Tag Archives: developmental biology

Richard Gardner is the 2018 BSDB Waddington Medal winner

The Waddington Medal is the only national award in Developmental Biology. 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 position 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 preimplantation 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: 596-7This 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: 385-6Using 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: 437-43This 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.

The Waddington lecture

Emilia Favuzzi: winner of the 2018 Beddington medal

The Beddington Medal is the BSDB’s major commendation to promising young biologists, awarded for the best PhD thesis in Developmental Biology defended in the year previous to the award. Rosa Beddington was one of the greatest talents and inspirational leaders in the field of developmental biology. Rosa made an enormous contribution to the field in general and to the BSDB in particular, so it seemed entirely appropriate that the Society should establish a lasting memorial to her. The design of the medal, mice on a stylised DNA helix, is from artwork by Rosa herself. We would like to congratulate the 2018 winner of the Beddington Medal, Emilia Favuzzi, and would like to take this opportunity to give a brief overview of her career and her PhD project that was awarded the Beddington medal.

Emilia started her studies in 2007 at the Sapienza University of Rome and was awarded a B.Sc. in Biological Sciences with highest marks in 2010. She stayed at the same university for her Master’s project which she performed in the laboratory of Sergio Nasi at the Institute of Molecular Biology and Pathology (CNR, Rome). She completed her M.Sc. in Neurobiology in 2011, again with highest marks. In 2011 she joined the group of Beatriz Rico at the Institute of Neuroscience in Alicante (Spain) and moved with that group to the Centre for Developmental Neurobiology at King’s College London in 2014 where she terminated her project work. Her PhD in Neuroscience was awarded in 2017 by the University Miguel Hernandez of Elche (Spain) also with summa cum laude. Since 2017 she is a postdoctoral associate in Gordon Fishell’s laboratory at the Broad Institute and Harvard Medical School.

 

Fig.1 Activity-dependent gating of parvalbumin interneuron function by the perineuronal net protein Brevican

During her PhD, Emilia worked on two projects which were both based on candidate and genome-wide screen approaches aiming to identify genes that were involved in GABAergic synapse formation. In one project, she investigated the role of perineuronal nets during the synaptic development of GABAergic interneurons. She discovered that the perineuronal net component Brevican is involved in the gating of parvalbumin interneurons by controlling their intrinsic properties as well as extrinsic input through excitatory synapses (Fig.1). This paper was published as a featured article in Neuron (2017). Emilia also took ownership within a parallel project, where she collaborated with another lab member to set up protocols to isolate different populations of interneurons and screen for genes involved in the specific synaptic targeting of cortical interneurons to the different compartments of pyramidal cells. This work led to the discovery of validated candidate genes involved in specific interneuron synapse formation, as shown via loss and gain of function approaches (Fig.2). The respective manuscript is in preparation and Emilia will be shared first author.

Her PhD supervisor Beatriz Rico said about her: “Emilia is a gift for a supervisor: she goes ahead of you, technically and conceptually and pushes you forward. She is brilliant, extremely motivated and creative person and resistant to any difficulties she has found during the development of her project. She never gave up and pursues her aims with an impressive efficiency. She is extremely independent and hard worker. She is fully committed to science, a dream for a supervisor.

 

Fig. 2 Highly selective cell-type specific programs regulate inhibitory synapse specification

Emilia receives the Beddington medal from Simon Bullock

Thesis abstract: Cell-type specific programs regulate the assembly and dynamics of cortical circuits

Understanding how neuronal connections are established and organized in functional networks during development is critical to understand brain function. In the mammalian cortex, GABAergic interneurons are characterized by a remarkable diversity of types and connectivity patterns. As such, they are uniquely suited to orchestrate functionally relevant circuit-specific roles and critically shape cortical function. Yet, how inhibitory circuit specificity is achieved during development is largely unknown. We revealed the transcriptional dynamics of different cortical interneurons during brain wiring and identified subtype-enriched synaptic molecules. Moreover, we showed that the functional connectivity of different interneurons relies on the cell-specific expression of such synaptic genes. Altogether, our results demonstrate that highly selective molecular programs emerging during development in cortical interneurons support their early wiring and underlie inhibitory circuit specificity. After their integration into canonical circuits, activity-dependent plasticity endows neurons with the flexibility required for adapting to sensory experience. Parvalbumin (PV+) interneurons have been shown to play a critical role in this process but the molecular mechanisms by which experience influences PV+ interneuron plasticity were poorly understood. We revealed how perineuronal net (PNN) proteins drive PV+ cell wiring as well as network adaptation to experience. We showed that the PNN protein Brevican simultaneously regulates the excitatory inputs and firing properties of PV+ interneurons by controlling the localization of AMPA receptors and potassium channels, respectively. We also showed that, by modulating Brevican levels, experience influences cellular and synaptic forms of plasticity in PV+ cells and this is required for normal cognitive function. These findings uncover a cell-specific molecular program through which a PNN protein dynamically gates PV+ interneuron function both during development and upon experience-dependent plasticity.

 

Papers by Emilia so far (* co-first authors)

Favuzzi E*, Deogracias R*, Marques-Smith A, Maeso P, Exposito-Alonso D, Balia M, Jezequel J, Kroon T, Hinojosa AJ, Rico B. Highly selective cell-type specific programs regulate structural synapse target specificity (manuscript in preparation) 

Favuzzi E, Marques-Smith A, Deogracias R, Winterflood CM, Sánchez-Aguilera A, Mantoan L, Maeso P, Fernandes C, Ewers H, Rico B. Activity-dependent gating of parvalbumin interneuron function by perineuronal net proteins. Neuron (2017)

Marques-Smith A*, Favuzzi E* & Rico B. Shaping Early Networks To Rule Mature Circuits: Little MiRs Go A Long Way. Neuron (preview), (2016)

Annibali D*, Whitfield JR*, Favuzzi E, Jauset T, Serrano E, Cuartas I, Redondo-Campos S, et al. Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis. Nature Communications (2014)

Savino M, Annibali D, Carucci N, Favuzzi E, Cole MD, Evan GI, Soucek L, Nasi S. The Action Mechanism of the Myc Inhibitor Termed Omomyc May Give Clues on How to Target Myc for Cancer Therapy. PLoS One (2011)

The new BSDB Newsletter: a focus on communication & advocacy

Please, have a look at the newest issue of the BSDB newsletter, which can be downloaded here. It covers two eventful years of our society’s history and is by far the longest ever published! This seems only appropriate considering that 2018 marks the 70th anniversary of the BSDB’s foundation. In recognition of its history, the BSDB has decided to digitise all its newsletters which have recently been re-discovered in an almost forgotten archive. They will be gradually uploaded on our archive page (bsdb.org/about-us/bsdb-newsletters) where issue no. 1 from 1979 has already been linked out to get the ball rolling. We have now first lists of the archive’s contents which seem to date back to the early 60s. If you have an interest in these, please contact comms@bsdb.org. Also, if you have further thoughts on how to catalogue and store the archive safely for the future, please let us know.

Editorial: My final newsletter – and some thoughts about communication

This is my final newsletter as communications officer of the BSDB. I must admit that I enormously enjoyed the task, and can only hope that the changes to our website and the ways in which the society has been represented during my time in office are seen positively by our members. It is my pleasure to announce that Ben Steventon (p.6) has agreed to take over as BSDB communication officer from autumn 2018. I am confident that he will do a brilliant job.

Unlike previous editions, this newsletter covers two years of our society’s life. But honestly, did you even notice the delay? Extrapolating from the download metrics of former newsletters, the long gap is very likely to have gone widely unnoticed, and I can see two reasons for this. Firstly, on the positive side, all our society news is now being published more promptly on our website or on The Node. This changes the nature of the newsletter from being a source of primary information, and turns it into a legacy item or even a historical document for future BSDB generations. This is reason enough for the BSDB to continue with its newsletter. Secondly, a reason of more concern is that the low viewer numbers likely reflect a tendency of communication fatigue in our community. Let me briefly extend on these thoughts before outlining the content of this newsletter.

The BSDB informs promptly online

If I have done my job well for the last two years, the contents of this newsletter should no longer be news to you, but rather be a reminder of our active society life during this period. I have made every effort that news was brought to you promptly via our website or through The Node. Of these, The Node has become an increasingly important medium.

Maintained by The Company of Biologists as a communication platform for the community of biomedical scientists, it has taken on the form of a modern electronic newsletter that reaches out internationally. As explained in a recent publication, The Node’s community manager Aidan Maartens either authors or commissions meeting reports, book reviews, obituaries or interview transcripts, and collates community-relevant information about meetings and workshops. Importantly, we as individuals or societies can use The Node as a communication platform to advertise jobs and events, write about science-related topics, explain our latest publications, or share community-relevant experiences. Once registered, we can publish freely and ‘uncensored’ as long as we keep within The Node’s reasonable rules. In this way, we can capitalise on a very well established communication platform, which is further enhanced by The Node’s Twitter and Facebook accounts, each with thousands of followers. Much of the science-related news that would previously have been disseminated via the BSDB newsletter or website, is being covered by The Node, taking an enormous work load off my shoulders – and the same can likely be said for Developmental/Cell Biology societies worldwide. There is true synergy and, naturally, more community members visit The Node’s website than the BSDB’s. Consequently, I closely collaborate with Aidan and follow a strategy in which many of our news posts are published on The Node – of course always making sure that they are likewise accessible through our own site.

This said, the BSDB website still has an important purpose. User metrics indicate that our site has its prime function in BSDB-specific information, such as our conference and travel grants, awards and meetings and committee information. I take great care that these pages are updated as soon as new information is available. Please, let me or Ben know if there is anything that’s wrong or missing – we’ll act swiftly.

Is our communication failing?

Regardless of whether newsletters occur in static journal format or as dynamic websites, they often are important motors for scientific communities and their science, as is well explained in an article by C. M. Kelty from 2012. But does this strategy still work effectively? I sometimes feel that we were better informed in pre-internet times when information was less abundant but focussed on the essentials, and when dissemination was easier because the readership was hungry for information. Today, we tend to see quantity over quality: more than a hundred emails rain into our accounts every day, and social media timelines have become so busy that there is hardly time to view even a fraction of the messages. And, even if information is being read, I see little evidence that this leads to impactful social media debates. Furthermore, the sharing of information on social media is short-lived and often ineffective as can be deduced from viewer metrics of shared links. Even the use of social media as a mere source of professional information seems to fail: a survey by The Node showed that most members of our community have no Twitter account. Even more alarmingly, subscription rates to websites are low (~900 for The Node and ~150 for the BSDB), when considering that the BSDB alone has a ~1400 strong membership. In a nutshell, besides not reading the newsletter, many of us are not tapping into the existing online community news channels.

In consequence, important information can no longer be disseminated effectively and reliably, and our community no longer has the means to develop a common voice. This clearly weakens us in times where the need for communicating the importance of fundamental science is perhaps greater than ever. In recognition of this challenge, many contributions in this issue are dedicated to the topic of science communication: our chair Ottoline Leyser speaks about the importance of communication (p.4); a dedicated article explains the BSDB’s advocacy campaign in collaboration with The Node (p.23); an overview of a recent special issue on science communication in the field of biomedical science is being provided (p.27); our student and postdoc representatives announce a writing competition aiming at advocacy (p.31); the example of an advocacy article for Open Access Government is given (p.78).

Further contents of this issue

As usual, the start of this newsletter is made by the chair’s and officers’ reports. In the chair’s address (p.4), Ottoline Leyser reflects on the BSDB as an inclusive, co-operative, and outward looking society, and the need to uphold these traits in times of Brexit and worldwide political tendencies of isolationism; Ottoline ends her address with some thoughts on the importance of communication. The secretary’s report by Kim Dale (p.5) highlights the positive developments of the BSDB in terms of its steadily growing membership. She notes that, in 2018, the committee will see a turn-over of 5 members (see also p.7) – so await a call for nominations before the next Spring Meeting. In the same vein, the three new members that have joined the committee in 2017 are being introduced on page 6. The meetings officer Joshua Brickman (p.9) looks back at the BSDB’s excellent meeting record of the last two years (see also meeting reports on pages 11 and 14), and gives an outlook on the exciting meetings planned for the next three years (see also p.10), including the BSDB’s 70th anniversary meeting taking place 15-18 April 2018 in Warwick (see this issue’s cover image). The treasurer’s report by Chris Thompson (p.19) is an impressive account of the high number of members that were supported to attend meetings or workshops in 2016 and 2017, and sends out the reconfirming message that our financial status remains solid, providing the BSDB with continued capacity to support its members and their science-related activities. Our student & postdoc representatives, Alexandra Ashcroft and Michelle Ware (p.30), report about their outstanding efforts to deliver on the requests of junior members expressed during the survey from 2015. In response, Alex and Michelle introduced a very successful career workshop (see the respective reports on p.32) and a new career website (detailed on p.35). Finally, the newsletter concludes with reports about our main awardees of the last two years, in particular the winners of the Waddington (p.38), Cheryll Tickle (p.41) and Beddington medals (p.45), as well as the two Dennis Summerbell awardees (p.47), and 14 project reports by students who were supported by the Gurdon/The Company of Biologists Summer Studentship scheme. See a complete overview of all awardees, including poster prize winners (p.36) – and remember that most award lectures were documented and are available on our YouTube channel.

Andreas Prokop