In the recent BSDB-the Node virtual art exhibition, Christoph Markus Haefelfinger’s ‘The backbone of stem cell derived embryos’ was selected as the Judges’ Choice runner-up in the ‘Scientific images’ category. We briefly caught up with Christoph to find out more about his research and the story behind the image.

What is your background?
I am a final year medical Student from Switzerland, currently applying for a PhD in developmental and stem cell biology in the UK. At the time I took my confocal image, I was a Summer Undergraduate Research Fellow in the laboratory of Professor Magdalena Żernicka-Goetz at the California Institute of Technology.

What are you currently researching on?
I am continuing my work at the Żernicka-Goetz lab at the University of Cambridge in parallel to clinical placements at the Universities of Cambridge and Oxford, researching preimplantation development using a mouse stem cell derived embryo model. More precisely, I aim to help solidify the scientific confidence in utilising bioengineered embryo models to study specific developmental questions.

Can you tell us more about the story behind your image ‘The backbone of stem cell derived embryos’? 
To me, the image signifies the culmination of my ten week fellowship at Caltech learning the ins and outs of stem cell derived embryos, and is one of my proudest achievements. I had a truly wonderful and eye-opening experience grounded in cutting-edge research and exploring the Western USA with amazing friends and colleagues, and many of these emotions are strongly tied to my picture. I am therefore even more proud and grateful for the amazing feedback by the jury and the public – it is truly a fantastic feeling to have so many of you appreciate my image which is so close to my heart!

What is your favourite technique?
Choosing from the techniques I had the chance to learn and apply myself as an undergraduate researcher, I must go for live imaging using fluorescent reporters. I believe there are few techniques that hold the promise to not only provide quantifiable data, but to spatiotemporally visualize highly complex processes in an unparalleled beauty. Especially in the context of developmental biology, I know of no other method that could capture the dance of life in a more mesmerizing way, making it an easy choice for me.

What excites you the most in the field of developmental and stem cell biology?
I am captivated by the fact that we all originate from a single cell. To me it sometimes still is an abstract thought, and seeing an embryo develop – human, mouse, or stem cell derived – excites me every time. This enthusiasm translates into my strong curiosity for cell fate acquisition, and how it interrelates with self-organisation, spatiotemporal crosstalk, and its regulatory foundation on an omics level. I am therefore truly excited to continue researching development in my PhD.

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In this SciArt profile, we get to know more about Morag Lewis, the scientist behind the artwork ‘Castle of Dreaming Dragons’, which was chosen as the Judges’ choice runner-up in the Node-BSDB virtual art exhibition.

Can you tell us about your background and what you work on now?

I’m from the UK, and I study the genetics of progressive hearing loss in the lab of Professor Karen Steel at King’s College London. The project I have been working on most recently involved analysing sequence data from several large human cohorts and developing different methods to identify genes and variants which might be contributing to the different types of hearing loss observed in the participants.

Were you always going to be a scientist?

I remember not knowing what I wanted to do when I grew up, but I studied the subjects I enjoyed most and I’m pretty happy with where I ended up. I did take a side trip through computer science between my undergraduate degree and my PhD, which turned out to be very useful further down the line.

And what about art – have you always enjoyed it?

I have always enjoyed doodling, to the point where I used to worry about being given a new rough book at school – the teachers always checked to make sure the old one had been used properly and I didn’t think covering the pages with horse doodles counted! And I have always told stories, but usually just to myself.

What or who are your most important artistic influences?

I would say the most important artistic influences on me are writers such as Lois McMaster Bujold and Martha Wells, and artists like Kaoru Mori and Hitoshi Ashinano, but they are the tip of the iceberg. If I read something I like, it’s hard not to be influenced by it.

How do you make your art?

I mostly make comics, and I use coloured pencils to draw, then I ink over the pencils with a dip pen, brush, and ink. For colour work, I use watercolour paints and alcohol markers. But in both cases, I scan and edit the results digitally.

Does your art influence your science at all, or are they separate worlds?

I don’t think my art and science influence each other directly, but I find keeping a good balance between them means I can do both better, if that makes sense. When it comes to preparing figures for papers, or posters for conferences, my experience with making and printing comics is invaluable.

What are you thinking of working on next?

I actually started out wanting to write books rather than comics, because I was a novel reader as a child rather than a comic reader (that came later). I have recently been experimenting with prose again, and have produced an illustrated novel. I’d like to keep doing that, and I have an idea I very much want to develop… when I get some of my existing projects finished!

Find out more about Morag:

Website: toothycat.net

Instagram: @toothycat

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I read the name of Pere Alberch for the first time while leafing through a collection of articles on Ecology and Evolution edited by the Universidad Autónoma de México [1]. At the time I was a bachelor’s student of Biology at the University of Turin, desperately collecting material for my final dissertation on the role of physical parameters in shaping form during embryo development. In the paper “Evolution and complexity: developmental constrains” by B. Luque & J. Bascompte, I found out that Pere was a “blighted theoretician of development and experimental embryologist” who did seminal work on the development and evolution of the tetrapod limb. Despite having only recently closed my textbooks of Developmental and Evolutionary Biology, I had no idea that Pere was one of the founding fathers of Evo-Devo, a field that aims to connect evolutionary novelty to developmental dynamics, i.e. “phylogeny” to “ontogeny” [2]. To my surprise, most of his work was indeed rarely cited and his name would have been certainly forgotten were it not for the visionary power of his ideas and the determination of his scientific disciples, who so tenaciously kept those ideas alive.

Almost ten years later, I have had the chance to follow a celebrative symposium on Pere’s work, set in Barcelona, just few kilometres from where he was born. “Genes, cells and embryos in development and evolution: Pere Alberch 25 years on” took place at Barcelona Biomedical Research Park (PRBB), on the 9^th and 10^th November 2023, organised by Alfonso Martinez-Arias (Universitat Pompeu Fabra), Denis Duboule (École Polytechnique Fédérale de Lausanne) and James Sharpe (EMBL Barcelona). As the title suggests, the symposium aimed to cover each of the biological scales which are relevant to the study of development and evolution of form (the genetic, cellular and tissue scale), whose tight integration at the embryo level had been so consistently emphasized by Pere. Here is the link to the event:  https://eventum.upf.edu/94510/detail/genes-cells-and-embryos-in-development-and-evolution-pere-alberch-25-years-on.html.

Who other than Denis Duboule could kick off the first session, entitled “Constraints and the hourglass”? His talk highlighted how the range of morphologies in the early stages of vertebrate embryonic development, during the so-called “phylotypic stage”, is restricted already at the chromatin level, with the Hox timer being one of the main agents constraining the ‘neck’ of the hourglass model. The presence of phenotypic invariance, of which the “phylotypic stage” is an example, was what intrigued Pere the most, together with the study of abnormal phenotypes or “monsters” as a powerful tool to get a glimpse into otherwise hidden developmental rules [3]. The next speaker, Freiton Gallis (Leiden Biodiversity Center), built her research upon these two aspects, focusing on the conservation of the number of cervical vertebrae in mammals and on the analysis of vertebral defects such as cervical ribs. Arkhat Abzhanov (Imperial College London) illustrated his work on cranial shape variation in amniotes, followed by Michael Richardson (Leiden University) who fascinated the audience with a story of coevolution between a parasitic fish and the mussels that host its peculiarly-shaped eggs.

Patrick Lemaire (Centre de Recherche en Biologie Cellulaire de Montpellier) used the “parameter space” proposed by Pere in 1991 [4] to guide us through the world of ascidian embryos which display an incredible invariance in morphologies despite the extreme genetic divergence among species and their phenotypic diversity as adults. Margarita Cardoso Moreira (The Francis Crick Institute), whose recently established lab explores the evolution of sexual dimorphism, highlighted how sex differences can be traced down even to the cellular level! Her talk was followed by Camille Berthelot (Institut Pasteur), whose lab exploits organoid models of the uterine epithelium to study a trait that, similarly to sex differences, evolves quite rapidly: embryo implantation. The session, entitled “Of genes and cells”, was finally closed by the provocative talk of Iñaki Ruiz-Trillo (Universitat Pompeu Fabra) who clearly stated that we are still quite far from understanding what the unicellular ancestor of animals, the source of all the phenotypic diversity we witness at the present day, looked like. We left for lunch with a glimpse of hope that, through the use of metagenomics and the sampling of new taxa of unicellular organisms, we will be able to better address the origins of multicellularity.

The afternoon session was a journey in Pere’s life, fortune and friends. It started with the talk of Gerd Müller (University of Vienna), one of Pere’s closest collaborators. His presentation showcased some of his old work with Pere on the archosaur limb [5] together with some more recent work on polydactyly, and was interspersed with pictures of their fruitful meetings and forays. While the philosopher Laura Nuño de la Rosa (Universidad Complutense de Madrid) explained the reasons why Pere may have been forgotten by the scientific community over the years, despite his relevance for the Evo-Devo field, Diego Rasskin-Gutman (Universitat de València) clearly expressed why he cannot forget his mentor and how Pere’s ideas deeply influenced the work of his own lab, including the development of the Anatomical Network Analysis (AnNA) for topological analysis of organismal form. In the last years of his life, before his premature death in 1998, Pere became director of the Natural History Museum of Madrid. Rafael Zardoya, the current director of the museum, gave the last talk of the session, showing the crucial role that Pere played in restoring the Museum to its former glory and how deeply his decisions are still impacting the organization of the museum today.

Day 1 of the conference closed with a keynote lecture from Neil Shubin, who was one of Pere’s first PhD students at Harvard University. His engaging talk gripped the minds of the audience, who very much enjoyed the narration of the discovery of the Tiktaalik fossil, the first fish venturing onto land. He mostly focused on his work on fin-to-limb transition in vertebrates and hinted to some new work he is envisioning to do on salamander limbs, which relates to his PhD project in Pere’s lab.

Ricard Solé (Universitat Pompeu Fabra) kicked off Day 2 of the conference, arguing that the logic of life is predictable since life itself has its own constraints: in order for life to exist, even in another planet, certain conditions need to be met. We came back to earth for the rest of the session, in particular to life in the waters: Berta Verd (University of Oxford), Joost Woltering (University of Konstanz) and Emilia Santos (University of Cambridge) each illustrated their research on teleost fishes. Verd and Santos both exploit cichlid fishes as model organisms to study the evolution of two different morphological traits: vertebral counts and pigmentation patterns, respectively. Interestingly, cichlid fishes display a wide phenotypic diversity despite bearing similar genetics, falling on the opposite side of the spectrum with respect to ascidians. Joost Woltering uses a variety of teleost fish models in his lab to look at morphogenesis and evolution of their dermal skeleton, with particular attention to fins. With James Sharpe’s talk we shifted from fins to limbs, having the chance of listening to some new insights on digit pattern formation, an intriguing follow-up to some of Pere’s old work [6].

The task to close the conference was given to another speaker that has been deeply influenced by Pere’s work: Cliff Tabin. He surprised everyone by announcing that his talk would focus on the physical forces shaping gut development, rather than the topic of heterochronic shifts in limb development. As an homage to Pere, he showed how the circular model of morphogenesis Pere proposed in 1989 [3] can elegantly explain the process of villification in chick gut tube, a topic that the Tabin lab has been working on for over 15 years. Pere stated that genes undoubtedly influenced cell properties and thus morphogenesis by contributing to tissue geometry, but that tissue geometry and so the morphogenetic outcome (the ‘structure’ itself), feeds back into gene regulation, making morphogenesis a rather dynamic process and, far less simplistic than what was previously thought. This was my favourite talk of the conference, since it unleashed the true revolutionary power of Pere’s ideas and their relevance in the study of development and evolution.

As Laura Nuño de la Rosa explained on Day 1 of the conference, there are a number of reasons for the aura of mystery around Pere’s work, which despite his relevance for the field of Developmental and Evolutionary Biology is very poorly cited. These include the fact that Pere had to close his lab in Harvard for lack of funding, his rather quarrelsome personality that did not make him popular among collaborators, and his premature death in 1998. By the end of the meeting, I understood more clearly why I had only encountered his name in a hidden collection of papers rather than in the textbooks or classes where I had first about Evo-Devo in University. As Alfonso Martinez-Arias stated in his closing remarks, this symposium proved that, despite “the slings and arrows of fortune”, ideas can outlive their creators and do not fade despite their work being ignored by the scientific community. The circular view of causation in morphogenesis, development as a new level of selection between genotype and phenotype, the genotype-phenotype maps, the importance of ‘monsters’: all of this we owe to Pere and we can only thank him for promoting avenues of research that are so relevant today.

References to Pere’s work:

[1] Benítez M. et al., ‘Frontiers in Ecology, Evolution and Complexity’, Copit-arXives, Mexico DF 2014.
[2] Alberch et al., ‘Size and shape in ontogeny and phylogeny’, Paleobiology, 1979, 5(3):296-317.
[3] Alberch P., ‘The logic of monsters: evidence for internal constraint in development and evolution’, Geobios, 1989, 12:21–57.
[4] Alberch P, ‘From genes to phenotype: Dynamical systems and evolvability’, Genetica, 1991, 84: 5–11.
[5] Müller G. and Alberch P., ‘Ontogeny of the limb skeleton in Alligator mississippiensis. Developmental invariance and change in the evolution of archosaur limbs’, Journal of Morphology, 1990, 203: 151–164.
[6] Alberch P. et al, ‘Size dependence during the development of the amphibian foot: Colchicine-induced digital loss and reduction’, Journal of Embryology and Experimental Morphology, 1983, 76: 177–197.

(2 votes)

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In my previous article, I discussed the importance of joining communities and finding your crowd. Following my own advice, I have joined the Japan SciComm Forum, the community for English-speaking science communicators in Japan. It is a warm and welcoming community with professional and aspiring science communicators. The community meetings happen once every two months with two speakers (one from Japan and one from abroad) presenting on a wide variety of topics. Some of the ones I attended included how to make science accessible for people of all abilities and the place of AI in science communication. If you are a science communicator from Japan, professional, or just interested in communicating your research, you can join here.

Japan SciComm Forum Conference: overview

One of the events I was looking forward to during this year was the Japan SciComm Forum Conference. You can check out the schedule and speakers here. By the way, you can find YouTube videos from past events there, too. This year’s conference was held in the beautiful Okinawa at the Okinawa Institute of Science and Technology, one of Japan’s most international research centers I know of. I waited for this event both because I wanted to visit Okinawa once again and because it was my first in-person conference in four years. The conference lasted for two days. On the first day, we had a keynote speaker, flash presentations, a workshop, and a networking event in the evening. We had a panel discussion and a second workshop on the second day.

Why do organizations need communication teams?

This year’s keynote speaker was Ali Bailey, Director of Communications and Public Engagement at Francis Crick Institute. The institute has a versatile outreach program and not only shares its research with the scientific community but is also involved in educational programs and engagement with the non-scientific community. It also provides training for scientists to communicate their research. You may have read (and if not, you should!) Alexandra Bisia’s post about Francis Crick’s Cut + Paste exhibition. Ali Bailey’s talk was dedicated to the importance of science communication professionals. Professional science communicators are often met with a question:

Why do organizations or institutes need communication teams?

After all, people do communicate on a daily basis, what can be so difficult that it would require a communication team? And Ali Bailey shared one of her favourite answers:

Even though everyone has a bank account, organizations do prefer to have a professional financial team.

She then shared her career path and especially “the bad day in the office” experiences. I always admire people who share their mistakes. It is inspiring how people turn their mistakes into lessons. Her talk brought a beautiful message that science communication is a craft that requires time and perfection of skillset, not something you will be able to do overnight. I think that although obvious, it is an important reminder, as too often, I see that technological progress gives people the illusion that you can replace experience with automation. Although technology can make different processes more efficient, I also think knowing what you are doing is important to get a worthy result. 

Using podcasts for science communication 

After the keynote speaker, we had a workshop. There were two options, from which I chose “The Art and Science of Communicating Research through Podcasting” by Andrew MacIntosh, Associate Professor, Kyoto University (check his podcast here; he was lucky enough to interview Jane Goodall at some point!). I discovered podcasting some years ago, but I got into it only recently. As a person for whom talking is the main way to develop ideas, evaluate reality, and find solutions to problems, I have always wanted to try podcasting. There is something so simple and so mysterious about talking with people. Even when you think you know a person, talking to them often brings surprises. The logic or opinions you never thought could coexist. And if we are talking about a fluid and controversial topic such as science, podcasting seems like a natural way to deal with it. The workshop was really lightning speed. We had just enough time to listen to the basics and then develop and record the intro to a model podcast. It was a lot of fun! So, I hope to use these skills to do some science podcasting one day.

Flash talks: Sci-fi and STEM escape rooms

Flash talks at scientific conferences are always controversial to me. I see why they are there, but I am not sure they actually help. Risking stating the obvious, communicators are good at communicating😉, so their flash talks were informative and engaging despite the short time. I will share two of my favorite ones. The first was about using sci-fi to explain complex scientific ideas by Aileen Cooney, PhD Student at Tokyo Tech / Imperial College London. This inspired me to take “The Hitchhiker’s Guide to the Galaxy” from a bookshelf. For some reason, I never thought of sci-fi in that way. I thought of it as a kind of creative outlet from scientist to scientist, or at least people interested in science. The idea that we can use our imagination to create narratives that explain something real in an engaging manner was a surprise to me. Nevertheless, I fully agree with the speaker and made a mental note that if I ever try to be an author, sci-fi is where I can use both my writing and scientific knowledge to create something interesting and educational.

Another was about creating STEM escape rooms by Amanda Mathieson, Education and Public Engagement Manager, University College Dublin. Can you imagine? As a person who loves escape room games, I am thrilled at the possibility of using my knowledge in STEM to escape the room. I wonder how I can use tissue engineering or developmental biology in an escape room. It can be something more obvious, as an escape from a laboratory in the case of an accident; or it can be something more mysterious, connected to the development of the human brain, memories, and emotions! Either way, I hope this kind of escape room will become popular and that they will come to Japan!

The panel discussion “Many Worlds of Science Communicators.”

The panel discussion was facilitated by Heather Young, Vice President of Communication and Public Relations, Okinawa Institute of Science and Technology (OIST). The three amazing panelists were Chibuamam Ilechukwu (Founder, Hypertension Africa),  Charmaine Caparas (Communications Manager, Stockholm Environment Institute/ Chulalongkorn University), and Naoki Namba (Director of Public Relations & Communications Division, Hokkaido University/ Director/Professor, Hokkaido University). It was great to see science communicators with different backgrounds sharing how they ended up in this field, their challenges, and their hopes for the future. Charmaine Caparas shared insights from her extensive career in communication on some tough questions, such as “Should science writers be worried about AI?”. Chibuamam Ilechukwu talked about her fight against disinformation and lack of information and her quest to help people live healthier lives. Naoki Namba shared how he shaped his path toward science communication when it didn’t exist as a profession in Japan. When asked about his motivation for choosing science communication after receiving a master’s degree in life sciences, he said something that particularly spoke to me. What he liked about science was knowledge, the excitement of understanding something. But he didn’t care if he was the one who made the discovery or explained the phenomenon first.  

Using art to explain science

And finally, the last workshop. I chose “Illustrate to Educate: Simplifying Science through Art and Storytelling” by Nikitaa Sivaakumar, Founder and director of Wonder Yonder Research and Design Pvt Ltd. This was a challenging one! We had about 2 minutes to finish a drawing panel, each panel exploring a certain artistic trick to illustrate a piece of scientific information. The story we were illustrating was about the shape of the shinkansen (bullet train) head, which was designed after the beak of a kingfisher, and how this biomimicking helped to solve the problem of noise caused by airwaves pushed by the high-speed trains. Not only that, but we also got a couple of minutes of masterclass on how to do animation. The exercises were difficult, but they made me think about many things, as I have a bit of experience in creating simple animations to explain my research. And I am definitely practicing them again when I have a bit more time on my hands. One of the exciting ideas Nikitaa Sivaakumar shared was that when you try to explain complicated ideas, you can use drawings that are not perfect, maybe even intentionally simplistic. When you try to understand something you consider difficult, you don’t want to see perfect and complicated pictures; you would instead appreciate something that looks simple! Definitely check out the Wonder Younder Instagram!

And that’s a wrap! It’s amazing how many fascinating conversations you can have in the span of two days. I can’t wait for next year’s conference. But in the meantime, I hope this article will inspire anyone new to science communication to join a community. Here are some links to some of the communities I know:

• Already mentioned Japan SciComm Forum https://www.japansci.com/home

• National Association of Science Writers (USA) https://www.nasw.org/

• Association of Science Communicators https://community.sciencetalk.org/

• The European Federation of Science Journalism https://efsj.eu/

• The Global Network for Science Communication https://www.pcst.network/

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One does not easily pass up the opportunity to attend an ISSCR conference, especially when said conference is in Vienna, in the leadup to Christmas, and the venue is the Hofburg palace. I was really lucky, therefore, to have the opportunity to attend the meeting, held in Vienna this month, from 4-6 December. The theme of the meeting was “Elucidating Principles of Development with Stem Cells,” and boy, were those principles elucidated. With a suite of stem cells from various organisms available to developmental and stem cell biologists, research groups are now developing and refining ever more numerous and sophisticated ways to represent aspects of embryonic development with them. Accordingly, across the three days of the meeting, we were showered with a variety of talks covering every modality of -oid imaginable.

As suggested by the title of the meeting, a big focus was the use of stem cell-based or -derived models (with various -oid names, such as gastruloid, chimeroid, organoid, blastoid, cardioid, axioloid…). These are increasingly sophisticated and are being manipulated and studied in a variety of ways, and it is possible they may be able to supplement to a great extend the requirement for real embryos in research. I find it fascinating that we are now so familiar with the various signalling regimes that are required during different stages and in different tissues in development that it’s possible to replicate synthetically specific stages or tissues of development, starting from pluripotent stem cells (and sometimes extraembryonic stem cells too) – for example only preimplantation or post-implantation development, or axial elongation, or heart development, or neural tissues, or the gut. One of the many benefits of these systems is, of course, that these -oids can be reproducibly generated in great numbers, giving researchers an abundance of material on which to carry out experiments.

The inaugural talk of the meeting was delivered by Denis Duboule, an excellent speaker, whose lab’s extensive work on Hox genes is revealing increasing detail on the workings of the Hox cluster. Specifically, his lab has been using “stembryos” that recapitulate Hox gene expression along the anterior-posterior (or rostro-caudal) axis of the embryo. His use of a rope with interspaced knots and clothespins to represent Hox genes and the CTCF sites that ensure the sequential and appropriately-timed expression of genes along the cluster was a personal highlight. And it was still only 9:30 on the Monday!

The meeting had a strong showing of groups that work on ectodermal/neural tissue models. As someone who is not very familiar with these cell types from my own research, I was nonetheless impressed by how interesting I found them. Among others, there were talks by Paola Arlotta, Barbara Treutlein, Madeleine Lancaster, Thomas Vierbuchen, Anna Kicheva, Sharad Ramanathan, Elly Tanaka, Akanksha Jain, and Jürgen Knoblich. A topic which stood out for me was Joanna Wysocka’s talk on DNA-guided transcription factor cooperativity and its functions in cranial neural crest cells (CNCCs). Briefly, her lab identified a novel long consensus DNA motif, dubbed the “Coordinator,” containing a homeobox and an E-box binding motif. The Coordinator is specifically bound by the bHLH transcription factor Twist1 and homeobox factor Alx4. These interact only when bound to the Coordinator via a tiny segment of a loop only found on Twist1 and no other bHLH factors, thus promoting expression of a host of genes associated with CNCC behaviour.

Another talk on a much less common model organism was by Ali Elagoz, a doctoral student who works on the embryonic development of octopus nervous systems, in a broader effort to identify the evolutionary mechanisms by which cephalopods (octopuses, nautiluses, cuttlefish, and squids) have succeeded in evolving the largest nervous system of all invertebrates. For those not familiar with octopus nervous systems, you might be delighted to find out that only about 1/3 of octopus neurons are actually found in their brains, which, by the way, are wrapped around their oesophagus. Rapid reogranisation of the cephalopod genome and expansion of their suite of protocadherin genes may have contributed to the innovations that permitted the cephalopod brain to dramatically expand in size.

That said, fans of other germ layers were not disappointed, with talks on mesodermal and endodermal specification and derivatives by André Diaz from Universitat Pompeu Fabra (gastruloids), Sasha Mendjan (cardioids), Aryeh Warmflash (2D ESC patterning to study Wnt and Nodal/Activin signalling gradients), Cantas Alev (axial development), Katharina Sonnen (timing of somitogenesis), and Sarah Bowling (hematopoietic stem cells).

Another thematic arc highlighted during the meeting was the novel quantitative aspects that developmental and stem cell biology are being explored from, and which, until very recently, were almost exclusively assessed from a qualitative point of view. Ewa Paluch’s lab, for instance, is studying how epithelial-to-mesenchymal transition, a process essential in multicellular development, can be approached from the perspective of cell shape. Her lab has developed a “morphospace analysis” pipeline whereby cell shape is segmented and many variables quantified, finally undergoing dimensionality reduction to create a 2D “grid” of possible cell shape phenotypes. Cell shapes were then quantified before, during, and at the end of EMT, with cells undergoing EMT having a much “noisier” cell shape than epithelial cells, in other words exploring more of the morphospace. This suggests an instance of noise-driven transitions, where noise may actually help to overcome a barrier, in this case from an epithelial to a mesenchymal state.

Finally, I would be remiss if I didn’t highlight some methods development talks that really captivated me. Alexdander van Oudenaarden detailed a new method, developed by his postdoc Michael VanInsberghe, for profiling both single cells’ full complement of RNA (as single-cell RNA-seq already does), and their ribosome-bound RNA (like single-cell Ribo-seq) in a single experiment, in order to elucidate gene regulation at the transcriptional vs translational level. This is achievable by titrating MNase (micrococcal nuclease), an enzyme that can digest single-stranded nucleic acids, and that can function both as an endonuclease and exonuclease in a concentration-dependent manner. It’s amazing how such a simple concept can yield such rich data at the single-cell level!

I was also blown away by Kate McDole’s talk on imaging in developmental biology. Her unparalleled skills in custom-building microscopes are a boon to developmental and stem cell biologists who want to image samples that are rapidly growing, undergoing morphogenesis and constantly changing optical properties. Her “event-driven microscopy” platform is designed to assist users in imaging their organisms or organoids in a way that accounts for changes in the sample that are going to be happening in the future, without requiring the constant direct supervision of the user.

There was a broad and interesting array of posters at the meeting, and as always at a conference it was great to have the opportunity to meet researchers at all stages of their career, from many institutes and countries. As I mentioned, the venue was spectacular, and since it was literally a room in the former imperial palace, it was quite easy to become distracted by the numerous chandeliers, marble columns, and the stuccoed ceiling. As a bonus, every morning what I assume was a military band would parade past one of the windows, inadvertently serenading the first speaker of the day with some drumming.

Overall, the conference was a great experience. Nothing quite beats the excitement of hearing scientists talk about their work in person, especially about results that are often fresh out of the oven. And it’s always inspiring to meet new scientists with different interests and approaches to conducting research – you never know where a novel idea for your own work may come from, and which technique or new finding will form the basis for a new avenue of scientific exploration!

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A Press Release from Development

Infertility affects around 48 million couples worldwide and can have various causes. In mammals, including humans, eggs are produced in the ovary. When this process goes wrong, it can lead to female infertility. One example of this is premature ovarian insufficiency, which is characterised by problems with egg production before the age of 40. Up to 3.7% of females experience infertility as a result of this condition, and around 30% of cases are due to genetic variations. Professor Kehkooi Kee, from Tsinghua University, China, who helped lead the study, has been investigating this condition for several years. “In 2019, our collaborators, Professor Li’s team, encountered a family with premature ovarian insufficiency in which changes to a gene called Eif4enif1 appeared to be responsible for the disease,” said Professor Kee. The researchers decided to reproduce this genetic change in mice to try to understand how it affects human infertility. They show that the eggs of these mice are affected by changes to their mitochondria – the powerhouses of the cell – and publish this new discovery in the journal Development on 13 December 2023.

The researchers used CRISPR to introduce the genetic change in the mice. They allowed these mice to grow up and then compared their fertility with the fertility of mice whose DNA had not been edited. Yuxi Ding, the first author and a MD/PhD student who led the study, found that the average number of total follicles (the tiny sacs that contain developing eggs) was reduced by approximately 40% in older and genetically edited mice (the average pup number in every litter was reduced by 33%. Importantly, when grown in a dish, about half of the eggs that were fertilised did not survive beyond the early stages of development. This demonstrated that, just like the human patients, these mice were experiencing problems with fertility.

When the researchers studied the eggs from these mice under the microscope, they noticed something unusual about their mitochondria. Mitochondria produce the energy that cells, including egg cells, need. Mitochondria are usually evenly distributed throughout the egg, but the mitochondria in eggs from mice with the genetic variation were clustered together. “We were actually surprised by the differences in the mitochondria,” said Professor Kee. “At the time we were doing this research, a link between Eif4enif1 and mitochondria had not been seen before.”

It seems likely that these misbehaving mitochondria are contributing to the fertility problems in these mice, leading the researchers to propose that restoring proper mitochondrial behaviour might improve fertility. This study provides direction for future research in human infertility, such as establishing whether mitochondrial defects are also found in the eggs of human patients with premature ovarian insufficiency and whether these same mitochondrial defects are observed in embryos after the eggs are fertilised. In addition, testing whether restoring the normal distribution of mitochondria improves fertility could become a new treatment strategy. “Our research suggests that rescuing oocyte mitochondria abnormality could be a potential therapeutic target for clinical infertility patients with genetic variants,” says Professor Kee.

Ding, Y., He, Z., Sha, Y., Kee, K., Li, L. (2023). Eif4enif1 haploinsufficiency disrupts oocyte mitochondrial dynamics and leads to subfertility. Development, 150, dev202151. doi: 10.1242/dev.202151

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Throughout my years in science, I have been drawn to biological questions across scales and have been struck by how often they reflect aspects of societal phenomena. In this piece, I share with you some of my recent work, and how I view it as a lesson on how reductive or myopic definitions can overlook some of the most impactful discoveries and individuals in a collective.

Like many developmental biologists, I am fascinated by our bodies’ extraordinary cell type diversity. The genetic and epigenetic codes in each type of cell will dictate which unique sets of proteins are expressed. Until recently, the role of a large class of genes, now called micropeptides (or microproteins), was largely overlooked. Protein-coding genes were initially defined using a size cutoff of 100 codons; proteins smaller than that were assumed to not fold properly or carry out functions. Starting in 1990, we realized that this biased definition was filtering out potentially functional genes ^1–3. Partnered with technological advances, this shift in mindset has allowed the identification of thousands of small open reading frames (sORFs) that may encode functional tiny proteins.

In recently published work, my colleagues and I set out to investigate whether some previously identified long noncoding RNAs in fact encoded micropeptides ^4–6. Many of these RNAs were enriched in developing zebrafish brains and could represent uncharacterized small proteins that play important roles in vertebrate neurodevelopment. If this were the case, the loss of these micropeptides could manifest as behavioral phenotypes, a useful means of screening and prioritization. In this study, we showed that two previously identified long noncoding RNAs actually encode micropeptides with homology to a chromatin regulator found exclusively in vertebrates, called Hmgn1. In humans, this chromatin architectural protein is critically overexpressed in Down syndrome ⁷, and has been identified as a gene linked to autism ⁸. Through a series of behavioral, pharmacological, cellular, and molecular assays, we found that when these micropeptides were mutated, the gene regulatory networks that establish cerebellar cells and oligodendrocytes were most significantly affected. Intriguingly, these cell types were recently proposed to have appeared and evolved in jawed vertebrates ⁹. Is it possible that the emergence of these micropeptides co-evolved with the gene regulatory networks that established cerebellar and oligodendrocyte cell types in vertebrates ^10–12? This is yet an open question.

Recently, there has been a renewed urgency to understand the existence and vast possible functions of micropeptides, particularly in the brain ^13–15. Although there is evidence for thousands of putative micropeptides, the validation and characterization of these proteins will require high-throughput efforts across species, conditions, and cell types ¹⁶. Key implications from this field include identifying therapeutic or cell targets for neurodevelopmental diseases or disorders; engineering strategies for therapies directed towards de novo protein or drug design; and identifying molecular strategies for co-evolution of chromatin regions that harbor cryptic ORFs in physiologic, stressed, or disease neural states.

As I was working on this problem, I reflected on what drew me to my fascination with small proteins to begin with. I realized that the scientific question appealed to me because I saw myself and so many of my colleagues in this story. Consider the arbitrary limits placed on the definition of a protein. Evidence for, and acceptance of, changed definitions across fields has enabled a whole world of genes to now be deemed worthy of investigation. As such, this work comes at a time not only of scientific innovation, but also of social transformation. What are we missing when we limit our definitions to only the most dominant, visible, acceptable, status quo? What creativity has been ignored or stifled because it didn’t fit the mold? What are the outsized roles of the forces that shape creative strategies of survival – even thriving – and evolution?

This work also got me thinking about the evolutionary history of these micropeptides ¹⁷, and how gene networks and cell types may have co-evolved. Thinking about some of the ways that these micropeptide genes emerge, adapt, evolve, or disappear in different contexts provided me a lens through which to understand and confront some of the societal challenges that the life sciences – and academia at large – are, and have been, facing worldwide ^18–21.  Around the time I was wrapping up this work on micropeptides in zebrafish neurodevelopment ⁶, the NASEM report on “Advancing Antiracism, Diversity, Equity, and Inclusion in STEMM Organizations: Beyond Broadening Participation” was published ²¹. In particular, one section drew my attention:

“…the noteworthy ways in which [minoritized] individuals respond to bias in STEMM environments…can be categorized into three general groups: exiting the field, implementing strategies to fit in, and collectively mobilizing to transform the STEMM environment.” ²¹

How individuals respond to persistent, systemic biases in their environments – exit, adapt, or mobilize – is reflected in what often occurs in biological systems ^22,23. Our environments and lived experiences inevitably shape the scientific questions that we ask, how we ask them, and who gets to ask them. The confluence of this report and my own scientific journey highlighted to me how impossible it is to remove ourselves – the experiences and environments of the people doing the science – from the science itself.

So, what are the “micropeptides” in your own work, in your story? I iteratively reflect on these questions both as a basic (neuro)developmental biologist and as an emerging bioethicist ²⁴. As scientists, we can learn from the many unexpected discoveries regarding micropeptides – and any number of yet undervalued fields – to reimagine the tiny changes that can influence entire systems. When they are taken together, they’re not so small after all.

Acknowledgements

In reverse alphabetical order by first name (perhaps you can guess why from my own name), I am grateful to V. Greco, L. Grmai, L. Miao, L. Weiss, E. Strayer, C. Bartman, and A. Giraldez for feedback and/or workshopping through some of these ideas. I am supported by an award from the U.S. Eunice Kennedy Shriver National Institute of Child Health and Human Development (5K99HD105001).

Author Information

Valerie Tornini is currently an associate research scientist at Yale School of Medicine, and an incoming assistant professor in the Department of Integrative Biology and Physiology and the Institute for Society and Genetics at the University of California, Los Angeles (UCLA), USA.

References

1.         Benezra, R., Davis, R. L., Lockshon, D., Turner, D. L. & Weintraub, H. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell 61, 49–59 (1990).

2.         Ingolia, N. T., Ghaemmaghami, S., Newman, J. R. S. & Weissman, J. S. Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 324, 218–223 (2009).

3.         Slavoff, S. A. et al. Peptidomic discovery of short open reading frame–encoded peptides in human cells. Nat. Chem. Biol. 9, 59–64 (2013).

4.         Ulitsky, I., Shkumatava, A., Jan, C. H., Sive, H. & Bartel, D. P. Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution. Cell 147, 1537–1550 (2011).

5.         Bazzini, A. A. et al. Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation. EMBO J. 33, 981–993 (2014).

6.         Tornini, V. A. et al. linc-mipep and linc-wrb encode micropeptides that regulate chromatin accessibility in vertebrate-specific neural cells. eLife 12, e82249 (2023).

7.         Mowery, C. T. et al. Trisomy of a Down Syndrome Critical Region Globally Amplifies Transcription via HMGN1 Overexpression. Cell Rep. 25, 1898-1911.e5 (2018).

8.         Abuhatzira, L., Shamir, A., Schones, D. E., Schäffer, A. A. & Bustin, M. The Chromatin-binding Protein HMGN1 Regulates the Expression of Methyl CpG-binding Protein 2 (MECP2) and Affects the Behavior of Mice. J. Biol. Chem. 286, 42051–42062 (2011).

9.         Lamanna, F., Hervas-Sotomayor, F. et al. A lamprey neural cell type atlas illuminates the origins of the vertebrate brain. Nat. Ecol. Evol. 7, 1714–1728 (2023).

10.       Zalc, B. The acquisition of myelin: An evolutionary perspective. Brain Res. 1641, 4–10 (2016).

11.       González-Romero, R., Eirín-López, J. M. & Ausió, J. Evolution of High Mobility Group Nucleosome-Binding Proteins and Its Implications for Vertebrate Chromatin Specialization. Mol. Biol. Evol. 32, 121–131 (2015).

12.       Deng, T. et al. Interplay between H1 and HMGN epigenetically regulates OLIG1&2 expression and oligodendrocyte differentiation. Nucleic Acids Res. 45, 3031–3045 (2017).

13.       Mudge, J. M. et al. Standardized annotation of translated open reading frames. Nat. Biotechnol. 40, 994–999 (2022).

14.       Sandmann, C.-L. et al. Evolutionary origins and interactomes of human, young microproteins and small peptides translated from short open reading frames. Mol. Cell 83, 994-1011.e18 (2023).

15.       Duffy, E. E. et al. Developmental dynamics of RNA translation in the human brain. Nat. Neurosci. 25, 1353–1365 (2022).

16.       Tornini, V. A. Small protein plays with big networks. Trends Genet. TIG S0168-9525(23)00236–6 (2023)

17.       Weisman, C. M. The Origins and Functions of De Novo Genes: Against All Odds? J. Mol. Evol. 90, 244–257 (2022).

18.       Thorp, H. H. It matters who does science. Science 380, 873 (2023).

19.       Maina, M. B. African neuroscience: Desperately seeking diversity. UNESCO Cour. 2022, 15–16 (2022).

20.       Silva, A. et al. Addressing the opportunity gap in the Latin American neuroscience community. Nat. Neurosci. 25, 1115–1118 (2022).

21.       National Academies of Sciences, Engineering, and Medicine. Advancing Antiracism, Diversity, Equity, and Inclusion in STEMM Organizations: Beyond Broadening Participation. (The National Academies Press, 2023).

22.       Montgomery, B. L. Lessons from Plants. (Harvard University Press, 2021).

23.       Montgomery, B. L. Lessons from Microbes: What Can We Learn about Equity from Unculturable Bacteria? mSphere 5, e01046-20 (2020).

24.       Tornini, V. A., Peregalli Politi, S., Bruce, L. & Latham, S. R. Maximizing biomedical research impacts through bioethical considerations. Dis. Model. Mech. 16, dmm050046 (2023).

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The webinar on 5 December 2023 was on the topic of germ cell development and was chaired by Development Editor, Swathi Arur (MD Anderson Cancer Center). Below are the recordings of the talks.

Gabriele Zaffagnini (Centre for Genomic Regulation)

Diego Sainz de la Maza (University College London)

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Where is the lab?

In the middle of the Aix-Marseille University Campus, at the heart of the Calanques National Park, at the border of city. The most beautiful academic spot in France ;)

Lab website: Neural stem cell plasticity – IBDM | Institut de Biologie du Développement de Marseille (univ-amu.fr)

Research summary

We are mainly investigating temporal patterning, and how it links development with regeneration and pediatric cancers. Along the years, we have identified key factors that are sequentially expressed in the embryo and that are important to ensure that developmental programs unfold with the correct timing. We have found that failure to do so can lock tissues into permanent development leading to aggressive tumors. This mechanism likely underlies the emergence of pediatric cancers. We are therefore working on the various mechanisms that regulate temporal transitions during development or that coopt temporal patterning to promote regeneration 💪🏻 or pediatric cancers 😫. Our model organisms are Drosophila and the chick embryo.

Lab roll call

Cédric: As a PI,my everyday work consists in making sure that everybody is happy to come in the lab every morning to make exciting science.

Dylan: I joined Cedric Maurange’s team as postdoc to understand how miRNAs can regulate the cellular composition, hierarchy, and growth of pediatric tumors in an established Drosophila cerebral tumor.

Paul: I am the team bioinformatician, working as a research engineer on deciphering how the cell-of-origin affects the differentiation trajectory of rhabdomyosarcoma.

Lauranne: As a non-permanent engineer, I investigate how MYCN or c-Myc overexpression perturbs cell lineage progression and cerebellum’s organization by using chick embryo as study model.

Shobana: I am a PhD student in the team investigating the dynamic role of microRNAs in neuronal maturation in Drosophila

Emma: I am a PhD student working on the self-organizing principles governing tumor growth and I am using a model of Drosophila brain tumor as well as a numerical model of tumor growth.

Favourite technique, and why?

Cédric: I am very interested in single-cell techniques. It was such an amazing moment when my student came with our first single-cell RNA-seq data, back in 2017, which so clearly showed the cellular heterogeneity of neuroblast tumors and how temporal programs are recapitulated in them. It became clear that this technique would be key to unravelling how cellular heterogeneity and hierarchy are regulated in cancer.

We are now trying to use single-cell multiomics combined with computational simulations to decipher how perturbed developmental/temporal trajectories can be corrected in tumors. I am very grateful to the mathematicians and computer scientists who enable us to make sense of these complex datasets.

Apart from your own research, what are you most excited about in developmental and stem cell biology?

Cédric: In general, the ability to measure/visualise a biological process at the single cell level, but in the context of a tissue, is really exciting. At the moment, I am particularly excited about the possibility of precisely measuring the transcriptional activity of a gene at a given developmental time in a single cell and correlating it with its chromatin environment. Self-organisation at all molecular and cellular scales is also fascinating, particularly challenging and attractive because understanding it will require the collaboration of biologists, mathematicians, physicists and computer scientists.

How do you approach managing your group and all the different tasks required in your job?

Cédric: Science should be about passion and fun. People in the lab should be self-motivated. There are so many mysteries to be solved in biology, it is easy to pick up one that you are particularly interested in and contribute to solve it. It is very fascinating also to see where the quest leads us.

I like to give time to newcomers in the lab so that they get familiar with the model and take ownership of the project. Hopefully, after some time they will also come with new ideas of how to tackle the problem. We have weekly lab meetings and my door is always open (except when I am on Zoom !). I expect people to naturally come to me when they want to discuss. We frequently do one-to-one meetings to more precisely assess the current situation and which points to concentrate on. We also have a growing number of projects that relies on tight interdisciplinary collaborations. The combined expertise is usually a talisman for the unexpected.

What is the best thing about where you work? 

Cédric: The good atmosphere, the multi-disciplinarity of the institute and the multiple possibilities of collaborations with the other institutes on the campus and throughout the city – everything in a fantastic natural environment and sun all year long.

Dylan: Working in the calanques national park, the Luminy campus site is exceptional.

Paul: The good atmosphere and the possibility to work with scientists with really various research fields and interests. Moreover, the lab and the scientific community of Marseille also offer many social events.

Lauranne: We work in a lovely campus surrounded by nature where the positive atmosphere among the 21 IBDM’s teams not only during work hours but also during after- work gatherings adds to the overall pleasure and satisfaction we find in our work environment.

Shobana: In addition to the institute being multi-disciplinary, the friendly and engaging atmosphere makes it easy to approach people for help or discussion, further facilitated by regular seminars and after-work sessions.

Emma: The IBDM, ideally located in the calanques national park, benefits from the very nice weather of Marseille all year long. Moreover, the institute gathers many people from different backgrounds which makes it very interdisciplinary in addition of the nice and friendly atmosphere.

What’s there to do outside of the lab?

Cédric: Walk in the Calanques and discover the various landscape of Provence, enjoy all the activities of the vibrant city that is Marseille.

Paul: The lab is ideally placed in the “Parc National des Calanques”, a sort of nature spot in the periphery of the big city of Marseille, offering the possibility to do some hiking. In the city center, there are some museums, malls etc. and during winter, a beautiful Christmas market on the Vieux-Port.

Shobana: There’s tons to do right outside the lab like hiking, climbing or just walking. Even looking out of the lab window, one can see how beautiful and serene it is being surrounded by the Calanques. A well-equipped sports complex is quite nearby as well, offering training in different sports.

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“We knew back in the late 1960s that half the human genome was repetitive DNA. And so, where did this myth arise that those scientists were incredibly stupid? I mean, these guys, Jacob and Monod, they got a Nobel Prize!”

Prof. Larry Moran, author of What’s in Your Genome? Why 90% of your genome is junk

In the latest episode of the Genetics Unzipped podcast, we discover how 500,000 whole genomes will help medical research, plumb the depths of the ‘dark genome’, and ponder how much of our DNA is just junk.

Genetics Unzipped is the podcast from The Genetics Society. Full transcript, links and references available online at GeneticsUnzipped.com.

Subscribe from Apple podcasts, Spotify, or wherever you get your podcasts.

Head over to GeneticsUnzipped.com to catch up on our extensive back catalogue.

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

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