Here are the research highlights from the current issue of Development:

Nodal regulates germ cell potency

During mammalian gonadal development, somatic cues regulate the sex-specific development of foetal germ cells and control the transition between proliferation and cell-fate commitment. This transition is particularly important for male germ cells: too little proliferation reduces sperm numbers and fertility, whereas escape from commitment and prolonged pluripotency can cause testicular germ cell tumours. Now, Josephine Bowles, Peter Koopman and colleagues (p. 4123) report that the TGFβ morphogen Nodal regulates this transition in mice. The researchers show that Nodal signalling is active in XY germ cells at the developmental stage when this transition occurs and that Nodal signalling is triggered when somatic signals, including FGF9, induce testicular germ cells to upregulate the Nodal co-receptor Cripto. Genetic suppression of Nodal signalling leads to depressed pluripotency marker expression and early XY germ cell differentiation, they report, whereas NODAL and CRIPTO are upregulated in human testicular tumours. These results indicate that Nodal signalling regulates male germ cell potency during normal development and provides new clues about the aetiology of testicular cancer.

Cardiomyocyte migration mends broken hearts

Unlike adult mammals, adult zebrafish can regenerate injured heart tissue. Heart regeneration in zebrafish is known to involve partial de-differentiation and proliferation of cardiomyocytes, but are cardiomyocytes involved in any other processes during heart repair? Here (p. 4133), Yasuhiko Kawakami and co-workers report that cardiomyocyte migration to the injury site is required for zebrafish heart regeneration. Ventricular amputation, they report, induces expression of the chemokine ligand cxcl12a and the chemokine receptor cxcr4b in epicardial tissue and cardiomyocytes, respectively. Both pharmacological inhibition of Cxcr4 function and genetic loss of cxcr4b function prevent heart regeneration, they show, and lead to mislocalisation of proliferating cardiomyocytes outside the injury site without affecting cardiomyocyte proliferation. Finally, the researchers use a photoconvertible fluorescent marker to show that, although cardiomyocytes migrate into the injury site in control hearts, their migration is inhibited in Cxcr4-antagonist-treated hearts. Thus, cardiomyocyte migration into injured zebrafish heart tissue is regulated independently of cardiomyocyte proliferation, and coordination of both processes is essential for heart regeneration.

Hox genes specify nephric ducts

In amniote embryos, three kidneys – the pronephros (a transient embryonic structure), the mesonephros (the embryonic kidney) and the metanephros (the adult kidney) – form sequentially along the anterior-posterior (AP) axis of the intermediate mesoderm (IM). Here (p. 4143), Thomas Schultheiss and colleagues investigate AP patterning in the mesoderm by analysing the specification of the avian embryonic nephric duct – an unbranched epithelial tube that originates in the anterior IM. Using quail-chick chimaeric embryos, the researchers show that nephric duct specification occurs early in development when IM precursor cells are still in the primitive streak. HoxB4, they report, is expressed in nephric duct precursors from the primitive streak stage onwards, whereas the more posterior Hox gene HoxA6 is expressed in non-duct IM. Notably, misexpression of HoxA6 in the duct-forming regions of the IM represses duct formation. Together, these results indicate that Hox genes regulate AP patterning in the IM and provide new insights into general mesodermal patterning along the AP axis and into kidney evolution.

Cohesin quells Polycomb group silencing

Polycomb group (PcG) genes encode transcriptional repressors that regulate gene expression during development. Most PcG genes encode subunits of chromatin-modifying complexes, but exactly how PcG proteins repress transcription is unclear. Now, Judith Kassis and colleagues report that Wapl, a cohesin-associated protein involved in cohesin removal from chromosomes, promotes PcG silencing in Drosophila (p. 4172). To identify genes involved in PcG silencing, the researchers conduct a screen for suppressors of silencing mediated by an engrailed PcG response element. They identify one of the suppressors obtained from this screen as wapl^AG, a dominant wapl mutation that produces a truncated Wapl protein. The researchers show that wapl^AG hemizygotes die as pharate adults (insects prior to emergence from pupae) but have an extra-sex-comb phenotype similar to that produced by mutations in PcG genes. Finally, the researchers show that Wapl-AG increases the stability of cohesin binding to polytene chromosomes. Together, these results suggest that increasing cohesin stability can interfere with PcG silencing, and that cohesin thus directly inhibits PcG function.

Human skin innate immunity develops early

The skin protects the body from microbial pathogens by employing Toll-like receptors (TLRs) and other molecules that recognise pathogen-associated molecular patterns to initiate innate immune responses and to direct subsequent adaptive immunity. But when does the innate immune system in human skin become immunologically competent? On p. 4210, Adelheid Elbe-Bürger and co-workers answer this question by analysing TLR expression and function in human skin. The researchers report that, although prenatal and adult skin express a similar spectrum of TLRs, prenatal, infant and child skin express higher levels of several TLRs (particularly TLR3) than adult skin. Moreover, a synthetic TLR3 ligand that mimics viral double-stranded RNA significantly enhances the secretion of several chemokines and cytokines by keratinocytes isolated from foetal and neonatal donors but not by those isolated from adult donors. Thus, the researchers conclude, human skin exhibits age-related changes in TLR expression and function, and foetal keratinocytes are already endowed with specific immune functions that may protect the developing human body from viral infections.

Calcium crosstalk during plant fertilisation

During sexual reproduction in flowering plants, cellular interactions guide the growth of the pollen tube from the stigma to the embryo sac where fertilisation occurs. The cytoplasmic Ca²⁺ concentration ([Ca²⁺]_cyt) regulates pollen tube growth, but does it also regulate pollen tube guidance and reception? On p. 4202, Seiji Takayama and colleagues investigate Ca²⁺ dynamics during fertilisation by expressing a Ca²⁺ sensor in Arabidopsis pollen tubes and synergid cells (cells in the ovule that guide the pollen tube). During semi-in vivo fertilisation, they report, pollen tubes turn towards wild-type ovules but not towards ovules in which pollen tube guidance has been genetically disrupted. Notably, [Ca²⁺]_cyt is higher in turning pollen tube tips than in non-turning tips. Moreover, [Ca²⁺]_cyt oscillation in the synergid cells, which reaches a maximum at pollen tube rupture, begins only upon pollen tube arrival. These results suggest that signals from the synergid cells induce Ca²⁺ oscillations in the pollen tube and vice versa, and that these oscillations are involved in pollen tube guidance and reception.

Plus…

The year 2012 marks 25 years since the journal Development was relaunched from its predecessor, the Journal of Embryology and Experimental Morphology (JEEM).  To mark a quarter century of Development, we have been looking through our archives at some of the most influential papers published in Development’s pages. In a series of ‘Development Classic’ articles, we have asked the authors of those articles to tell us the back-story behind their work and how the paper has influenced the development of their field. The first two of these articles (see below) are published in this issue – look out for more of these Spotlight papers in the next few issues.

The ABC model of flower development: then and now

In 1991, John Bowman, David Smyth and Elliot Meyerowitz published a paper in Development that proposed the ABC model of flower development. Now, the authors look back on their paper and discuss several aspects of this story.

See the Spotlight article on p. 4095

The zebrafish issue of Development

In December 1996, in a special issue of Development, 37 papers reported the results of two large screens for zebrafish mutants performed in Tübingen and Boston. Now, Christiane Nüsslein-Volhard gives a personal account of the history of this unique endeavor.

See the Spotlight article on p. 4099

Eph/ephrin signalling during development

Eph receptors and their membrane-tethered ephrin ligands have important functions in development. Rudiger Klein provides an overview of the general structures and signalling mechanisms underlying Eph/ephrin signalling in development.

See the Development at a Glance poster article on p. 4105

In vitro organogenesis in three dimensions: self-organising stem cells

Organ formation during embryogenesis is a complex process that involves various local cell-cell interactions at the molecular and mechanical levels. Yoshiki Sasai and colleagues discuss how, despite this complexity, organogenesis can be modelled in vitro using stem cells.

See the Review on p. 4111

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Postdoctoral Researcher
Morphogenesis during animal development

The Sars International Centre for Marine Molecular Biology is now offering a two-year postdoc position in a research group working on morphogenesis using the notochord development in Ciona intestinalis as the model. The announced position focuses on the construction and regulation of the actomyosin network that is involved in cell elongation during the early phase of notochord tubulogenesis. Interested individuals can read two publications, Dong et al., 2011, and Denker and Jiang, 2012, for detailed description of experimental model and the biological questions.

Extensive resources are established for Ciona intestinalis (gene knock down, transgenesis, advanced imaging tools, quantitative analysis of morphogenesis, and published genome).

The position will utilize a broad spectrum of cell biology methods. Applicants with special interests in cytokinesis, actomyosin, advance quantitative imaging are welcome to apply. Prior experience in microinjection and/or dynamic live imaging of embryos are preferred. We seek creative scientist who wishes to explore new experimental system and discover novel mechanism.

The position is available immediately; the start date is negotiable. The salary for Postdoctoral Researcher (code 8151) starts at NOK 480 000.

The Sars International Centre is a partner of the European Molecular Biology Laboratory (EMBL) and a department of Uni Research AS, affiliated with the University of Bergen. The Centre is focused on basic research in marine molecular biology, developmental biology and evolution, through genetic and comparative studies of invertebrates and vertebrates.

Uni Research has employee insurance and pension agreements and is an equal opportunity employer.

For further information regarding the position and scientific content of the project please contact Dr. Di Jiang, Group Leader: di.jiang@sars.uib.no.

Written applications in English, including CV, summary of educational and work experience, a brief statement of research interest and contact information for two references can be sent to: Uni Sars Centre, HR Officer, Bergen High Technology Centre, Thormøhlensgt. 55, N-5008 Bergen, Norway. Please mark applications 12 Sars 08. Application deadline is November 9 2012.

Please note that applications sent by e-mail will not be considered.

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At the EMBO meeting last month, Jiří Friml was awarded the EMBO Gold Medal. This medal is awarded annually to a researcher under the age of forty, who has contributed to the field of molecular biology. Friml got the award for his work on auxin transport and morphogen gradient formation in plants. In his Gold Medal Lecture, he gave an overview of auxin signaling and PIN proteins, and discussed recent discoveries that describe how plants grow in response to light and gravity. The next day he braved a sudden burst of heavy rain to meet me for an interview for the Node:
 
Why did you decide to study plant developmental biology?
 
It was not a decision; it was a coincidence. I got a DAAD fellowship to study in Germany for ten months, and went to the lab, which my department in the Czech Republic had contact with. This lab was rather focused on molecular biology and plant physiology. When I started to do my project I realized that there are a lot of developmental biology consequences, and I liked it a lot and then pursued this area further on my own.
 
You’ve worked in several different countries over your career. Have you seen any particular differences, for example between Germany, Belgium, the Czech Republic? Or is it all quite similar within Europe?
 
I have to say I was surprised how big the difference is between Germany and Belgium. I mean the difference in mentality and culture of the people, which, to some extent, reflect on science. Germans are famous for being a bit more strict, but on the other hand, they are also extremely reliable, which is very convenient for professional things. Once you’re working in the lab, I don’t see that big a difference between cultures, though. My teams have always been very international: In Belgium I had two Belgians in a lab of twenty so the geographical location didn’t influence the work in the group so much. Many differences between labs are also dependent on what type of institute you are at, and even within one country there is wide variety between institutes or between universities.
 
I also noticed, that the education system varies between countries. PhD students from the UK are younger and less experienced simply because the education system is different from that in Germany for example.
 
And in the Czech Republic, after twenty years of being open to the world, there is still a legacy of the fact that genetics was suppressed as a “capitalistic doctrine” during the communist regime. Therefore the country has basically missed a whole generation of geneticists. This is still not fully replaced, so even though other fields like hormonal physiology are very good, anything that requires genetics, and that means most of developmental biology, is underrepresented.
 
Do you think that’s going to change any time soon?
 
Well, that’s what we have believed for twenty years now. And it is changing. It’s definitely changing. But, universities are stubborn structures, not only in the Czech Republic, so it’s very difficult to create new departments because that would be usually on the expenses of the old ones.
 
When you accepted your medal, you said “I’d like to take this as an appreciation for the plant field” and in your talk you showed a slide emphasizing all the things of which people may have forgotten that they were originally discovered in plants: cells, genes, siRNA. Why is plant science under-appreciated?
 
I wouldn’t say it is under-appreciated. Drosophila science is probably also under-appreciated in comparison to biomedical research. I think there are logical reasons that biomedical research gets more attention. In Europe we are seldom hungry, but we still get cancer and Alzheimer and AIDS. The issues of our health are more important to everybody – including plant scientists –than the issues around improving the quality of food. As a result, plant science is less represented than biomedical research, but I didn’t want to make it seem like we feel under-appreciated, I just wanted to show my own appreciation for my colleagues in the plant field.
 
In your talk you showed, to roughly summarize it, why plants grow upward. What are the next questions to be answered?
 
Even though we may understand the basic concepts from the developmental biology point of view, we are still far from really knowing every single step of the molecular signaling pathways underlying the developmental decisions. For example, we’re just starting to understand how the crosstalk between the signaling pathways works: That’s something that is now being worked on in the field of plant signaling.
 
My personal big question concerns the evolutionary aspect of plant development. With next generation sequencing technology, many of the more primitive plant species are now being sequenced and becoming accessible to study. I’m interested in finding out how plants colonized land, because before plants grew on land roots didn’t need to grow down, and shoots didn’t need to grow up. Many of these auxin-mediated responses are typical for land plants. What we are now interested in is how acquiring these cellular mechanisms helped the plant to adapt to life on land. From the evolutionary point of view, what we also often encounter is an evolutionary conserved cellular mechanism, like clathrin-mediated endocytosis for example, with a plant-specific regulator that somehow feeds into the pathway. We’re trying to understand how that happened, how these new plant-specific regulations were recruited by the conserved mechanisms during evolution.
 
If you had unlimited time and money, what would you love to investigate?
 
I would invest in the establishment of new model species at the lower plant level and at algae level to really try to understand how the plant developmental machinery evolved. I would sequence all these species and get people to establish transformation methodology and develop genetic model systems. But this type of thing will be happening anyway: different labs will each do a piece and at the end of the day we will get there.
 
Do you have any advice for students and postdocs who are just starting their research career?
 
They should take responsibility. What I see with many students is that they rely too much on what they are told. They are clever, they are working hard, but they are not taking the project as their own and taking their career and life in their own hands. I cannot generalize, because people are different, but I see that this is a major obstacle for many talented young scientists in achieving what they want. They either don’t have enough self-confidence, or they don’t fight enough for it.

(8 votes)

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The Genetics Society’s 2012 Autumn Meeting celebrating the 25th Anniversary of Genes & Development

There have been exciting advances in molecular analyses of genetic and epigenetic regulation of key cellular processes.  This meeting will  focus on issues such as chromatin, epigenetics and gene regulation, replication, checkpoints and DNA repair, RNA function and control as they apply to processes of development, stem cells and diseases such as cancer.

This meeting is sponsored by the Genetics Society and celebrates the 25th anniversary of the journal Genes and Development of which the Genetics Society has been a founding participant. The speakers are all distinguished leaders in their respective fields and will present and discuss recent and exciting research developments.

Features

Steve West the 2012 Genetics Society Medal recipient

Speakers

Bruce Stillman
Sharon Dent
Steve Smale
Jerry Workman
Ken Zaret
Titia de Lange
Steve Elledge
Steve Jackson
Susan Gottesman
Elisa Izaurralde
Narry Kim
Jim Manley
Joan Steitz
Hans Clevers
Elaine Fuchs
Nick Hastie
Rich Losick
Eileen White

Chairs

Terri Grodzicker
Rudi Grosschedl
Winship Herr
Davor Solter

Scientific Organisers

Anne Ferguson-Smith
Terri Grodzicker
Nick Hastie

Registration deadline: 26 October 2012

Registration is now available for the whole Autumn Meeting and to attend just one day of the meeting.

(1 votes)

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Just a reminder that registration for Development‘s 25th anniversary symposium “Past, Present and Future” is closing at the end of this week. By Monday, the venue will need to know who is attending, so make sure to sign up this weekend at the latest.

The symposium will be held at Cripps Court (Magdalene College) in Cambridge, on October 25th. We’ve got some great speakers lined up: Kenneth Chien, Magdalena Götz, Peter Lawrence, Thomas Lecuit, Mike Levine, Olivier Pourquié, and Jim Smith.

Don’t forget to register!

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Despite the fact that I write this meeting post after three weeks of the summer school, I feel as though I’m writing directly from the Hydra Island, the experience and memories are that fresh!

I was fortunate enough to be selected to participate in the 8th European Summer School on Stem Cells and Regenerative Medicine held in Hydra, Greece from 15 – 21 September, 2012. Hydra is a unique Saronic Island located in the Aegean Sea. Known for its place in Greek war and it’s special donkey-mode-of-transportation, Hydra is a picturesque Mediterranean sunshine spot. No other places would be as perfect as this location for a summer school. Thanks to the organizers! On a discrete note, there are small group of fresh-water Cnidarian animals known also as Hydra. I am tempted to draw the connection between this and stem cells, as these creatures possess great regenerative ability!

The summer school began with a plenary lecture by Shin-Ichi Nishikawa. He took us through his research and experiments during his early career on the development of haematopoietic stem cells. He also touched the classic embryological aspects of haematopoietic stem cells.

The next six days lectures were divided into three broad themes within stem cell biology: 1. Paradigm stem cell systems 2. Regulation and dysregulation 3. Into the clinic. Leaders in the respective fields presented lectures in these themes. It was rather exciting to sit and listen to those speakers whom I know through their breakthrough publications in the field of stem cell biology. While Cédric Blanpain and others explained how tissue homeostasis is maintained by distinct tissue-resident stem cells, Austin Smith introduced us the world of embryonic stem cells. I personally enjoyed the talk by Elena Cattaneo on neural stem cell biology. Her research on evolutionary aspects of Huntingtin gene and relating that to neural stem cell based therapy for the Huntington disease was particularly exciting.

Mathematical and computational approaches to stem cell biology are the imperative tools to tackle any questions especially with the availability of overwhelming data. Alexander Van Oudernaarden, Timm Shroeder and Markus Loeffler discussed quantitative and computational modelling approaches in their research. Participants also learned about the ethical aspects of stem cell research from two specialists in the field, Göran Hermerén and Aliki Nichogiannopoulou. I realised how important it is to consider ethics in biology especially when we are dealing with a sensitive area. Hermerén’s another interest is philosophy of science; it was nice chance for me to engage in thought-provoking philosophical discussions with him. Michele De Luca, Tim Allsopp and Guilio Cossu presented their exciting and ambitious clinical research aimed at cell therapy for different disorders.

Unlike other schools or workshops, the Hydra summer school, along with regular lectures, featured other unique activities like “Inspire”, “Communicake” and small workshop on how to get your research published. Inspire sessions need special mention here; one session each day focused special topics on how to communicate our research to non-science audiences. Communicating research work to the public is of paramount importance in any science. Being involved myself in this activity in my institution on a voluntary basis, I see many young researchers do not realise how important is this. Inspire sessions in this summer school unquestionably a great exposure to the participants and I am sure this has given motivation to all of us to continue doing this back home. Cathy Southworth and Jan Barfoot of MRC Centre for Regenerative Medicine, University of Edinburgh jointly conducted these Inspire-ing activities. “Communicake” sessions provided participants in small groups with an opportunity to recollect previous sessions and presenting back the key points on the topics to the speakers. Katherine Brown, Development’s Executive Editor, discussed key aspects of how to get our research published and publication ethics.

Another attraction of the school was the movie evening. The film “Stem Cell Revolutions” was screened during one of the evenings. This was fitting entertainment when we have learned about stem cells the whole day, and the movie shows us how the field has revolutionised stem cell science for patient benefit. We thoroughly enjoyed the film. A review of the film by my colleague Claire Cox can be found here.

Along with poster sessions (congrats to the prize winners!), dedicated small group discussions provided participants with a fantastic opportunity to discuss more informally about their chosen topics with leaders in the field. The summer school was organized in such a way to cover broad areas within stem cell biology with other supplemental sessions. Wide-ranging topics matched with participants’ heterogeneous background from computational biology to mouse genetics. A computational biologist’s experience on this summer school can be found here. My expectations were certainly very well met in this school, and I hope that’s true for all the participants.

There is a huge prospect for the field of stem cell biology in the future, from understanding to alleviating diseases. Lectures and discussions at the summer school gave me confidence that this is a realistic goal. As an extra boost and recognition to the field, it’s been great this year to see the Nobel Prize awarded to the doyens for their work in stem cell biology. As I write this report, I can hear the celebrations from our neighbours at Sir John Gurdon’s centre! Certainly, it is a great excitement for young researchers like me to be in this promising field and to embrace the opportunity to meet and get to know leaders in the field and my peers alike through events like Hydra. I am thankful to OptiStem for their support for making it possible for me to attend the summer school and make most out of it. Anyone fancy attending Hydra next summer? Who wouldn’t want to enjoy Sun and Science together?

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(3 votes)

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To me, the stem cells within a germline are a perfect storm of fascination.  Stem cells are, of course, intriguing in their ability to self-renew and differentiate, and a germline is intriguing in its ability to generate gametes.  Add stem cells and germlines together, and you have amazing biology in front of you…and more biology to discover and understand.  Today’s images are from a paper describing mRNA regulation in germline stem cells in C. elegans.

The C. elegans germline is set up as a U-shaped tube of differentiation and gamete production.  At the distal end of the germline, a niche of stem cells constantly divides throughout the life of the worm.  These mitotically dividing cells get pushed along the germline as more cells are produced, and accumulate low levels of meiotic proteins until entering the transition zone in preparation for meiosis.  P-granules are RNA granules, or nuage, found within the C. elegans germline.  P-granules localize to the nuclear envelope and have been suggested to directly regulate mRNAs exported from the nucleus, as a form of post-transcriptional control over gene expression.  A recent paper describes results showing the importance of P-granules in mRNA regulation within germline stem cells.  Voronina and colleagues show that two 89% identical PUF family RNA-binding proteins, FBF-1 and FBF-2, have important and distinct functions in regulating meiotic mRNAs.  FBF-1 regulates the degradation or transport of meiotic mRNAs out of the stem cell region, while FBF-2 prevents translation of meiotic mRNAs.  In addition, Voronina and colleagues found that FBF-2 is dependent on PGL-1, a P-granule component, for proper nuclear localization and binding to target mRNAs.  The use of different mechanisms to prevent meiotic protein expression within the stem cell region ensures that the germline can function properly.

The cartoon above shows the different zones of the germline, with germline stem cells dividing in a niche at the distal end (left side).  The images show the nuclei (blue) of cells in the mitotic zone in the germline.  FBF-1 (green, top) and FBF-2 (green, bottom) are found at distinct foci around the nuclei.  FBF-2 is found primarily on P-granules (PGL-1, red, bottom row).

For a more general description of this image, see my imaging blog within EuroStemCell, the European stem cell portal.

Ekaterina Voronina, Alexandre Paix, & Geraldine Seydoux (2012). The P granule component PGL-1 promotes the localization and silencing activity of the PUF protein FBF-2 in germline stem cells. Development, 139 (20), 3732-3740 DOI: 10.1242/dev.083980

(1 votes)

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As you’ve almost certainly heard, this year’s Nobel Prize in Physiology or Medicine has been awarded to Professor Sir John Gurdon and Professor Shinya Yamanaka. This is thoroughly deserved recognition for groundbreaking work that not only provided revolutionary insights into the nature and plasticity of the genetic material inside each cell, but has also opened up promising avenues for personalised stem cell therapies.

Here at the Company of Biologists, we’re particularly delighted that John has been honoured with this prize. He has been involved with CoB for many years, and was the Chair of our Board of Directors from 2000 to 2011 – this picture of him now hangs in our corridor…

During John’s time as CoB Chairman, the Node was launched – with his full support. Indeed, we even hosted our launch party at the institute that bears his name, as evidenced by the photo! For a man who, according to his science teacher, would never make a scientist, I think it’s safe to say that he’s not done badly… From personal experience, I can also divulge that, not only is he an outstanding scientist – still running a highly productive lab at the age of 79 – but he’s also a mean croquet player!

Many people have written much more eloquently than I could about John and Shinya’s contributions to the reprogramming field, so I’ll just add my voice to the chorus of congratulations!

(12 votes)

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The Hydra Summer School presents a unique opportunity to young scientists in the field of stem cell research to engage with leading experts and peers alike. Set on an idyllic Greek island, where you’re more likely to encounter the wrong side of a donkey than a bicycle or car, an intensive week-long programme of lectures, discussions, debate and discourse unfolds. The programme spans the fundamental paradigms that underlie stem cell systems through to the state-of-the-art in clinical practice, and covers the breadth of stem cell research in-between.

In relating my experience of the summer school, it is necessary to divulge my dirty secret: I’m not a biologist. My undergraduate degree was in Mathematics, and my Phd undertaken within a Computer Science department in a group that comprised physicists, engineers, computer scientists and mathematicians, all carrying out cross-disciplinary research in computational modelling of biological systems. Worldwide, we are an expanding group, and engagement with biologists is key to the success and value of the research we perform. Without formal biological training, it is vital for physical scientists to absorb information from biologists directly – it is quite difficult to have a conversation with a book, bordering dangerous to do so on the internet, and we are simply unarmed when it comes to discerning the quality of new biological research and publications. It is with this motivation that I set off to Hydra.

The breadth of research covered by the lectures was excellent, allowing the attendees to engage both in new topics as well as with their own specialisation. Some of the most interesting lectures illustrated the application of stem cell research in understanding disease onset and progression, as more often than not the focus can be on the fully developed disease itself, rather than understanding what is stable under normal, healthy conditions. By understanding a healthy system fully, only then can we isolate the aberrant changes, and discern how best to implement stem cell therapies.

Personally, I particularly enjoyed the recurring discussion on the definition of a stem cell, and how one must be aware of the language subtleties that exist between different researchers and sub-disciplines. Is a fertilised egg a stem cell? Perhaps, if you’re a developmental biologist. Relevant in this context is the concept of asymmetric division, which we were challenged to think more deeply about. Despite what may seem, there is little empirical evidence to support different models of division through lineage progression. Moreover, for asymmetric division to occur, at which point is the decision made by the cell? Is it intrinsic, and thereby a consequence of mitosis itself, or is it extrinsic, and thereby dependent on the extracellular environment into which one daughter cell is placed?

Supplementing the lecture topics were discussion sessions with the individuals PIs, a rare opportunity to engage with these scientists in a small group setting. The discussions that I participated in were accompanied by recent and not-so-recent-but-important papers, chosen by the discussion leader. I found it particularly useful to engage with biologists over these papers, to understand how a biologist reads a paper, and to learn a little more about how to be discerning in your reading. Another very useful supplement to the lectures was a session entitled, “Communicake!” (Regretful disclaimer: no cake was provided.) This was a session in which participants reviewed specific lectures in small groups, and in tandem with the lecturer themselves, drew up a list of the key points that were conveyed in the talk, and had a further opportunity to ask the lecturer more questions. I confess this gave me the opportunity to ask a couple of my more “stupid questions”, but it was extremely helpful to have focused discussion on specific lectures, and I am now a big advocate of review sessions such as these.

On top of this, as an on-going feature of the week, were the posters brought by all participants on their own research. Again, this provided the opportunity for interesting discussions, the odd stupid question, and for me personally, the chance to really engage with the research being conducted on a day to day basis by my peers. The poster prizes themselves were awarded deservingly (don’t worry, not by me – I made it safely into the “also-ran” category).

I am very grateful that I was given the opportunity to attend the Hydra Summer School, and am happy to give a brief report which gives a glimpse into the usefulness and breadth of the experience. So without hesitation, be you biologist, mathematician, physicist or engineer, I encourage you to apply for this opportunity if you are working in stem cell research. In the very least, you’ll like the donkeys.

(5 votes)

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In the middle of the worst political and financial turmoil Spain is experiencing since the return of its young democracy, the 1st Spanish Conference on the Molecular, Cellular and Developmental Biology of Drosophila emerges as an example of how science in Spain can and should be done. The history of Spanish Drosophila research started in the late 60s and has since then been very intense. In 1968 Antonio García Bellido started the first lab working on Drosophila where he set up a long term research project on the analysis of development in terms of genes and cell behaviour. Ideas and frameworks developed in his lab influenced the field of Developmental Biology across the world. Since then and for the last 45 years, the Spanish Drosophila research community has expanded both geographically and scientifically.

The conference, organized by Jordi Casanova and Tano González in the idyllic site of Aiguablava (Girona), gathered principal investigators from several parts of Spain (Alicante, Barcelona, Bilbao, Madrid, Sevilla) working on very different research areas, all using Drosophila as a model system. Unfortunately, due to the brutal budget cuts that have taken place in the last years (a decrease of more than 30% in the public science budget in the last 2 years), a few groups using Drosophila as a model system could not attend the meeting. But most made it to be there (more than 40 research groups were represented) and made it clear that they are part of a very active and fruitful community that has lots to contribute to the global science and to society in general.

Topics discussed at the meeting covered several research fields including the analysis of the gene regulatory networks and signaling pathways underlying organ growth and regeneration, the emergence of collective behaviour during morphogenesis and organogenesis as well as evolutionary aspects to understand the generation of diversity. One of the major questions that was raised several times during the workshop is how organ size is controlled both in normal development and in disease. This question is being approached by different groups using a variety of experimental systems and from different perspectives. The group of Tano González (IRB, Barcelona) has a long-standing interest in understanding the basic principles underlying asymmetric cell division using neuroblasts as a model system and how failures in this process can give rise to malignant transformation. He presented novel results from his lab showing very dynamic patterns of gene expression during tomour growth. During neuroblast asymmetric division, Manuel Mendoza (CRG, Barcelona) is investigating how chromosome condensation adjusts to spindle length, a crucial process to ensure proper segregation that could be affected in malignancies. The control of tumour growth is also being studied by the group of Andreu Casali (IRB, Barcelona), who is using a model system for colorectal cancer by generating mutant clones for Apc and an activated form of Ras in the gut, while Manuel Calleja (CBM, Madrid) is studying cytoneme-mediated communication of tumour cells with their microenvironment. In the female germline, Acaimo González Reyes (CABD, Seville) is interested in the role of the physical environment in the control of germ cell proliferation and differentiation.

Using a different framework but asking the same basic question of how proper organ size is achieved, the groups of Antonio Baonza (CBM, Madrid), Ginés Morata (CBM, Madrid) and Florenci Serras (University of Barcelona) are studying the cellular and molecular mechanisms that regulate tissue regeneration in imaginal discs and how the balance between proliferation and differentiation is achieved in this situation. Ernesto Sánchez Herrero´s lab (CBM, Madrid) is also investigating how the final size of an organ is achieved and he presented data on how homeotic and sex-determination genes regulate the growth of sex-specific organs. From a more organismal perspective, the question of how the growth of different organs is coordinated in an organism to bring about well proportioned adult organs is being tackled by the group of Marco Milán (IRB, Barcelona), who reported a key role for bantam miRNA in both organ-autonomous and systemic growth. The control of systemic growth is very linked to the maintenance of the organismal homeostasis and this is being studied in the  group of Joaquín Culi (CABD, Seville) by analysing of the role of lipophorin receptors in the maintenance of the germ line, while the group of Rosa Barrio (CIC bioGUNE, Bilbao) focusses on how sumoylation regulates steroid hormone synthesis by regulating lipid intake in the ring gland and ovary and hence controlling animal size and viability.

Another important question raised in the meeting is how the collective behaviour of tissues emerges from the coordinated activity of individual cells. The molecular, cellular and mechanical basis of epithelial sheet movements is being investigated using a variety of experimental systems such as the embryonic epidermis, in Marta Llimargas’ lab (IBMB, Barcelona), who showed a role for the apical determinant Crumbs in cell shape and tissue organization. Nicole Gorfinkiel (CBM, Madrid) and Jerome Solon (CRG, Barcelona) are using Dorsal Closure to understand the interplay between cell activity and mechanics during morphogenesis. Collective cell migration is a process that also receives very much attention. Enrique Martin-Blanco´s group (IBMB, Barcelona) has undertaken a multi-scale analysis from signaling pathways to cell behaviour and tissue mechanics applied to the growth and expansion of the histoblasts nests of the abdomen. Lola Martín-Bermudo’s (CABD, Seville) lab is interested in cell migration and showed impressive movies of the collective movement of the follicular epitelium which depends on the composition of the extra-cellular matrix. The extra-cellular matrix is also important for both the formation of muscle-tendon junction and for the maintenance of muscle viability throughout adult life, as shown by Beatriz Estrada (CABD, Seville). Sara Ricardo (IBMB, Barcelona) is using the migration of the primordial germ cells to understand the complex interactions between the cells and their substrate for proper directed migration to occur. The genetic basis of cell migration, pathfinding and branching in both tracheal formation and axon guidance is being approached by the group of Sofía Araújo (IBMB, IRB, Barcelona). Jordi Casanova’s lab (IBMB, IRB, Barcelona) has been also studying tracheal formation for several years with the aim to understand the link between genes, cells and tissues. He presented new data showing the existence of a novel epithelial-mesenchymal transition pathway driven by the activity of the Serpent GATA factor that impinges directly on apico-basal polarity. How cell polarity influences signaling is being studied by Sonsoles Campuzano’s lab (CBM, Madrid) who showed data on how apico-basal polarity determinants controls intra-cellular trafficking and thus signaling in the follicular epithelium. Alberto Ferrús (Instituto Cajal, Madrid) presented novel data on the non-muscle functions of Troponin as a nuclear polarity marker.

The genetic basis of pattern formation and differentiation is being studied in different organs such as the wing imaginal disc where Jose Felix de Celis lab (CBM, Madrid) is identifying new genes involved in mediating the activity of the main regulators of the wing morphogenesis. In the nervous system, the group of Fernando Díaz-Benjumea (CBM, Madrid) is investigating the genetic combinatorial code that generates neuronal diversity and the mechanisms that control the entrance into quiesence of embryonic neuroblasts. Ana Carmena’s lab (Instituto de Neurociencias, Alicante) focusses on the function of Canoe, a key protein that integrates the different signaling pathways in the nervous system, while Francisco Tejedor (Instituto de Neurociencias, Alicante) studies the role of the gene minibrain in controlling the balance between cell proliferation and differentiation in the same system.

The molecular and biochemical mechanisms of trascriptional control during development are being investigated by Gerardo Jiménez´s lab (IBMB, Barcelona) who showed data on how Capicua, an effector of the RTK-Ras-MAPK pathway, represses its downstream genes. Natalia Azpiazu (CBM, Madrid) showed data from his group on the molecular basis of the transcriptional activity of the Hth/Meis family of proto-oncogenes and Fátima Gebauer’s lab (CRG, Barcelona) uses Drosophia to understand translational control. Whole genomic analysis presented by Montserrat Corominas and Roderic Guigó are starting to reveal unexpected chromatin arrangements at the level of house-keeping and developmental regulated genes, which may have strong implications for the understanding of epigenetics.

To understand how the architecture of gene regulatory networks controls organ architecture Fernando Casares (CABD, Seville) is developing software to quantitatively analyze protein expression levels with single nucleus resolution using confocal stacks in imaginal discs. A quantitative approach to infer the gene regulatory interactions has also been presented by Yogi Jaeger (CRG, Barcelona), whose lab is interested in understanding how the wiring of the gap gene network evolved accross different species of dipterans. Evolutionary approaches are also been undertaken by Xavier Franch-Marro’s lab (Institut de Biologia Evolutiva, Barcelona), who is interested in how the signaling pathways underlying organ formation evolve to generate morphological innovations during evolution. The study of gene regulatory networks that lead to organ formation done in James C.-G. Hombría’s lab (CABD, Seville) revealed that tracheal and endocrine organs arose through divergent evolution of a common segmentally repeated precursor. Finally, the genetic control of insect metamorphosis is being explored by David Martin (Institut de Biologia Evolutiva, Barcelona) with an emphasis in how this key process to insect success evolved accross the insect group.

Examples of translational research projects were presented by María Domínguez (Instituto de Neurociencias, Alicante), who is using genetically modified Drosophila as a tool to prescreen anti-cancer drugs in vivo and Mar Ruiz (CBM, Madrid), who has set up the Garland nephrocytes as a system to study the function of the filtration diaphragm in vertebrates. David Gubb (CIC bioGUNE, Bilbao) presented recent results on the function and specificity of the serpin family of proteins involved in the regulation of the immune response, that can have broad implications for the function of these proteins in humans.

On a different note, Matthieu Louis (CRG. Barcelona) showed data from his lab on how flies compute odorant stimuli and make decisions at the level of motor behaviour, in a very integrative project that uses genetics and optogenetics, and automated and high-resolution quantification of olfactory input and behavioural output.

The meeting has confirmed that the Spanish Drosophila community has very much grown in strength since it has first been established more than 40 years ago and that it has much to contribute to the global scientific project. There are now several active and innovative research hubs spread accross the whole Spanish geography showing that research in Drosophila is an extremely powerful tool to study basic biological processes that are at the basis of the advances in biomedicine. It would be of great interest if the Spanish government and policy makers understand that basic research in the fruitfly is one of the driving forces for biomedical reseach in Spain and lead them to design long-term scientific policies supporting and encouraging this global project.

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