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Calendar competition – And the winners are…

Posted by , on 20 May 2019

With over 10,000 votes cast, almost 6,000 people viewing the galleries and a new record for daily page views on the Node, we can now announce the winners of our inaugural calendar competition. We were blown away by the quality of the entries – 62 images of all kinds of cells, tissues and embryos. Check out the original post to see all the entries – as you’ll see, so many beautiful images missed out, and we’d like to thank everyone who took part.

So, category by category, here are the 12 winners who will make the final print calendar, and below them a full vote rundown (there were quite a few close calls!). We’re aiming to take the calendars with us to two upcoming meetings: SDB in Boston in July and the European Developmental Biology Congress in Alicante in October. Come grab one if you’re going.


 

Mammals

 

1st place: Light up

By Paul Gerald Layague Sanchez

(EMBL Heidelberg)

E14.5 mouse embryo labeled for cartilage (Sox9-GFP, in biop-SpringGreen) and vasculature (highlighter ink circulated by injection in a blood vessel, in mpl-magma). Vasculature “lights up” the embryo, including within the developing bones of the limbs. Image taken using a microscope kindly sponsored by Zeiss during the 2018 Embryology Course at the Marine Biological Laboratory in Woods Hole, MA.

 

2nd place: Human neuron

By Nicholas Gatford

(Institute of Psychiatry, Psychology and Neuroscience, King’s College London)

Super-resolution image acquired via structured illumination microscopy of a single developing human neuron ectopically expressing the autism risk gene neuroligin-4X with enlarged growth cones. F-actin is in green, HA-tagged neuroligin-4X is in magenta, doublecortin is in cyan confirming its neuronal identity, and the nuclear marker DAPI is in grey.

 

Zebrafish

 

1st place: Zebrafish head

By Oscar Ruiz

(Department of Genetics MD Anderson Cancer Center)

Transgenic zebrafish (Danio rerio) larva expressing red fluorescent protein in the developing mouth and olfactory epithelium. A subset of cells also express a construct that labels actin filament with green fluorescent protein. DAPI (blue) is used to label DNA in the nuclei of all cells.

 

2nd place: Zebrafish gills

By Philippa Carr

(Bateson Centre, University of Sheffield)

Developing gill vasculature in a 120h old zebrafish and also features the heart. This image was taken using lightsheet microscopy in two transgenic lines, one that marks the endothelial actin and the other marks the endothelial nuclei. After acquisition it was processed as a colour coded depth projection.

 

Vertebrate variety show

 

1st place: Alligator

By Daniel Smith Paredes

(Department of Geology and Geophysics, Yale University)

Alligator mississipiensis embryo at stage 13-14 immunostained against Myosin heavy chain showing the developing muscles and (red) and neurofilament labeling axons of nerves.

 

2nd place: Chicken embryo

By Laurel Yohe

(Department of Geology and Geophysics, Yale University)

Stage 35 chicken embryo, cleared and immunostained for DAPI (orange) and Pax3 (cyan) demonstrating the developing neural crest and spinal cord. Image was taken on the Nikon AZ-C2 macro-confocal with image analysis performed in Imaris. Image was taken in collaboration with Andrea Attardi at the Max Planck Institute of Molecular Cell Biology and Genetics during the Woods Hole 2018 Embryology course.

 

Drosophila

 

1st place: Drosophila ovary

By Yujun Chen

(Kansas State University Division of Biology).

*Yujun also wins the ‘Star of Instagram’ award for most-liked post (we posted all 62 individually from Development’s account!), and the image is the new profile pic*

Drosophila whole ovary stained for f-actin (Red), nuclei (Cyan) and actin (Green).

 

 

2nd place: Metallic flight

By Marisa Merino

(Department of Biochemistry, University of Geneva)

Drosophila mutant showing a decreased eye size compared to wild type. This line is not able to generate descendants with wild type flies.

 

Invertebrate variety show

 

1st place: Bobtail squid

By Martyna Lukoseviciute

(Weatherall Institute of Molecular Medicine, University of Oxford)

Live Hawaiian Bobtail Squid (Euprymna scolopes), stained with vital dyes (CellMask, LysoTracker and Hoechst) to understand its cellular and sub-cellular organisation during development. Blue is labelling cellular nuclei, green – cell plasma membranes and red – lysosomes that are important for cellular waste removal. This species is a candidate model organism that yet holds many answers to developmental biology questions, such as nervous system and eye development. The image was taken during the MBL 2018 Embryology Course with the confocal microscope provided by Zeiss. Animals were supplied by the cephalopod researcher Carrie Albertin.

 

2nd place: Hydractinia

By Indu Patwal

(Centre for Chromosome Biology, National University of Ireland Galway)

DIC and fluorescence image of Hydractinia male sexual (left) and feeding polyps (right) on a chitin bed. Chitin is shown in green. Noncycling cells probed with cyclin-dependent kinase inhibitor (CDKI) are shown in yellow, which are mainly in nematocytes, male gonophore, and gastrodermis.

 

Plants, Fungi and Choanoflagellates

 

1st place: Arabidopsis lateral root

By Robertas Ursache

(University of Lausanne, Switzerland)

The development of a lateral root in Arabidopsis thaliana. The sample has been cleared and stained with Calcofluor White to outline the cell walls and the green fluorescent nuclei represent a protein expressed specifically in the outer cell layer of developing lateral root.

 

Art and illustration

 

1st place: The yin and yang of developmental patterning

By Beata Edyta Mierzwa

(Ludwig Institute for Cancer Research and the University of California, San Diego, and www.beatascienceart.com)

This drawing illustrates the remarkable self-organization capacity of cerebral organoids that allows them to recapitulate human brain development in vitro. Each color represents a different type of cell, and the dorsal and ventral areas are separated by a defined boundary – like a yin and yang symbolizing the balance between distinct but complementary entities.

 

Full vote rundown

 

 

Mammals

 

 

Zebrafish

 

 

Vertebrate variety show

 

 

Drosophila

 

 

Invertebrate variety show

 

 

Plants, Fungi and Choanoflagellates

 

 

Art and illustration

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Research Lab manager in the Pourquie lab focused on the development of the musculo-skeletal system in vivo and in vitro

Posted by , on 15 May 2019

Closing Date: 15 March 2021

Job Location:

Brigham and Women’s Hospital, Development of the Musculo-Skeletal system / Pourquie Lab, Boston, MA, USA

 

Job Summary

The Research Lab Manager will assume a key role in the Pourquie lab (Brigham and Women’s Hospital, Pathology/Harvard Medical School/Genetics Departments) (15 to 18-person lab). The Lab manager works under the very general direction of Principal Investigator and participates in research involving up-to-date biological techniques in developmental biology and cell culture to investigate the mechanisms controlling the formation of the vertebrae and muscles during embryonic development.  Under general direction, performs non-routine and highly specialized experimental procedures that involve substantial “hands on” work and the ability to multi-task across various projects within the lab. Has day-today supervisory responsibility of laboratory operations and personnel.  Coordinates lab activities, composes and may present research reports, participates in design and modification of lab protocols and assist in grant data generation and writing.

 

Principal duties and responsibilities:

  1. Works independently with general guidance from the Principal Investigator.
  2. Independently performs routine biological experiments. Experimental techniques may include: protein biochemistry; cell fixation and basic immunohistochemistry/immunofluorescence; gene expression analysis such as quantitative real-time PCR, in-situ hybridization, molecular biology, standard mammalian cell culture techniques as well as isolation of primary stem cell cultures from animal tissues.
  3. Independently performs non-routine, highly specialized experimental procedures including in vitro direct differentiation of pluripotent stem cells, maintenance of pluripotent cell lines, microsurgery and gene transfer technologies in chicken and mouse embryo model systems, advanced molecular cloning, in vivo cell transplantation in mouse models.
  4. Performs confocal microscopy techniques and flow cytometry experiments, time-lapse imaging and live cell microscopy and analysis of resulting data using instrument software
  5. Performs advanced data analysis using advanced statistical techniques.
  6. Trains Lab staff in routine and specialized lab techniques
  7. Oversees and coordinates scheduling of lab procedures
  8. Oversees mouse colonies and coordinates the use of mice by other laboratory members
  9. Oversees and coordinates cell culture room operations (reagent supply and reagents testing, personnel training, maintains stocks, cell archives, organizes room cleaning)
  10. Oversees all lab supply and equipment, organization, purchasing and maintenance
  11. Oversees activities related to laboratory compliance with institutional health and safety regulations, such as proper inventory, storage, use, and disposal of radioactive and toxic substances and serves as the designated laboratory Safety Officer.
  12. Manages and supervises the day-to-day activities of the lab’s Technical Research Assistants (grades I or II)
  13. Coordinates lab resources utilization and material requests with other labs

 

Qualifications:

  • Master of Science in a biological science required, PhD preferred
  • Minimum 3 years’ hands-on experience in cell culture
  • Previous experience as a supervisor or manager
  • Experience with laboratory mouse colony maintenance preferred
  • Experience with embryonic stem cell or iPS cell culture preferred

 

Skills / Abilities / Competencies required

  • Strong organizational and scientific skills
  • Sound interpersonal skills, ability to constructively interact with the research team members
  • Excellent oral and written communication skills
  • High degree of computer literacy

 

Working conditions

  • Standard biosciences laboratory environment
  • Exposure to laboratory reagents, chemicals, and animal /human tissues under controlled conditions. Minimal risk when following established protocols and federal, state, local, and hospital guidelines

 

To apply to this position please send your resume and cover letter to Olivier Pourquie (pourquie@genetics.med.harvard.edu)

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Postdoctoral Position to study Morphogenesis in Embryonic Development and Human Diseases

Posted by , on 15 May 2019

Closing Date: 15 March 2021

An NIH-funded postdoctoral position is available in Jianbo Wang’s lab at the Univ. of Alabama at Birmingham. We study how shape forms during embryogenesis, and how aberrant shape formation leads to congenital birth defects. The process of shape formation is known as morphogenesis, and is regulated in part by the planar cell polarity (PCP) pathway. PCP is a unique signaling mechanism that coordinates cellular polarity and regulates dynamic, directional cell behavior. Our studies involve multi-disciplinary approaches including genetic, imaging, cell biology and biochemistry;  and use multiple model organisms including the mouse, chick and Xenopus. Our goals are to 1) uncover novel mechanisms and logic of PCP signaling; 2) elucidate the role of PCP in cardiovascular, skeletal and neural development; and 3) investigate how human PCP gene variants contribute to congenital disorders.

We are looking for highly motivated applicants with training in Developmental Biology, Genetics, Cell Biology or a related discipline. To apply, please email your CV, a description of previous research and contact information for three references to j18wang@uab.edu.

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The alchemy of an inspiring conference: a workshop reflection

Posted by , on 15 May 2019

This blog post is a reflection on the Company of Biologists-organized workshop on Chromatin-Based Regulation of Development that I recently attended at Wiston House, located in the countryside of Sussex in the UK.

 

Wiston House, Steyning, UK

 

To my mind, this workshop was the ideal of what a meeting should be. As a freshly minted assistant professor at the University of California, San Francisco, this workshop came at an excellent time for me to learn, glean inspiration, and extract advice.

 

A good conference is much more than the sum of its parts – the “parts” being the topics represented by the scientist attendees. By reading publications, you learn what experiments worked and hung together in a narrative. By hearing that work presented in person, you can infer the hunches or obsessions that drove the scientist to ask the question in the first place, as well as see the pieces of data that are forming the nucleus for the next phase of work.

 

A good conference provides an opportunity to rapidly survey ongoing work in your field. Through discussions and debates, you can learn whether your field has reached a consensus that a prevailing model consistently explains observations, or whether alternative explanations are being fomented. In this frame of mind, a new question that no one else seems to be asking might occur to you. Equally helpfully, you may discern whether a particular area is overpopulated and incorporate that knowledge to adjust your own project strategy. By assimilating all of this, you expand your knowledge base and learn by observing how other scientists think.

 

Mid-scientific debate in the library at Wiston House

 

At a good conference, you will forge connections with peers that may turn into friendships and collaborations in the future. You will interact with leaders in your field, gaining invaluable opportunity to pick their brains for career advice and to watch a well-honed scientific intuition at work. In doing all of this, you will have been doing the dreaded “networking”, too.

 

Taking a break for a hike “up the downs” (photo by @sudpinglay)

 

When it’s all over, you will return to your home lab armed with new ideas to test, with a new solution to a hurdle you have faced, or with new critiques from your peers to answer.

 

All of these features of the ideal conference were on display at this Company of Biologists workshop. The small size, intimate setting, and considerate pace of the meeting allowed for time to ruminate over exciting presentations and talk through ideas with other attendees. Early career researchers and established faculty were equal participants both in numbers and in the share of the conference program allotted to them. This was truly the most thoughtfully organized workshop I have ever attended.

 

 

 

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How the snail’s shell got its coil

Posted by , on 14 May 2019

Researchers from the Tokyo University of Science, Japan, have used CRISPR gene editing technology to make snails with shells that coil the ‘wrong’ way, providing insights into the fundamental basis of left-right asymmetry in animals. These findings were recently published in Development.

If you look at a snail’s shell, the chances are it will coil to the right. But, occasionally, you might find an unlucky one that twists in the opposite direction – as fans of Jeremy the lefty snail (https://en.wikipedia.org/wiki/Jeremy_(snail)) will remember, these snails struggle to mate with the more common rightward-coiling individuals.
This chirality (direction of coiling) of snail shells is an outward manifestation of left-right asymmetry: a phenomenon seen across animal evolution and extending to humans – your heart is (probably) on your left side, while your liver is to the right. But how does this asymmetry come about? Researchers from Japan, writing in the journal Development, think they now have a definitive answer – for one species of freshwater snail (Lymnaea stagnalis) at least.

Successfully applying CRISPR gene editing technology to molluscs for the first time, Masanori Abe and Reiko Kuroda (working at Tokyo University of Science, but recently relocated to Chubu University, Japan), have now made snails with mutations in a gene called Lsdia1, which had previously been suggested – but not conclusively proven – to be involved in snail shell coiling; snails without a functional copy of Lsdia1 produce offspring with shells that coil to the left, showing that this single gene is responsible for rightward- coiling. Surprisingly, the researchers could see signs of asymmetry at the earliest possible stage of development – when the snail embryo was just a single cell. Moreover, the mutant snails could be reared to adults, when they produced exclusively leftward-coiling offspring. According to Kuroda: “It is remarkable that these snails with reversed coiling are healthy and fertile, and that this coiling can be inherited generation after generation (we now have 5th-generation leftward-coiling snails). Further, these results may have an implication for snail evolution and speciation – given that left- and rightward-coiling snails probably wouldn’t interbreed.”

 

Knocking out one gene in the snail Lymnaea stagnalis reverses shell coiling. In contrast to the wild-type dextral snail (right), a CRISPR-created snail shows sinistral coiling (left). Credit:
Dr Hiromi Takahashi of the Kuroda laboratory.

 

It’s still not clear how Lsdia1 might control left-right asymmetry: the gene encodes a formin, a protein that is involved in regulating the cell’s internal skeleton, but more work is needed to understand how this influences the cellular behaviours that control handedness – which is something Kuroda and her colleagues are actively working on. But given that genes like Lsdia1 are found throughout the animal kingdom, similar mechanisms for controlling left-right asymmetry could be at play in other species – including our own. As Kuroda says: “Although diverse mechanisms have been proposed for different animals, we think a unified mechanism, involving formins and cellular chirality, is probable”. So while it may seem a big leap from snail shell coiling to human left-right asymmetries, it’s possible that future studies on how Lsdia1 works in snails might eventually help us understand why some babies are born with their heart on the right (which is of course the wrong) side of their chest.


The development of CRISPR for a mollusc establishes the formin Lsdia1 as the long-sought gene for snail dextral/sinistral coiling

Masanori Abe, Reiko Kuroda

Development 2019 146: dev175976 doi: 10.1242/dev.175976 Published 14 May 2019

 

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the Node Calendar competition – vote here, vote now!

Posted by , on 14 May 2019

*Voting is closed and winners have been announced!*


 

Our call for images to fill our 2019-20 calendar was met with an amazing response – 62 entries showcasing the diverse beauty of developmental biology. Now it’s time for you vote for the 12 that will make it into print.

Because we want a range of organisms and styles in the calendar, and because picking 12 favourites from 62 is not the easiest task, we’ve decided to split the voting up into categories. Turns out 12 into 62 doesn’t go so well, and some categories were better represented than others, so we ended up with the following:

 

  • Mammals (vote for 2 out of 10)
  • Zebrafish (vote for 2 out of 8)
  • Vertebrate variety show (vote for 2 out 10)
  • Drosophila (vote for 2 out of 11)
  • Invertebrate variety show (vote for 2 out 11)
  • Plants, Fungi and Choanoflagellates (vote for 1 out of 7)
  • Art and Illustration (vote for 1 out of 5)

 

The cut offs are a little arbitrary but it’s the best scheme we could come up with. Inevitably, many beautiful images are going to miss out, but we hope the selection stands alone in showcasing the aesthetic side of research.

The pictures are arranged in galleries – click to expand the image and see the caption (there’s also a link to see the image full size). Below the galleries are independent polls to pick your favourites from each section. Both the galleries and the polls are arranged alphabetically by creator, and the poll text is the same as the file name (e.g. ‘Blin. mESC micropatterns’) which you can see below the caption. Please just vote once (well, twelve times!) – polls are set up to stop repeat voters by cookie.

Voting closes on Sunday 19 May 23:59 GMT

 

You can also let us know what your overall favourite is in the comments. Happy voting.

 

Mammals (Mus and Homo)

 

 

Please pick your favourite images

(please remember to pick 2)

 


 

 

 

Zebrafish

 

 

Please pick your favourite images

(please remember to pick 2)

 


 

 

Vertebrate variety show

 

 

Please pick your favourite images

(please remember to pick 2)

 


 

Drosophila

 

 

Please pick your favourite images

(please remember to pick 2)

 


 

Invertebrate variety show

 

 

Please pick your favourite images

(please remember to pick 2)

 


 

Plants, Fungi and Choanoflagellates

 

Please pick your favourite image


 

Art and illustration

 

 

Please pick your favourite image

 


 

Thanks for voting – if you made an error, just email aidan.maartens@biologists.com and we’ll correct the numbers!


 

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Echoes of “Chromatin-Based Regulation of Development” workshop OR “to TAD or not to TAD”?

Posted by , on 14 May 2019

The non-profit publishing groups can make a real difference

The very best part of being a scientist is cracking mysteries of the universe and what is in it. The second best thing about this profession, in my opinion, is being part of a scientific community. Conversations, conferences, workshops, collaborations, networking, support and constant inspiration from one another serve as a magic glue that keeps us together and motivates us to keep pushing the boundaries of the unknown. A perfect example of fostering a scientific community is the astounding job done by The Company of Biologists. As you may know, The Company of Biologists is a not-for-profit publishing organisation dedicated to supporting and inspiring the biological community. After attending the truly inspiring and excellent workshop on ‘Chromatin-Based Regulation of Development’ this April, I now genuinely understand the differences between profit-oriented and community-oriented publishing groups. The Company of Biologists is on a profound mission to give back to the community, for example, by organising workshops that aim to bring together scientists who would normally rarely meet, across the globe from the same or different fields. This holds real power and serves an important purpose for both scientists individually and science on the whole. I would like to thank The Company of Biologists for creating such great initiatives and also share my experiences of this fantastic workshop from an early career scientist’s view (I’m currently a final year PhD student in Tatjana Sauka-Spengler lab in the University of Oxford).

 

The highlights of the ‘Chromatin-Based Regulation of Development’ workshop

The workshop was organised by Benoit Bruneau (Gladstone Institutes, UCSF, USA) and Joanna Wysocka (Stanford University, USA) for 30 participants (17 invited speakers and 13 selected early-career researchers like me). The entire workshop was fully funded by the Company of Biologists: even the selected early-career researchers did not have to pay for attendance, which – let’s be honest – is somewhat unheard of! It was situated in a beautiful English manor house, Wiston House, in the South Downs National Park on the south coast of England. The venue, including my room, was so gorgeous that for four days I got to feel a little bit as if I belonged to the Royal family.

The purpose of the workshop was to bring together scientists from different places, expertise and career levels, yet it felt as if it was a non-hierarchical environment, where all scientists had an opportunity to contribute to all aspects of this great workshop equally. For instance, each one of us, no matter who, a PhD student or a professor, had an opportunity to officially present their research and answer questions for 30 minutes followed by an informal discussion and further questions during coffee breaks or at the cosy Wiston house bar. Also, dinners were organised superbly, where we were randomly allocated a different seat every night, getting a chance to speak with different scientists. This way, I got to sit and connect with scientists, such as Joanna Wysocka or Stefan Mundlos, that I would have been most likely too shy to sit next to in a ‘real-life’ setting. Overall, it was very nice to not only discuss scientific questions but also to get advice for future career steps and to talk about life-work-balance, women in science problems and other relatable questions.

Hiking break around the Wiston house grounds with the participants before the evening session.

 

The workshop topics

The workshop consisted of nine sessions. The first two sessions focussed on 3D genome regulation during various developmental processes – from embryo patterning to limb development to synthetic Hox cluster building. During the workshop, we extensively scrutinised whether topologically associating domains (TADs) are actually central for gene regulation or rather if they only play genome-packaging/replication roles. Surprisingly, a lot of presented data challenged the importance of TADs for gene regulation (as nicely and critically reviewed in another participant’s – Roel Neijts’ – Node post (https://thenode.biologists.com/meeting-report-chromatin-based-regulation-of-development-an-excellent-workshop-by-the-company-of-biologists/events/)).

Other sessions delved into enhancers, their sequence variations and gene regulation during early development. We got to learn how histone variants at enhancer sites can play a predominant part in tissue-specific gene regulation and when misregulated can lead to severe cranial facial syndromes. Or how some enhancers are critical for sex determination and how knocking them out can lead to sex reversal despite the inherited X or Y chromosome combinations. Overall, the emerging trend indicated that active enhancers usually stay active despite TAD perturbation and that their close proximity to promoters is, most of the time, enough to drive correct gene expression; by contrast, inactive enhancers – even when they are ectopically brought to promoters – almost never get ‘turned-on’. Therefore, maybe chromatin marks rather than chromatin confirmation are more instructive when it comes to gene regulation?

The organiser Joanna Wysocka is opening our debate evening on questions: ‘Is chromatin topology important for gene expression?’ and ‘Does phase-separation enable gene regulation within a crowded nucleus?’

 

We also looked into how transcription factors (TFs) regulate chromatin dynamics and nucleosome phasing. For instance, how do TFs work together with morphogens or in a combinatorial TF manner to create certain types of chromatin that correspond to tissue-specific gene expression? Or, how are they capable of forming liquid-like aggregates allowing a local increase in the concentration of scarcely available TFs in both plants and animals? Undeniably, the topic of phase-separation was extensively deliberated during both the talks and our evening debate. It seems that for us, biologists, this subject is still somewhat of a phenomenon when it comes to gene regulation. However, a steadily increasing number of experiments show that phase-separation might play very important roles, as illustrated by heterochromatin formation driven by HP1a phase-separation or polycomb body aggregation, which is important for gene repression and even formation of a repressive 3D chromatin.

 

Food for thought

Lastly, this brilliant workshop taught me a lot not only about the different shapes and shades of chromatin but also about its formation, dynamics and roles in developmental gene regulation. It was rather eye-opening to see how important it can be to learn from experts in a completely transparent and relaxed environment, where no one was afraid of sharing unpublished data, hypotheses and ideas. This was truly freeing and inspiring, and I could start shaping my own ideas and endorse a different way of thinking about my own research and future directions. Different emerging methods of studying chromatin were brought into the light of this workshop, e.g., not only looking at chromatin marks and accessibility using molecular biology methods , but also trying to visualize chromatin by employing different new imaging tools (after all – seeing is believing!) or turning to biophysical principles of embryo development and underlying chromatin-mediated gene expression dynamics. Taking even one step further, towards Feynman’s school of thought (“What I cannot create, I do not understand”), we got to hear about the importance of synthetic systems to generate in vitro chromatin, engineer chromatin contacts using optogenetics tools or produce synthetic embryo-like structures (e.g. gastruloids) in order to genuinely understand the basic principles and rules of many yet unanswered questions of chromatin-based regulation of development. As you might have already thought, usually there is no perfect single methodology to solve complex biological puzzles, and only collaborations between different fields can facilitate the quality and speed of putting all the pieces of such puzzles together. Importantly, workshops like this one that I had a privilege to attend bring experts from different fields together, which definitely accelerates the progress of science and inspires a lot of young scientists to tackle even the most complex problems of our universe in new ways.

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Meeting report of the Cambridge Fly Club Symposium – Past, Present and Future of Drosophila Research

Posted by , on 10 May 2019

By Ghislain Gillard, Maria J. Gomez Lamarca, Robert Krautz, Rosa Park, David Salvador-Garcia, Yara Sanchez-Corrales and Jelle van den Ameele

 

On the 28th of January, the Cambridge Fly Club held its very first Symposium in the beautiful environment of Wolfson College, Cambridge, UK. This meeting, titled “Past, Present and Future of Drosophila research” was supported by a small meeting grant from the Company of Biologists and brought together 130 scientists, mostly from Cambridge, UK, who work with the fruit fly Drosophila melanogaster.

The Cambridge Fly Club is a group of PhD students and postdocs who organise a couple of scientific meetings with pizza and drinks every other month to maintain a positive dynamic within the friendly and collaborative fly community in Cambridge. However, this year, we had a special anniversary to celebrate, because 25 years ago, Andrea Brand and Norbert Perrimon published their landmark paper in Development describing the Drosophila GAL4 system (Brand and Perrimon, 1993). The GAL4 system enables targeted gene expression in virtually any cell type and has facilitated many breakthrough discoveries in physiology and developmental biology.

 

A modern woman’s guide to fly design

We were very lucky that Andrea Brand (WT/CRUK Gurdon Institute) agreed to give a plenary lecture about how she came to develop the GAL4 system with Norbert Perrimon. For many of the attendees, this talk was the highlight of the symposium, and for some of them even “the best talk they had ever seen”. Andrea worked on yeast transcription as a PhD student and was then a postdoctoral Fellow in Mark Ptashne’s lab at Harvard University before joining the Perrimon lab for a second postdoc. The Ptashne lab were studying the yeast transcriptional activator GAL4 and found, surprisingly at the time, that GAL4 could activate transcription in organisms other than yeast. Inspired by this knowledge and by a seminar given by Walter Gehring on his lab’s unpublished work on lacZ enhancer trapping, Andrea realized that substituting GAL4 for lacZ would enable cell fates to be manipulated in vivo, rather than merely labelled. To put theory into practice, Andrea moved to the Perrimon lab in early 1988, bringing her knowledge about yeast genetics and molecular biology together with Norbert’s expertise in Drosophila genetics. The ease of hopping the GAL4 within the Drosophila genome, through P-element transposition allowed to capture the expression pattern of new uncharacterized enhancers and resulted in large numbers of GAL4 lines being generated quickly. Andrea got her first result with the GAL4 system in September 1989 – she even showed us the page from her lab notebook!

Development of the GAL4 system was the result of hard work, dedication and resilience and even a bit of luck: Andrea was introduced to Norbert by a chance meeting with a yeast colleague, Fred Winston. Andrea gave a great and positive message for all young scientists in the audience and inspired us with some of her creative poster designs – “a modern woman’s guide to fly design” did stick in our minds! Her message was to follow your dreams in spite of the inevitable hurdles that come your way.

 

Collaborative workshops

The plenary lecture was then followed by several high-quality workshops, delivered by leaders in their respective fields and mostly focused on transformative technologies from the past, present and future.

The different aspects of CRISPR/Cas9 in flies were nicely introduced in a very popular workshop by Simon Bullock from the MRC Laboratory of Molecular Biology. He talked about how to use CRISPR-Cas9 to generate mutant alleles, tag proteins and even perfom tissue-specific gene disruption. His talk was full of practical tips and advice, including potential pitfalls and how to recover the desired mutation. In a workshop on the art and history of genetic screens, Daniel St Johnston from the WT/CRUK Gurdon Institute presented an impressive overview of the various strategies to perform forward genetic screening, illustrating every approach with a historical landmark paper. Which mutagen to go for – EMS according to Daniel, or X-rays (without the protective plastic cover) according to Adelaide Carpenter – remains an unsolved question though.

Three other workshops were set up as collaborations between scientists from different institutes across Cambridge. Ben Sutcliffe (MRC Laboratory of Molecular Biology), Edward Allgeyer and George Sirinakis (WT/CRUK Gurdon Institute) gave an overview of imaging Drosophila tissues using three different advanced light microscopy techniques: single molecule localization microscopy, STED, and light-sheet microscopy. Considering the notorious difficulty of applying super-resolution methods to thick biological samples, Ed and George generated a lot of interest into how they custom-built 4Pi-SMS and STED microscopes for imaging different Drosophila tissues such as the ovary. Equally exciting was Ben’s imaging setup for capturing live tissue-dynamics of Drosophila embryos and larval salivary glands on a custom-built light-sheet microscope.

Alex Whitworth (MRC Mitochondrial Biology Unit), Cahir O’Kane (Department of Genetics) and Hansong Ma (WT/CRUK Gurdon Institute) convinced us that there is now a critical mass in Cambridge to study mitochondria in fruit flies. They introduced us to impressive and creative usage of powerful fly genetics to study mitochondrial inheritance and explained some exciting new discoveries with direct implications for neurodegenerative diseases. Finally, Greg Jefferis (MRC Laboratory of Molecular Biology), Matthias Landgraf and Marta Costa (Department of Zoology) teamed up to show that today’s high-level connectivity between Drosophila researchers had striking parallels in the Drosophila brain, whose neuronal networks they study with state-of-the-art techniques and powerful computational algorithms.

All the data, interpretations and scientific excitement that come from these technologies have to be shared of course. One platform that is widely used by the fly community is FlyBase, and Steven Marygold provided a very practical overview of how to perform large-scale queries in FlyBase. However, we all still like to publish our findings as a story, in the form of a journal article. Katherine Brown from Development, therefore, provided us with some very useful tips to make this actually happen – even the fly paper she published herself in Development 16 years ago turned out to offer room for improvement! She also generated new data for this symposium, summarising the success of Drosophila papers as opposed to other model organisms. These are more thoroughly discussed in her own recent blogpost.

 

A bright future for Drosophila research?!

To end this wonderful afternoon, Michael Akam, Andrea Brand, Cahir O’Kane, Katja Röper, Benedicte Sanson and Daniel St Johnston wholeheartedly joined in the game of discussing the future of Drosophila research. Young researchers clearly heard that it is not the model that makes great research, but the questions you ask. The powerful genetics, the possibility to study cell biology within a living organism, the emerging tools to study behaviour, or the relatively cheap maintenance of flies are only several of the many reasons why Drosophila will remain an important research model in the future. One reason to work with Drosophila was not discussed by the panel though: it makes you part of a wonderful, generous and vibrant community. Today’s symposium was a warm celebration of this great community.

This meeting has been organised thanks to the kind support of the Company of Biologists with several other sponsors which can be found together with the program of the event here.

 

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Publishing Fly Research

Posted by , on 9 May 2019

Back in January, The Cambridge Fly Club held a symposium to mark 25 years since the publication of the famous Gal4/UAS paper (Brand & Perrimon, 1993 – published in Development); the organisers have posted a meeting report here. As part of this symposium, the organisers asked me to give a talk on ‘Publishing Fly Research’. Particularly given that I worked with Drosophila in Cambridge as a research assistant and PhD student and attended the odd Cambridge Fly Club talk back in the early 2000s, I was more than happy to oblige, though I wasn’t initially sure what I was going to talk about – surely publishing fly research is just like publishing any research?!

But I decided that I wouldn’t just trot out my ‘standard’ publishing talk, and that instead I’d try and take a look at the publishing landscape for the fly community, and at how it’s changed since the publication of that landmark paper. Some of the data I gathered surprised me, and given that the audience seemed to find my insights useful, I thought I’d (somewhat belatedly) share them here. I also hope that this post will be useful beyond just the fly community, though I’ve not crunched the numbers for other systems.

So, what I looked at was the number of fly papers published over recent decades, and where they were published, and compared this to the number of mouse papers (representing the most popular vertebrate model system) and total papers. I also looked at citation rates, as well as at submission rates to Development. An important caveat: my analyses are very crude, and are based on keyword searches in PubMed, Web of Science and Development’s own submission system. For certain there are both false positives and false negatives in the numbers, but hopefully the trends still hold.

Looking over the past 35 years, it’s clear that publishing output has increased dramatically, and fly research has more than kept pace with this, ramping up massively in the 90s before plateauing in recent years.

But what about the influence of the fly field? Using papers published in Cell, Science and Nature as a (very imperfect) proxy for how ‘hot’ a field is, you can see that we hit ‘peak fly’ in the early 2000s, and the numbers of fly papers published in those journals has declined since then.

Incidentally, we see a not dissimilar trend in Development.  So where are fly papers being published? Back in 1993, the top venues for Drosophila research were Development, PNAS and Genetics. In 2018, it was eLife, Scientific Reports and PLoS Genetics; the most popular journals in the early 90s still make the top 10, but have been pushed down the pecking order primarily by large, broad scope OA journals (PLoS One and Nature Communications completed the top 5 in 2018).

It’s also the case that fly papers aren’t as well cited as mouse papers. I didn’t have access to historic citation data, but for publications in 2015, the average fly paper in the CNS journals cited half as well as the average mouse paper. The differences aren’t this dramatic for Development papers, but they are still there. And I think this is largely to be expected – the mouse community is larger than the fly community, so it’s natural that those papers will get more citations. Plus, I suspect a fly paper is much more likely to cite mouse work than the other way around – given the current ecosystem that values (perhaps overly values) mammalian and translational relevance.

So is it getting harder to publish fly papers? Looking at submission and acceptance rates in Development over the past 10 years, it seems that what has declined is submission rate – fly papers submitted to us are just as likely to be published as they were a decade ago, and they’ve got an above-average acceptance rate.

We just don’t see as many papers submitted to us as we used to (2017 submission rate was 60% that of a decade earlier). Whether this reflects changing journal preferences of authors, or a decline in the volume of Drosophila developmental biology papers, I can’t say. But I think it’s fair to argue that fly work doesn’t have an overly hard time with us.

I was also asked to comment in my talk on how fly researchers can maximise their chances of getting their work published and seen by a broad audience. It’s important to state from the outset that – at Development at least – fly papers are treated just the same as any paper: what we’re looking for are studies that advance our understanding of developmental processes, or report techniques or resources of broad interest to our community. We don’t need translational relevance and we don’t need you to replicate or confirm your findings in another system. But we are looking for papers that we think will be of interest beyond a small group of researchers in a particular area, and it’s helpful if you as authors can make it clear where that interest lies. This is important not only to get your paper past the editor and referees, but also to make sure it gets read once it’s published. Remember that the vast majority of people who come across your paper will only read the title. A small proportion might click through to see the abstract, and even fewer will go on to read the full paper. So, while I’m never going to advocate overselling a paper, it will help to make clear the broader context up-front, and make the title and abstract appealing to non-fly people.  Avoid fly-specific jargon and gene names (refer to E-cadherin, not shotgun!), and help the non-aficionados to realise the potential link to their own work.

Concrete examples are often more helpful than generic advice. So, and to avoid embarrassing anyone but myself, I went back and looked at my own very first paper – which I’m proud to say was published in Development. But looking at it now, the title and abstract fail to follow most of the advice given above. Just before my talk, I had a quick go at pulling the abstract apart and rewriting with my editor hat on. My new version is far from perfect, but hopefully it serves to exemplify the points I’ve made – scroll through the images below to see the first version, its flaws revealed, and a few little rewrites that at least start to make it more accessible. The title isn’t great either in terms of accessibility, though I remember Matthew and I agonised over the wording. If I had the chance again, I’d go with a simpler version – something like “Egfr signalling regulates ommatidial orientation in the Drosophila eye”. I fear the word ‘ommatidial’ would put most readers off immediately, but it’s hard to avoid – suggestions in the comments please!

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You focus on the science, we focus on the logistics

Posted by , on 9 May 2019

The Company of Biologists (Development’s not-for-profit publisher) is currently seeking proposals for Workshops to be held during 2021.

The Workshops provide leading experts and early-career researchers from a diverse range of scientific backgrounds with a stimulating environment for the cross-fertilisation of interdisciplinary ideas. The programmes are carefully developed and are intended to champion the novel techniques and innovations that will underpin important scientific advances.

 

Workshop proposals should take into account the following points:

  • Proposals should focus on cutting-edge scientific research in topic areas that are new, novel and not covered by traditional conferences.
  • Proposals that concentrate on emerging or cross-disciplinary themes are particularly encouraged.
  • Organisers should be experts in their field, with sufficient standing to attract world-class speakers and attendees.
  • Proposals should indicate how the Workshop will contribute to establishing new collaborations or research directions.
  • Each Workshop will consist of 30 delegates to include 10 early-career researcher places to be applied for and proposers should ensure diversity in the proposed attendee list. You will need to propose 20 speakers (but they don’t have to be confirmed).

As the scientific organiser your involvement will be focused on the science. We will undertake all of the logistical arrangements, liaise with the venue, organise speaker travel, help with arranging the programme and fund the meeting.

The deadline for proposals is  31 May 2019

Apply here:

biologists.com/workshops/propose-new-workshop


If you want to find out what workshops are like you can read two recent Node posts from early career participants:

 

Meeting report: “Chromatin-based regulation of development”, an excellent Workshop by the Company of Biologists
By RoelNeijts

 

Reflections on the ‘Evo-chromo’ Workshop (November 2018)

By Alexander Blackwell and James Gahan

 

 

Or watch the following videos:

 

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