseases. Moreover, several excellent works have highlighted the central role of Developmental Biology in an attempt to attract and engage the lay public into scientific research discoveries2,3,4,5.

As a matter of fact, nowadays, communicating science is even more important than making scientific discoveries. This is also reflected by the importance given to public outreach events and their primary role even in grant proposal applications. We must convince people that basic research is worth their consideration and money donation. Recently, to help scientists in public outreach, many platforms have become available to spread science, from the more specialist web-forum The Node to the more common social media6.

We do have the responsibility and duty to translate the importance of our research by strengthening our communicative potential. This means explaining to people why animal models such as mouse, zebrafish, frog and fruitfly are so important in our research and how developmental biology has contributed to everyday life, from the most recent medicine advance to the latest agriculture technique. This has to be the main goal of every scientist. We do make daily efforts to achieve our research aims and we must make our goals and results understandable by everyone.

References

[1] Thompson D’AW. On Growth and Form. (1917) Cambridge University Press.

[2] Prokop A. What is developmental biology and why is it important. (2018) https://www.openaccessgovernment.org/developmental-biology-important/41386/

[3] Edge L. What Is the Future of Developmental Biology? (2017) Cell 170:6 -7, doi: 10.1016/j.cell.2017.06.019

[4] St Johnston D. The Renaissance of Developmental Biology. (2015) PLoS Biol 13(5): e1002149. doi:10.1371/journal.pbio.1002149

[5] Pourquié O. Development: looking to the future. (2012) Development 139: 1893-1894; doi: 10.1242/dev.082685

[6] Vicente C., Maartens A., Brown K. The Node and beyond-using social media in cell and developmental biology. (2017) Semin Cell Dev Biol. 70:90-97. doi: 10.1016/j.semcdb.2017.05.009.

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Research Position, Mokalled Lab

Posted by , on 17 April 2018

Closing Date: 15 March 2021

The Mokalled lab at Washington University School of Medicine is seeking outstanding applicants for multiple research positions (http://www.mokalledlab.com/).  Our lab uses zebrafish and mouse model systems to study neural regeneration after spinal cord injury or disease.  Candidates with enthusiasm for neuroscience, regenerative biology, and zebrafish research are encouraged to forward a cover letter, CV, and list of 3 or more references to mmokalled@wustl.edu.

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Richard Gardner is the 2018 BSDB Waddington Medal winner

Posted by , on 16 April 2018

BSDBlogoThe Waddington Medal is the only national Developmental Biology award in the UK. It honours outstanding research performance as well as services to the subject community. The medal is awarded annually at the BSDB Spring Meeting, where the recipient presents the Waddington Medal Lecture. Here we introduce the 2018 winner Richard Gardner who won the 2018 Waddington medal for his outstanding work in the field of early embryogenesis and stem cells, as well as continued contributions to the development of our field and the shaping of science policy in the UK.

 

Born in 1943,  Richard Lavenham Gardner, Kt, MA, PhD, ScD, FIAT(Hon), FRSB, FRS studied at St. Catharine’s College and the University of Cambridge from 1963-1966, graduating with a First Class Honours B.A. in Physiology. For his PhD, he remained in Cambridge in the Physiological Laboratory of Robert Edwards (Nobel prize winner, pioneer in reproductive medicine and in vitro fertilisation / IVF), where he worked alongside Martin Johnson and was awarded his title in 1971 for his thesis entitled “Investigation of the mammalian blastocyst by microsurgery”. He stayed on in Edward’s lab as a research assistant for another three years, from where he moved to a University Lecturer position at the Department of Zoology, University of Oxford (1973-77). During that time (and beyond) he was a Visiting World Health Organization Fellow in Warsaw and Zagreb and Student of Christ Church (Oxford). In 1978 he became Henry Dale Research Professor of the Royal Society at the University of Oxford until 2003. Thereafter he held positions as Edward Penley Abraham Research Professor of the Royal Society (2003-8), honorary Visiting Professor at the University of York (2007-16), and is now an Associate at the University of Oxford and Emeritus Student of Christ Church, Oxford.

Scientifically, Richard is well known as a pioneer in the study of early mammalian development, having made many hugely important discoveries relating to the fate of cells in early mammalian development and the properties of stem cells derived from early embryos (see selected papers below). These were made possible by his strong knack for identifying important questions and addressing them in innovative and at the same time definitive ways, always with extremely elegant experimental design.

His numerous important scientific contributions include: being the first to use clonal analysis to fate map the early mouse embryo, along with experimental manipulations to assess the potency of individual cells, establishing how the germ line is segregated in the early embryo, and pioneering blastocyst injection for studying stem cell potency. His work laid essential foundations for pre-implantation genetic diagnosis, now widely used in human fertility clinics, and for the embryonic stem cell (ESC) field. He was one of the pioneers developing and using micromanipulation techniques in mammalian embryos, the kind of technique now commonly used, for example for human IVF and cloning (such as the cloning of the sheep Dolly). He is also known for his work on embryonic stem cell derivation (together with Frances Brook), demonstrating that ESCs originate from the epiblast and that the most efficient method to derive them in mouse is to use delayed-implanting blastocysts (diapause blastocyst).

The four surviving ICRF Developmental Biology Unit group leaders – Philip Ingham, David Ish Horowicz, Richard Gardner and Jonathan Slack at the BSDB Spring Meeting 2018.

Awards and Honours

  • Waddington Medal of the British Society of Developmental Biology (2018)
  • Patrick Steptoe Memorial Lecturer and medallist (2015)
  • Honorary Doctorate of Science from the University of Cambridge (2012)
  • Annual Lecturer Cumberland Lodge (2010)
  • Honorary Fellow, St. Catharine’s College, University of Cambridge, UK (2007)
  • Knight Batchelor in the Queens’ Birthday Honours (2005)
  • Albert Brachet Prize of the Belgian Royal Academy (2004)
  • Karl Beyer Visiting Professor, University of Wisconsin, Madison, WI, USA (2001)
  • Royal (Queen’s) Medal of the Royal Society (2001)
  • March of Dimes International Prize in Developmental Biology (1999)
  • Elected Fellow of the Royal Society of London (1979)
  • Scientific Medal of the Zoological Society of London (1977)
  • Belfield-Clarke Prize for the Biological Sciences (1966)
  • Elected Scholar of St. Catharine’s College (1966)
  • Kitchener Scholar (1963-66)
  • Prizes for Physics and Biology (1963)
  • First Prize in Natural History Essay (1959)
  • First Prize in Natural History Essay (1958)

Throughout his education and scientific career, Richard has excelled in outstanding performance, as is clearly demonstrated by the long list of awards and honours (see Box); and he has always been a committed member of the Developmental Biology community who contributed notably also in policy making relating to ethical issues connected with access and use of human embryos in research, ethical aspects of cloning, and ethical use of animals in research. His dedication is clearly reflected in the many important positions he served in throughout his career:

  • Editor of the journal Development (formerly J. Embryol. Exp. Morph, 1977-91) and editorial board member of the journals Gamete Research, Placenta and Cancer Surveys
  • President of the Institute of Animal Technology (1986-2006)
  • Independent Member of the Advisory Board for the Research Council (1989-93)
  • together with Walter Bodmer (head of ICRF) he co-founded the Cancer Research UK Developmental Biology Unit at Oxford’s Zoology Department (attracting the likes of Andy Copp, David Ish Horowitz, Jonathan Slack, Julian Lewis and Phil Ingham), of which he was Honorary Director (1986-96)
  • Vice President of the Zoological Society of London (1991-92)
  • Vice-President and Member of the Laboratory Animal Science Association Council (1996-99)
  • Trustee and then chair of the Edward Penley Abraham Research Fund (1999, 2003)
  • President of the Institute of Biology (now Royal Society of Biology; 2007- 08)
  • Chair of the Royal Society Working Group on Stem Cells and Therapeutic Cloning (1998-08)
  • Chair of the Animals in Science Education Trust (AS-ET; current)
  • Author of numerous reports to commissions, committees and inquiries of significant political impact
  • Organiser of various scientific conferences, meetings or discussion forums.

Richard’s enormous influence is also reflected in the fact that he was mentor to many illustrious embryologists, including Janet Rossant (PhD, 1976), Andrew Copp (DPhil, 1978), John Heath (DPhil, 1979), Paul Tesar (DPhil, 2007), Virginia E. Papaioannou (postdoc, 1973-81), Jenny Nichols (PhD, 1990), Karen Downs (1989-93) and the recipient of the 1999 Waddington medal Rosa Beddington (D. Phil., 1983) – to name but a few.

But it should also be pointed out that aside all this prolific work in science as well as science administration and policy, Richard still has been finding time for an impressive number of hobbies, of which he lists ornithology, music, sailing (unfortunately no longer!), gardening, clay shooting and painting landscapes in watercolour. To illustrate Richard’s continued dedication, he donated his latest three watercolour paintings to the AS-ET and they were sold for a gratifying £1150 to provide bursaries and other awards to enable laboratory animal technicians to advance their education and training.

The BSDB would like to congratulate Richard Gardner for the Waddington award, of which he certainly is a most worthy recipient.

An eclectic selection of some of Richard Gardner’s major landmarks publications:

    1. Gardner, RL (1968) Mouse chimeras obtained by the injection of cells into the blastocyst. Nature 220: 596-7 — This paper describes the method of blastocyst injection in which small groups of donor cells derived from a genetically-distinct blastocyst are injected into the blastocoel cavity of a host blastocyst; chimeric blastocysts are then transferred to a foster mother and gestated to term. The paper also demonstrates that blastocyst cells contribute to the adult animal and germ line. The technique of blastocyst injection is still used routinely both to generate transgenic mouse models using genetically-modified embryonic stem cells.
    2. Gardner RL, Lyon MF (1971) X chromosome inactivation studied by injection of a single cell into the mouse blastocyst. Nature 231: 385-6 — Using blastocyst injection of single inner cell mass (ICM) cells combined with genetic markers, this paper shows that the adult animal is derived from the ICM. It is also a landmark paper in the history of the discovery of X-inactivation.
    3. Gardner RL, Papaioannou VE, Barton SC. (1973) Origin of the ectoplacental cone and secondary giant cells in mouse blastocysts reconstituted from isolated trophoblast and inner cell mass. J Embryol Exp Morphol. 30: 561-72In contrast to “blastocyst injection” (above) to determine the fate/potency of ICM cells via injection into the blastocoel cavity, the technique of “blastocyst reconstitution” was created to discover the fate and potency of the trophectoderm. The paper demonstrates that the trophectoderm gives rise to major components of the chorionic component of the placenta but not to the embryo proper. This allowed him to create the first fate maps of the mouse conceptus.
    4. Gardner, RL (1982) Investigation of cell lineage and differentiation in the extraembryonic endoderm of the mouse embryo. J Embryol Exp Morphol. 68: 175-98At implantation, the ICM segregates into epiblast and primitive endoderm (PE). Using blastocyst injection, this paper shows that PE generates visceral and parietal endoderm, which are supporting tissues for the ICM-derived epiblast. This study expanded the mouse fate map to show that ICM gives rise to epiblast and primitive endoderm.
    5. Gardner RL, Meredith MR, Altman DG. (1992) Is the anterior-posterior axis of the fetus specified before implantation in the mouse? J Exp Zool. 264: 437-43 — This paper provides the first evidence that head-tail orientation of the early embryo is established prior to the overt appearance of the primitive streak.
Acknowledgements: Andreas Prokop would like to thank Berenika Plusa for helpful information, Richard Gardner for sending information, images and approving the draft of this article, and Claudio Stern and Jonathan Slack for helpful information and thoughts taken from their nomination text.
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A BSDB history rap!!!!

Posted by , on 13 April 2018

 

This year, is the BSDB’s 70th anniversary! Expect many extras on our Spring Meeting (15-18 April 2018 in Warwick)! For example, the history rap, a contemporary oral rendering of BSDB history, featuring Jerry aka Gerald H Thomsen PhD and produced and mixed by Philip Larsen – BSDB member and DJ!

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