We are looking for a POSTDOC to join our EVODEVO-GENOMICS lab in the University of BARCELONA.
Our lab studies the chordate model Oikopleura dioica to better the impact of gene loss on the evolution of gene regulatory networks. In particular, our research focusses on heart development, long-non-coding RNAs and de novo genes. Click here for a tour “A day in our lab” posted in The Node
Recently, we have also engaged a new EcoEvoDevo line investigating how mechanisms of development in marine embryos respond to climate change, including biotoxins derived from algal blooms. Click here for a tour on this new EcoEvoDevo adventure.
Our approaches include single-cell, RNAseq, Embryo microinjection, RNAi, Confocal-Microscopy, Bioinformatics, population genomics and soon CRISPR
Marie Skłodowska-Curie Individual Fellowships | Postdoc Call ID: H2020-MSCA-IF-2020
Open April 8th – Deadline September 9th 2020. (for University of Barcelona internal procedures, the application forms should be ready by the end of July)
CONTACT: Interested postdoc candidates, please send an email to Cristian Cañestro (canestro@ub.edu) ASAP, including a brief letter of interest, a brief CV, including list of publications with their impact factor and quartile, and technical skills (specially those related with our approaches) all together in ONE single pdf file.
This year I had a unique experience arising from my PhD – 2 weeks giving training in Nigeria, by invitation of Prof. Amos Abolaji from the University of Ibadan. Amos established one the first Drosophila labs in Nigeria in 2014, and in 2017 he co-organized workshop with DrosAfrica – a charity I collaborate with and that you should check out. I met him after we invited him to our EMBL PhD symposium in 2018. He kindly invited me to be a trainer at a Drosophila workshop he was organizing in Abuja in March last year, and to visit his lab in Ibadan too – to do embryo collections and stainings together, but also to prepare science outreach activities and visit two schools. In this article, I am going to share my experience and perhaps convince you to take on a similar adventure too.
Warm weather, warm hearts
When I got off the plane, which arrived to Lagos at 9pm, I didn’t know what to expect. It was hot, really hot! It stayed like that for the two weeks: we had on average 40-degree days, sometimes with a sensation of more. Amos was there to pick me up, dressed in traditional Yoruban clothes. My first impression of Nigeria remained loyal to what I would experience the following two weeks: very warm weather, very colourful attires, very warm and joyful hearts. Also, it is loud, there is always sound…In fact, when I returned home, one of my strongest impressions was that Heidelberg felt extremely quiet even though I live in the centre, which can be quite noisy. The Yoruba language sounds very musical – I learned a bit but wish I had learned more. I stayed for 9 days at the University of Ibadan (UI) and 5 days in Bingham, near Abuja. It is important to note that Nigeria is very big and multiculturally diverse, so what I share mostly reflects what I witnessed more closely in the South West region. I was the only visitor for a week, and, on my 7th day there, Dr. Alex Whitworth joined. Alex is a group leader at the MRC Mitochondrial Biology Unit in the University of Cambridge. It was great to experience both ways: all the new things you discover on your own, fully immersed, but also having someone from a (more) similar background to share experiences with. Alex was an incredible travel buddy to whom I am super grateful, and it wouldn’t have been the same without him; he also showed me that PIs can be cool travel buddies too! Finally, I had heard before going that food was spicy. Well, food is really spicy, and portions are very generous.
No excuses
Abolaji lab members in the lab, Bukola (left) is taking care of the flies
The Nigerian scientists I met had a constant mindset of “no excuses”, which comes from trying to overcome lack of resources with perseverance and creativity. This was not entirely new to me. In Portugal – where I come from and where I started working the bench – there is also this attitude. We had to plan seriously and we would coordinate with neighbouring labs to make sure resources were used to the maximum. At EMBL the conditions are very different, as we are quite wealthy and I would say a lot of people (including myself) are spoiled. There are a lot of things we don’t have to worry about such as preparing buffers, animal diet, washing our glassware etc.
We have the tendency to believe that science is objective and therefore democratic. But science is made by humans, and the socioeconomic context plays a huge role in the opportunities people have to realize their potential. If I felt a resource gap after travelling 2000 km between Portugal and Germany, this was even greater with the 6700 km between Heidelberg and Ibadan. I am not talking about not having fancy equipment. I am talking about, for example, not having constant power supply. What does that imply? It implies that you need to spend so much more time caring for the animals – flies in this case – which would be happier less 10-15 degrees Celsius of heat. It implies that you might have to run experiments until 5am because electricity is more stable during the evening. I met students who literally did this. And these students often face overscrutinity of their research credentials by recruiters in US/EU institutions, without taking into account the context and resources in place. Excellent people who dream about great experiments to their bold hypotheses, but sometimes cannot perform these tests with what is available to them. But still, they say “no excuses” – they are very creative to always find a way to improvise. This was true both for the Abolaji lab in UI and also the Bingham workshop participants I met in Abuja. I had heard Amos talk about the lack of power supply when he visited EMBL, but these are things you have to see for yourself to really grasp it. It is important, for the less aware, not to confound excellence gaps with resource gaps. And importantly, in Amos’ lab they share a lot of their equipment with other labs in the department. Since they have a KVA inverter to make up for power shortages, they even share power sockets: I often saw visitors coming in just to use their laptops and plug them in or charge their phones. This contrasted a lot to me with what I have seen in some Western labs, sometimes in the same institute, not wanting to share machines or reagents.
Adapting to your context
The culture I am used to doing science & science outreach in (from my experience in Portugal, UK, Denmark and Germany) is different from the culture of Nigeria. Again, this was not my first cultural shock, as I experienced it by moving abroad, first to the UK and then to Germany. Even after almost 3 years in Germany, I still struggle to adapt to some things. I also had been to Africa before, but it had been 10 years since I was there last, and this time it was for work, not vacation, and on my own, not with my family.
I love making plans and scheduling things to the detail. I am not super punctual, but with African time, there was never a dull moment. Even after some days of realizing that the pace of life was different, our brains are so wired in habits that Nigeria found ways to surprise me everyday. And I think that is great! In EMBL, if a seminar is at 1pm, it starts latest at 1.05pm. In Portugal, the lights of the amphitheatre would probably still be off at 1.05pm, and the audience joins around a quarter past. I felt that in Nigeria it was even more flexible. But this also needs to be put into context. Sometimes I was surprised by some breaks during the middle of the day, but it made sense because we experienced such hot weather (hot even for Nigerians themselves!), that it made more sense to continue going after it cooled a bit off in the evening, and we could stay until late. We made it to a domestic flight after arriving to the airport 15 minutes before departure, which was quite an adventure for me, but the friends I made there assured me that there usually is no “African time” for flights! In terms of planning, I would just say that no amount of planning is too much!
Amos in my first day in Ibadan, when he showed me his lab
I was used to certain health and safety measures from Europe, for example for dealing with chemicals. Guess what, if you don’t have many resources, it is hard to handle chemicals with such care. For me that was initially quite a shock, but eventually that shock grew into respect of the scientists I met who have to make much more sacrifices, including health and safety ones, to carry on with their experiments.
For me, the biggest lesson was that it takes more than ‘adapting’ to fully learn and grow from such an experience. You can go along new circumstances but still be making judgements on your mind, rejecting the new reality because it is done different from what you are used to. It is the jump from that to accepting and embracing it that makes all the difference. If I could go back in time, I wish I had resisted change less in my mind and had learned to accept it quicker, because without judgement you can live better in the present moment and make the most of it. Still, my new friends and fellow students there say that I adapted quite well! They would say – and this is a phrase everyone uses all the time, you just need to make eye contact with someone and you will hear it – “well done”.
Adapting to your audience
I was also faced with cultural difference in how to do outreach. And I remembered the motto “Adapt to your audience”. Instead of resisting different ways of doing it, I realized that the local way is probably the most effective, because the audience is local too. And I believe this goes beyond science communication. If we want to contribute to scientific capacity building, we cannot think we can turn up somewhere and just impose the way we are used to doing it. Again, the contexts are so different, how could there be a one size fits all approach? Regarding the school visits, it was great that these were made as team with the Abolaji lab, who taught me a lot about how to use flexibility and improvisation and also about approachability skills with kids. As curiosity, I was surprised that every single lab member out of 6-7 that came for these visits were natural talents with kids. How come not even one was an odd one out like me? I love doing outreach but I feel very shy. In the Nigerian context, besides having big families of 3+ siblings, the big religious influence means most are used to dealing with kids and to passing on (other types of) information to them. In fact, their deep religious practice makes them great storytellers, which is a key skill for science communication. This was also a great lesson, since we can antagonize science and religion without looking into the full picture.
Kenny and Ona-ara with primary school pupils from Ibadan
Outreach for development
Being involved with DrosAfrica – which wants to use the power of Drosophila to empower scientists all across Africa and has plans underway to build a big new institute – and looking up initiatives of scientific capacity building, I didn’t quite realize until being there how relevant outreach and science communication is in this context too. I always thought that there was so much to build for the research practice per se, that I didn’t realize I was putting outreach in a “bonus” category. But the way outreach is intricately involved in research is truly universal and outreach shouldn’t be neglected by the pressure of building core resources in labs. After all, we should spark interest in the young and spread science to society to help strengthen the developing scientific structures. So, I would like to encourage professional science communicators to pay it forward and embark on similar exchanges and visits too. Take your expertise where it can be so valuable and I guarantee you will walk home having learned a lot of new things too. I wrote specifically about my school visit experience in the EMBL School Ambassador website and you can check the EMBL-Nigeria pen pal project I started with my colleague Rafael Galupa in our blog.
Combating imposter syndrome
Me teaching in the Bingham workshop
As a PhD student, I strongly felt imposter syndrome when I was invited to train and teach, and that it was a big responsibility and investment for the little amount of knowledge I felt I could pass on. But I realized two things:
Even if you have less experience than a professor, you have a relatability factor that has great power speaking to young people like you.
I didn’t realize how many tools I have gathered from different experiences, and I was surprised to be able to go back and pick them up to share – such as a model used for a school visit or a draft structure a friend once sent me for a motivation letter I had to write. For me this underlined the interconnection of my life experiences and reminded me the hidden value of subtle things or experiences you don’t think about often anymore.
I also learned that the most effective way to contribute to scientific capacity building is to collaborate – meaning visiting, sharing expertise, sharing grants together and sharing or exchanging students. Finally, even if I am shy to admit it, I must say that I left Germany with the mindset that I was going there to teach. I was excited about this new experience, but I only realized after I arrived, that I was also going to learn A TON. And, for sure, I brought more with me than I left there. I swear that this did not come from arrogance but from naivety. If I had focused earlier on how much I would also learn, maybe I would have worried less about my imposter syndrome.
A final message
“Nothing in life is to be feared, it is only to be understood. Now is the time to understand more, so that we may fear less.” Marie Curie
Kenny, Bolaji, Alex, Adeola, me & Ona-ara, at our last day in the workshop in Bingham, Abuja.
Oda-aro in Yoruba means good night, but in my heart it means seen you soon. I miss the warm friends I made there, I miss their uncontained joy, their spontaneity and generosity, their wise and serene takes on life (which actually brought me closer to religion), I miss the colourful attires in the street and the feeling like I time travelled to summer in February. I miss the hawks which flew around the UI campus and the hazy sky. I try to make it up with listening to Nigerian music almost every day and staying in touch.
When I told people around me I was going to Nigeria, a country where the travel security advice is quite grim, I was met with so much resistance and doubt – it cannot be overstated. You hear not only about petty crime or terrorism but also about regular kidnappings, and the advice not to travel by road or be out in the dark makes one realize security things we take for granted, at least I did in my quiet Heidelberg home. And yes, I was hesitant and apprehensive, but I trusted my guts and my values: I deeply believe that science is global and has to be shared. And I put my actions where my words were: I went. It was crucial for me that I had the support of DrosAfrica and that I trusted my host – who was incredible – and this is something you should take into account too. Everything went fine, but I lived a very controlled life: I never left campus or walked around after dark without company; for the outreach, we visited gated schools with security; our accommodation was chosen strategically; between Ibadan and Abuja, we took a plane instead of the road. Indeed, I heard of the precautions people take in their daily life in regards to which cabs they get into; I heard a testimony in a church service about a kidnapping that fortunately ended well. But the people I met live regular lives which didn’t seem to me to be overwhelmed by these issues. So although we had no issues, I also confirmed that indeed, the travel advice is based on threats that do exist. This for me presents an interesting paradox: if we haven’t been somewhere, we can only rely on the pictures the news gives us. But if you take precautions, that shouldn’t be a reason to stay home, because there is so much life behind the news, and even I speak humbly from a miniscule experience of 2 weeks. So much warmth, so much culture, so much diversity, news ways of living and thinking and looking at science and life and on and on…
If you read this and you are torn, please go. Prepare, take cautions, but go!
Nature in UI
This visit had the support of DrosAfrica, for which I am very grateful. In particular, thanks to Isa Palacios for always being there. ELLS and EMBL Comms supported the school visits – thanks Eva and Verena! I am grateful to my supervisor Justin Crocker for being supportive and to several colleagues (in and out EMBL) who shared material, insight, and especially those who shared encouragement.
A postdoctoral position is available for an initial period of 2 years at the “Stem Cell and Brain Research Institute” (www.sbri.fr) in the lab of Dr Olivier Raineteau.
The project follows two recent studies from the team demonstrating transcriptional heterogeneity of postnatal neural progenitors (Donega et al., Cell Report, 2018), and their amenability to pharmacological manipulation (Azim et al., Plos Biology, 2017). It aims at using transcriptomic, as well as fate-mapping approaches to study neural progenitors (endogenous or induced) and their capacity to produce define cell types, including distinct neuronal subtypes. The project involves close collaborations with the laboratories of Denis Jabaudon (CMU, Geneva) and Christophe Heinrich (within the SBRI institute).
We are seeking highly motivated candidates with a PhD in biological sciences with a strong interest in developmental neurosciences. The candidate will have an expertise in fate mapping approaches. Previous experience with bio-informatics analysis (e.g. single cell RNA-Sequencing analysis, R Studio, Seurat) is also required.
Environment: The team has a long-standing expertise in the field of postnatal forebrain neurogenesis and CNS repair. It is part of the Stem cell and Brain Research Institute (SBRI), and exciting international multidisciplinary research centre. The working languages are French and English.
Job information
Closing date: 15/06/2020
Employment start date: 01/09/2020
Institution: Inserm U1208
Department: Stem cell and Brain Research Institute
Contact Information
Dr Olivier Raineteau Stem Cell and Brain Research Institute
INSERM U1208
Applicants should send their CV, a motivation letter, 3 references (name, e-mail, address, phone no.) before the 15th of June to: olivier.raineteau@inserm.fr
Selected publications :
Donega V, Marcy G, Lo Giudice Q, Zweifel S, Angonin D, Fiorelli R, Abrous DN, Rival Gervier S, Koehl M, Jabaudon D, Raineteau O (2018) Transcriptional Dysregulation in Postnatal Glutamatergic Progenitors Contributes to Closure of the Cortical Neurogenic Period. Cell Rep. 22(10):2567-2574
Azim K, Angonin D, Marcy G, Pieropan F, Rivera A, Donega V, Cantu C, Williams G, Berninger B, Butt AM, Raineteau O (2017). Pharmacogenomic identification of small molecules for lineage specific manipulation of subventricular zone germinal activity. Plos Biology; 15(3):e2000698.
Azim K, Hurtado-Chong A, Fischer B, Kumar N, Zweifel S, Taylor V, Raineteau O (2015) Transcriptional Hallmarks of Heterogeneous Neural Stem Cell Niches of the Subventricular Zone. Stem Cells. 33(7):2232-42
Social media gets a hard time these days, and in some instances rightly so. For the scientific community however, it’s a powerful platform for informal science communication and fruitful collaborations. On Twitter for example, the developmental biology community shares news, discusses research, celebrates publications and commiserates grant rejections. It can be a supportive, informative and fun place that highlights life at and beyond the bench. With 13.9k and 15.8k followers respectively, Development and the Node use Twitter to interact with this community, promoting their content as well as engaging with authors and readers.
While Twitter is our go-to, it isn’t used everywhere and The Company of Biologists (the not-for-profit publisher of Development) has been focusing its efforts on audiences that can’t be reached through the Twittersphere. One such audience is in China, where different social media platforms are used, and manuscript submissions and readership figures have been steadily increasing. So, last summer we launched a Chinese WeChat channel.
Social media in China
WeChat was developed and released by Tencent in 2011 and has since become one the most popular social media applications in China. Want to search for news articles? Use WeChat. Talk to friends? Use WeChat. Order a takeaway? Use WeChat. Pay for a meal before you even arrive at the restaurant? Use WeChat. Figures from the end of 2019 indicate that WeChat’s monthly users have increased to a whopping one billion.
(L) The Company of Biologists’ WeChat feed; (R) The first post on the account included introductions from the company’s Board of Directors.
Science on WeChat
Much like on Twitter, a lot of scientific discussion happens on WeChat, and many Western scientific organisations already have WeChat channels to promote their work. Since the launch of our WeChat channel, we’ve accumulated a following edging towards 600 and this number is continually growing. Given our relatively low profile and lack of a physical presence in China, we’re pleased with this growth and are excited to build a community of engaged Chinese researchers.
We publish articles on the channel once a week that highlight some of the many thing The Company of Biologists does, be it the latest research, interviews, posts from the Node, Company announcements, grant information, Workshops, Meetings – there’s a lot to share. We’re also running a series providing advice to support Chinese authors in their publishing experience with us. Subjects in this series covered so far include a video about how to frame a research question, the process of submitting to all five of The Company of Biologists’ journals and top tips on promoting research after publication.
Screenshots from three articles published on WeChat: (L) an interview with a preLighter; (middle) a Q&A with first authors; (R) tips on how to promote research.
We’re fortunate to work with a supportive agency who assist us with the translations of our articles. Once the articles are published in local time, users can share content that they find interesting in WeChat groups or tap the ‘Wow’ button to promote the article in their own networks.
The future
Our main aim this year is to establish a working group of Chinese early-career researchers. We’d invite members of this group to work on the channel with us, which could be in the form of guest posts, checking the translations of our content, or providing insights into relevant topics. If you or anyone you know would be interested, please do get in touch – simply email wechat@biologists.com.
The Bloomekatz laboratory in the Department of Biology at the University of Mississippi in Oxford, MS is seeking a research technicianto assist in our investigations of cardiac morphogenesis and disease using zebrafish. We utilize an innovative combination of genetic, live-imaging, biophysical and system-biology approaches to elucidate the mechanisms underlying morphogenetic and identity transformations in the heart. Please see our website https://thebloomekatzlaboratory.org for details on our research. The successful candidate will have the opportunity to be involved in all aspects of the research and publication process, from experimental design to data analysis and publication. Duties may involve – conducting developmental/cell biological experiments, zebrafish husbandry, analyzing imaging and large datasets.The candidate will work closely with and be trained by Dr. Bloomekatz
Interested in joining our dynamic group apply online: https://careers.olemiss.edu, search zebrafish. Please submit a cover letter and resume. Salary dependent on experience. This position is eligible for benefits. Anticipated start date Summer or Fall 2020. This is a yearly position, which may renew dependent on funding.
-Further questions can be directed to Dr. Bloomekatz at josh@olemiss.edu. The University of Mississippi is an EOE/AA/Minorities/Females/Vet/Disability/Sexual Orientation/Gender Identity/Title VI/Title VII/Title IX/ADA/ADEA employer.
The Node is a community site for developmental biologists, and is driven by content written by the community – once registered, you are free to post without requiring authorisation or approval. Today I want to share some ideas for how you could contribute to the Node, during the current COVID-19 pandemic and beyond (I recently circulated these ideas in our ‘Occasional Writing Ideas’ newsletter, which you can sign up for if you register for a Node account). Blogging might be the last thing on your mind at the moment, but the chance to write and connect with other researchers across the world could provide some welcome respite.
Here are some ideas for ways you can contribute to the Node:
Tales from isolation
How are you coping being away from the lab? Do you have any tips for other researchers? This could relate to science (e.g. online training resources) or personal wellbeing/mental health.
We would love to hear voices from across the world – pandemic diaries from Delhi to Delaware.
If you prefer speaking to writing, another option is a series of short video interviews with scientists in lock-down. Get in touch if you’d like to be involved.
Virtual meetings/symposia/seminar series
Organisers – which technologies and formats worked, which didn’t?
Attendees – how did it compare to being there in person? Is this the future of scientific conferencing?
Have you been part of one (as examiner or examinee)? What was the experience like? Any tips for those preparing for one?
Lablife
Which aspects of lab life have/haven’t you been able to replicate online?
Remote lab meetings – dos and don’ts.
PIs – any tips for maintaining lab spirit remotely?
Model organisms – how are they coping without you, and how are you coping without them?
Behind the paper stories
Have you recently published a paper or preprint? Tell us the story behind it – this could feature the personal side of scientific research or go deeper into the technical details than a paper allows
Catching up with the literature
Write a ‘Research Highlight’ on a paper that recently blew you away. A good chance to try out less formal scientific writing, and help promote the science you love.
Our Forgotten Classics series explored unjustly overlooked papers in the history of developmental biology – we’d love to hear about your Forgotten Classic.
Resources
Our Resources page contains content on advocacy, outreach, education, audiovisuals and research – have we missed anything useful, particularly for researchers at home? Get in touch.
Networking
If you’re missing out on networking in person, why not use and join the Node Network, our global directory of developmental biology and stem cell researchers. It’s designed to help those organising conferences, looking for referees and so on to identify individuals who might not otherwise come to mind. Maybe you’ll find your future collaborators there.
If you’re interested in writing anything for the Node, I’m happy to help at any point of the process, from sketching out an outline to editing drafts to helping with the final posting of the piece. I’d also love to hear ideas for different kinds of content not explored above – just email thenode@biologists.com.
Our lab investigates the role of hydrostatic pressure as a morphogenetic force using zebrafish as a model system. This work was originally focused on tube formation and had revealed a crucial role for fluid secretion in single lumen formation (Navis and Bagnat, 2015). When I joined, the lab was conducting a forward genetic screen looking for phenotypes involving fluid regulation. We found many mutants with defects in the anterior-posterior (AP) axis and this brought our attention to the notochord. The notochord is the central structural element in the AP axis of all chordates and in vertebrates it serves as scaffold for the spine. In the developing vertebrate embryo, the notochord acts as a hydrostatic skeleton (Adams et al., 1990) and is important in the patterning of several tissues including the somites, blood vessels and pancreas. While the exact morphology of the notochord can differ between species, one key feature is highly conserved: the presence of large, fluid-filled vacuolated cells, also known as chordocytes (Grotmol et al., 2003). These cells are found in all vertebrate embryos and they persist beyond early development, being found in the nucleus pulposus of the intervertebral disks in mice, pigs, and humans (Lawson and Harfe, 2015). Their most salient feature is that the vast majority of their cell volume is occupied by a giant (~40µm) fluid-filled vacuole (Fig 1).
Fig 1. DIC and fluorescent image of a dissociated vacuolated cell from a 3 dpf zebrafish embryo. The cytoplasm is labeled with GFP surrounding a large central vacuole. Scale bar=50 µm
The zebrafish notochord is comprised of three parts: a core of large vacuolated cells; a layer of epithelial-like sheath cells that surrounds the core; and a thick extracellular matrix encasing the sheath cells. (Ellis et al., 2013b) (Fig 2.). When we started working on the notochord, we first wanted to define the identity of its unusual vacuoles. Combining a genetic and cell biological approach, we showed that notochord vacuoles are indeed lysosome related organelles which form via post-golgi biosynthetic trafficking and that they are crucial for embryonic axis elongation (Ellis et al., 2013a). Surprisingly, we also found that when vacuoles are disrupted during early development spine formation is also affected, causing a phenotype reminiscent of scoliosis in humans (Ellis et al., 2013a). Scoliosis is the most common developmental disorder of the spine and results in kinks and curvatures of the spines axis. Seeing spine malformations was a very exciting result for us and led us down a new road to understand how the notochord functions during spine morphogenesis.
Fig 2. Fluorescent maximum intensity projection of a live 5 dpf zebrafish notochord. Notochord sheath cells (green) are surrounded by vacuolated cells (magenta). Scale bar=100µm
To tackle this question, I started with a live imaging approach. We spent a lot of time generating transgenic lines to visualize the different cell types of the notochord and spine and learning how to image fish during late larval stages. While imaging the early embryo with confocal microscopy is relatively easy, imaging the notochord during spine development proved to be much more difficult. The tissue is thicker, external pigment develops, and it is much harder to keep the fish alive while on the scope. However, after a lot of trial and error we developed an imaging protocol that allowed us to image spine formation until about 6 weeks post fertilization. We also developed quantitative methods to determine the exact shape and position of every vacuolated cell in the notochord (Norman et al., 2018).
It soon became clear that vacuolated cells and their vacuoles persist through spine morphogenesis. Interestingly, we found that the morphology and arrangement of vacuolated cells changes during development. Vacuolated cells that remain under the growing vertebra change in shape from a rounded morphology to an elongated, pancake-like morphology; whereas vacuolated cells that end up in IVD (intervertebral disk) areas become tightly packed and their vacuoles fragment (Bagwell et al., 2020). It appeared as though the vacuolated cells are squished under the concentrically growing vertebrae, but are more rounded and clumped together in the IVD domains. This led us to hypothesize that the vacuoles are important in providing a scaffold that is able to initially resist the pressure of the growing vertebrae, symmetrically and consistently, allowing for the development of a straight spine (Fig. 3 A,C,E).
Fig 3. (A-B) Live confocal images of the zebrafish notochord prior to bone formation in WT (left) and spzl-/- (right). The cytoplasm of the vacuolated cells are labeled with SAG:gal4;UAS:GFP. Vacuoles are marked with an asterisk. (C-D) Live confocal image of the zebrafish notochord and spine at juvenile stages. The cytoplasm of the vacuolated cells is labeled with SAG:gal4;UAS:GFP and osteoblasts are labeled with osx:mcherry-NTR. Asterisks mark inflated vacuoles. Arrows indicate areas of spine kinks. Scale bars for A-D =100 µm. (E-F) Micro-CT heat map depicting relative bone density for 6 wpf WT (left) and spzl-/- (right). Arrows indicate spine kinks. Scale bar=1mm
At this point in the project, we were incredibly fortunate to collaborate with Didier Stanier, whose lab had carried out a forward genetic screen to identify mutants with defects in endodermal organs. They had found, by chance, a viable mutant with a shortened embryonic axis and what appeared to be a severe scoliosis phenotype. Because Didier knew we were working on understanding spine morphogenesis and the origins of scoliosis, he sent the mutant to our lab. This little mutant was so twisted and short, we affectionately named it spaetzle (spzl) after the German pasta (incidentally, Didier’s lab moved to Germany shortly after that). Right away we saw that the vacuoles in spzl were smaller and fragmented, and live imaging revealed that the vacuoles continued to deteriorate throughout development, leaving intact cells with really small or no vacuoles at all. We were surprised to find that the notochord and the AP axis were initially straight in spzl mutants. However, as vertebra formed the notochord was unevenly deformed, and severe kinking ensued as the bone grew (Bagwell et al., 2020). It was then clear that this mutant was a great genetic model to investigate the role of notochord vacuoles in spine formation.
The first step for experimentally testing our ideas was to locally disrupt vacuoles to see if spine curvatures or kinks would occur at those specific locations. Simple right? There are many tools ablate cells including nitroreductase lines, photo ablation and physical injury, just to name a few. We had nitroreductase transgene perfect for this experiment and we could express it mosaically, kill a few cells and then see what happens with the spine. So I tried it successfully killing the cells, raised them to juvenile stages, and imaged their spines, but found no scoliosis. I was puzzled: how could we have such a strong phenotype in our spzl mutant, but be unable to reproduce the phenotype experimentally? Around this time Jamie Garcia, a graduate student, joined the lab and “Team Notochord”. She was looking at the role of cup shaped invaginations called caveolae, which the Parton lab had shown to be incredibly abundant in the notochord (Nixon et al., 2007). In parallel studies, Jamie and I on one hand (Garcia et al., 2017), and the Parton lab on their own (Lim et al., 2017), showed that upon locomotion, vacuolated cells lacking caveolae collapse, causing lesions in the notochord. We then found that as the vacuoles burst they release their contents, particularly ATP and UTP, which induce notochord sheath cells to locally invade the notochord core, transdifferentiate, and vacuolate, thus restoring the integrity of the notochord and allowing for a straight spine (Garcia et al., 2017). This finally explained why mutants lacking caveolae did not have a spine phenotype and why all the ablation assays I tried and tried did not work.
This ability of the notochord to regenerate vacuolated cells upon physical or mechanical injury reinvigorated our hypothesis that vacuolated cells are critical for spine development. I thought that if the notochord has the ability to fix itself, it must be important for later development. While vacuoles are lost in the spzl mutant, vacuolated cells remain intact and do not induce any sheath cell invasion or vacuolated cell regeneration. Through light sheet microscopy, I showed that spzl mutants are unable to undergo vesicle fusion to the vacuole membrane and are therefore unable to make and maintain a fully inflated vacuole, leaving a notochord that is lacking an even distribution of fully inflated vacuoles. Using nuclear deformation assay that James Norman and I developed, we also found that loss of vacuole integrity reduces the internal pressure of the notochord. Then, as vertebrae begin growing and squeezing the notochord, the structure deforms irregularly and is unable to absorb compression evenly. As a result, asymmetric deformations develop along the notochord, ultimately leading to severe kinking of the spine axis (Bagwell et al., 2020) (Fig 3 B,D,F). We were also able to recapitulate the mechanism with an experimental manipulation by expressing a dominant-negative form of the GTPase Rab32a. We showed that mosaic expression of DN-GFPRab32a causes vacuole fragmentation and local spine deformation at juvenile stages, further confirming our hypothesis. With the help of Sarah McMenamin’s lab we were also able to show using high-resolution micro CT imaging that loss of notochord vacuoles also leads to increased vertebral bone mineralization, suggesting notochord stiffness and vertebral bone formation are cross-regulated (Bagwell et al., 2020).
Our notochord journey started about 10 years ago. Our path began by asking two simple questions: what are notochord vacuoles and what are they good for? Like many questions in science this has led us down a road with lots of forks, turns and roadblocks. The forks in our path have led us to many new and exciting stories about the notochord such as its role in spine segmentation (Wopat et al., 2018), and there are many more to come. We have learned so much about this simple yet dynamic structure, but what is clear is that there is still so much more to learn. In the words of Yogi Berra
There is an open PhD position available in my lab. The project deals with the role of glial cells in post-ingestive nutrient sensing in Drosophila. Please see the advertisement for further information: Stellenausschreibung_Schirmeier.
Research into genetic conditions relies on information from patients and their families, whether that’s detailed health records or genomic data. As the tools and techniques for DNA and data analysis become cheaper and more organisations get in on this fast-growing field, it’s vital to make sure that the most valuable research resource – human lives – doesn’t get overlooked in the rush.
Fiona Copeland is the chair of a support group for UK families affected by primary ciliary dyskinesia or PCD – a rare genetic condition affecting the lungs – and is the mother of two adult sons with the condition. She explains what her role as a patient representative involves and shares her advice for how researchers can engage and involve patient groups more effectively. Her top tip? Don’t make children cry!
We also chat to Patrick Short,CEO of Sano Genetics – a Cambridge-based startup that aims to connect researchers with patients who want to take part in genomic research.
Finally, we hear from Shelley Simmonds, a disability rights campaigner and rare disease advocate whose son Fraser was initially given a diagnosis of Duchenne Muscular Dystrophy as a baby. When Fraser didn’t seem to be progressing as might be expected for a child with the disease, she and her family got involved in Genomics England’s 100,000 Genomes Project in search of clarity – but things turned out not to be quite so simple. Shelley talks what happens when the question “What’s wrong with my child?” has no answer.
If you enjoy the show, please do rate and review on Apple podcasts and help to spread the word on social media. And you can always send feedback and suggestions for future episodes and guests to podcast@geneticsunzipped.com Follow us on Twitter – @geneticsunzip
Last week, I gave a talk (online, of course) about ‘Writing review articles’. It was aimed at graduate students who, as part of their training, had to identify a topic in the field of developmental biology and write a mini-review on that particular topic. However, my talk contained some general advice about writing review-type articles, as well as some general writing tips, so I thought I’d share a summary of it here.
Types of Review articles
I guess the first thing to point out is that review-type articles come in lots of different ‘flavours’. They all vary with regard to length, scope, style and overall purpose, and are given different names by different journals. But they all aim to summarise and distill research findings. This makes them very different to primary research articles, which aim to present data, although they are handled in similar way, i.e. they are submitted to a journal and peer-reviewed by 2-3 experts in the field.
The many names that journals use to label review-based articles
What’s the purpose of a (good) Review article?
A good review article might aim to:
summarise key research findings
highlight ‘must-read’ articles in the field
act as educational material
However, an excellent review article will also:
be timely
provide critique of studies
highlight areas of agreement as well as controversies and debates
point out gaps in knowledge and unanswered questions
highlight current technologies that are helping/can help the field
suggest directions for future research
But remember that readers are usually a mix of experts and non-experts who will be looking for very different things so a good review will cater for both of these audiences. For example, a graduate student might turn to a review article when they start in a new lab to find out more about the history of a field, or to get a summary of key findings. By contrast, an experienced post-doc or PI might want to read a review written by one of their peers to find out what the current state of thinking in a field is. Ideally, a good review should therefore aim to provide a combination of balanced summaries and critique whilst being authoritative, forward-looking and inspirational. However, note that the exact ‘flavour’ or format of the review will also dictate its purpose, e.g. a ‘Perspective’ article in Journal X might aim to summarise a handful of recent studies, whereas an ‘Essay’ in Journal Y might aim to provide a more comprehensive analysis of the last decade of research.
The things that different types of readers look for in review articles
Where to begin?
The first step is to choose the topic you want to write on and come up with a rough idea of the scope of your article. You may already have this in mind but it’s important, before you begin writing, to really nail the exact purpose of your article. To help you do this, I‘d suggest the following:
Identify the particular theme/topic/idea that you want to focus on. In most cases, this will be something that’s closely related to the topic you work on, e.g. you might be working on something, or reading up on a particular area, and feel that a review would be helpful. If you need inspiration (i.e. if you want to write but aren’t sure what to write about), read, speak to people, and think about talks you’ve been to. What’s exciting in your field right now? Are there papers that change the way we think about something? Have you seen/read papers that converge on a similar theme/idea?
Check that there aren’t already reviews on this topic, i.e. something that’s been published within the past year or so. This is important; no-one wants to read a review that doesn’t offer anything new.
Decide if there is enough recent material to include (or too much). At this point, you may need to go back to the drawing board to either expand on or refine the scope of your article. It’s also helpful to read a few reviews (mini-reviews vs longer reviews) to get a feel for how much material a review can cover.
Identify and write down the main aim/purpose of your article. What’s the key message you want to get across? Why is this important and timely? Why would people want to read your article?
Note that lots of reviews are commissioned, i.e. the author is invited to write by a journal/editor. So, if you know you want to write a review on a particular topic and have a pretty clear idea of what your review will cover, a good place to start is by contacting a journal to see if they’d consider it. This also then means that you’ll (hopefully) be working alongside an editor from the outset to develop and refine the scope of your article. You’ll also have your target audience, article format and word limit in mind while you’re writing so can tailor the review accordingly.
Before you begin writing
Plan, plan and plan some more! Having worked with authors on review-type articles for years now, I can’t stress this enough.
Think about the sections/sub-sections you might use. What material would you cover in each of these? What’s the message of each section? How can you link the sections?
Think about the key concepts/words/specialist terms that you need to introduce and define. Where, when and how should you introduce these? (e.g. in Intro, in a figure, in a text box). What needs to be introduced first? What’s the best order in which to discuss these?
Think about the display items (figures, text boxes, tables) that might be helpful. How/when should they be used? What material would they contain?
When you start writing
Once you have a plan, you can start writing. I’d suggest that you start with the Title, Abstract and Introduction – these are the first parts that the reader sees of the article so they need careful thought. By starting off with these, you’ll also have the scope/purpose of the article clear in your own mind. You can then work on the main text of the article (the ‘meaty’ bit) and the Conclusions with this scope/purpose in mind, although you’ll need to return to the Title, Abstract and Introduction for a tidy up once you’ve written the main text.
Things to think about:
Title, Abstract and Introduction: These should be short and self-contained, and should complement each other. Each one in turn should provide more detail, aiming to draw the reader in. Remember: lots of readers will only read the title and abstract (e.g. when they search for articles in Pubmed) so these basically act as a ‘hook’ to grab their attention. They also need to be ‘discoverable’ on the Web, i.e. database friendly and containing the relevant keywords.
Choosing a title: Choose something that is short, clear and self-explanatory; try to avoid puns/idioms and colloquial phrases or references. Try to convey the key message but also provide context.
Abstract: The abstract should then aim to highlight the most important parts of the article. The answers to the following 5 questions provide a good starting point: What is the main topic you’re going to focus on? What do we know so far? What is new/why is this now an interesting time for this field? What are the broad implications of these newer findings? What does your review aim to do?
Introduction: The Introduction should then expand on the Abstract and set the scene. Provide context by first introducing the topic: why is this topic interesting/significant, what do we know about it so far, how has the field progressed, what has the new progress shown? Ideally, the Introduction should end with a clear description of the article’s scope, aims and structure, i.e. a walk-through of the main topics that will be discussed and the order in which these will be covered. This just lets the reader know what they can expect from the article. If possible, introduce or re-iterate the main ‘message’ of the article.
Conclusions: Emphasize the key message or theme of the article and, if needed, reiterate the data that support this message. Highlight the broader significance of this conclusion. Finally, if possible, bring your voice to the article: What do you think are the most compelling questions raised by these studies? What approach(es) could be taken to address these open questions? Are there technical hurdles that need to be overcome? What are the broader implications of this, i.e. why are further studies needed and what benefits might they offer?
Display items: Use figures to emphasize or illustrate key concepts/processes, or to introduce or summarize. Remember that figures should ideally act as stand-alone items; you should be able to follow them by eye and without referring to the main text, although each figure should have a clear title and a figure legend the walks the reader through the figure. In general, schematics are easier to follow than images reproduced from primary articles. Tables can be useful for summarizing lots of information, for comparing/contrasting things, or for highlighting advantages and disadvantages. Some journals encourage the use of text boxes, which can house additional or background information or material that is peripheral to the main theme of the text.
General things to think about while you’re writing (and to re-visit before you finish off!)
Structure
Try to group your discussion into sections/sub-sections. This just helps to break up long chunks of text (and helps to keep the reader interested). If you already have a plan (e.g. a list of headings/sub-headings) this structuring will be much easier.
Each section should begin with a small introduction.
Each sub-section (and/or even each paragraph) should then have a clear message/point to it, e.g. What question did particular sets/types of studies set out to address? What did these show (and here you can go into the detail)? What could be concluded from these?
It’s also helpful to add in a few lines to wrap up each section and ease transition into the next section.
Content
Make sure that all statements are adequately supported by a citation. Cite the source/primary article whenever possible (but note that it is okay to cite Reviews for established concepts or to refer to a large body of evidence).
Think about the word count and how much can be covered/how much detail you can go in to; you may find that it’s easier to write lots first then trim at a later stage.
Avoid regurgitating the conclusions drawn in the papers you cite without giving them some thought.
Don’t shy away from discussing findings that contradict each other. It’s better to highlight what can/cannot be reconciled and the possible cause of any discrepancies. Also use this as an opportunity to draw out the questions that remain and discuss how these questions could be addressed.
Similarly, remain balanced – make sure you discuss the findings from the field as a whole (and not just the data from a few select labs).
Make it clear when you are stating results versus providing speculation or alternative interpretations.
Provide critique if you can…but keep it polite and constructive.
Accessibility
Remember your audience: the article needs to accessible to expert and non-expert readers alike.
Introduce/define/explain specialist terms, cell types, tissues, phrases on first mention.
Consider using display items to house any material that a non-expert reader might find useful.
Don’t assume the reader knows what you’re thinking and how things link together; you might feel like you’re sometimes stating the obvious but it’s better to do this than to leave readers feeling lost.
Style
Stick to using clear and simple sentences…but try to vary the pace of your writing, e.g. by using a mixture of long and short sentences.
A general rule is to write as you would speak, using active rather than passive tense/sentence construction.
Be thrifty with your words: completely eliminate any that aren’t needed.
Avoid vague sentences. For example, say ‘Factor A causes an increase/decrease in Factor B’, rather than ‘Factor A modulates Factor B’.
Importantly, be patient and don’t get frustrated! A good writing style needs to be developed over time and comes with practice. Of all the things highlighted above (structure, content, accessibility and style), I’d say that style is the hardest to really nail. Getting a good and consistent writing style is also challenging if you have multiple authors working on the same article. In this case, I’d recommend that you nominate one author to do a final comb-through to iron out any inconsistencies, although hopefully you’ll have an editor who’ll also assist with this! On this note, I should point out that the amount of input you receive from an editor will vary from journal to journal, e.g. some journals have dedicated editors who spend a significant amount of time, working alongside the authors, to edit and improve a review.
Developing your writing style
Finally, some tips from fellow editors!
We have a bunch of experienced editors here at the Company of Biologists so I asked them all for their key pieces of advice. Here are just some of the things they suggested:
Plan, plan, plan – make sure you have a good idea of the overall structure before you think about details
Get feedback. Before you submit your review, send it to someone whose opinion you trust and ask them for their honest thoughts. Don’t be discouraged if they give lots of feedback – this is exactly what you want!
A review shouldn’t just be a list of facts, e.g. X showed this, Y showed this, Z showed this. A narrative thread or argument that connects is much more engaging.
Take time to pull back and look at the overall structure. Does it make sense? Can you see how the ideas join together and flow from beginning to end?
Remember that readers aren’t psychic. Explain why you’ve chosen the scope you have, why you’ve chosen to discuss particular examples, why you’re moving on to the next topic. Also make sure you clearly link up relevant observations and state conclusions rather than expecting the reader to make connections.
Don’t assume that the reader can link two statements that you might be able to link in your mind; you have to explain the link.
Think about the graphics at an early stage – figures can often feel like a bit of an afterthought but good figures can really help to get the message across far more concisely than text.
Break the article up into sections so that people can easily find the particular piece of information they might be looking for; recognize that not everyone is going to read from start to finish.
Remember that your readers will know far less about the topic than you do. So before you dive into the new and exciting findings in the field, make sure you’ve given a clear overview of the system you’re writing about. Imagine that you’re writing for a new PhD student who’s never worked in this particular field.
One final point: there’s no ‘winning formula’. This is just my advice based on the articles I’ve handled and the authors I’ve dealt with, so you may find that some of it doesn’t work for you or that someone else’s advice differs. Ultimately, you should aim to develop a writing approach, technique and style that works for you.
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