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The shrimp Parhyale hawaiensis – a non-model organism research story with Dr. Michalis Averof

Posted by , on 28 April 2024

Picture of Dr Michalis Averof

Earlier this year, my co-correspondent for the Node Brent Foster and I published a pot pourri-style interview article asking biology researchers about their work with non-model organisms (NMOs). As they all had many fascinating details and insights to share about their work with their respective NMOs, we decided to publish the full interviews as well. Below is the interview with Dr Michalis Averof, whose lab works on the shrimp Parhyale hawaiensis at the Institut de Génomique Fonctionnelle de Lyon in France.

Could you give me a three sentence introduction to what you do?

In the lab we study almost exclusively regeneration using this small crustacean [Parhyale hawaiensis] as our model. Τhe origin of the lab is evo-devo. Ever since my PhD, I was interested in comparative developmental biology, in what different organisms can tell us about mechanisms of development and how those mechanisms evolve. This is how we started to work with crustaceans, which I have been working with since then. Then gradually regeneration, which was a side project, became our main focus.

Does Parhyale exclusively regenerate its limbs?

Yes, as far as we know it is the only structure that arthropods can regenerate, basically the appendages.

What are the benefits and the specific challenges of using crustaceans as an organism of study?

There are two reasons for starting to work on a new organism, let’s say on regeneration. The first one is the evolutionary interests. Regeneration is a process that is widespread in the animal kingdom. There are also many species that don’t regenerate. And it’s still an open question to what extent this is an ancient capacity that all animals inherited from their ancestors, which was lost here and there, or a capacity that has emerged during evolution multiple times. The evolutionary dynamics of this process are not well understood at all. Studying different groups of animals allows us to make comparisons and to see to what extent animals use similar mechanisms to achieve this. Hopefully, as we accumulate more information from different branches of the tree of life, a picture will emerge. I have to say, so far, no clear picture has emerged. It’s still not clear how regeneration has evolved and what the earliest origins were. But that’s one motivation for starting [on] a new model.

The other motivation is that sometimes moving into a new system gives you new possibilities, new experimental opportunities. Our animal, for example, is a very bad system to pick if you wanted to do a genetic screen like you would do in C. elegans or in flies. But it turns out that it’s a very good system if you want to image what happens during regeneration. You can image the whole process [at] cellular resolution from beginning to end. So individual organisms, because of technical advantages mostly, offer new opportunities. In this case, the reason why we can image regeneration so well is that these animals as adults are transparent. They’re small enough that we can just image through their legs with a confocal microscope. We can make transgenics so we can label the cells; and we can immobilise them, which can be a big challenge [in other organisms]. With embryos, you can put an egg under a microscope, and it will mostly stay there, and you can do live imaging. With a regenerating adult, this is very difficult. You cannot anaesthetise a zebrafish for an entire week without killing it. In our system [though], what allows us to [image the entire process of regeneration], is the fact that arthropods are encased in a chitinous exoskeleton. We can use simple surgical glue to stick those animals on a cover slip. And they will stay there, they can’t go away until they molt. This is a small, technical thing that makes the system suitable for live imaging. And unless you have an animal that is surrounded by cuticle, it’s very difficult to find a way to do that.

It’s small features like that which make different model organisms valuable and provide new opportunities. The other thing to keep in mind is that regeneration is a process that is very poorly represented in the best models that we have. Mice, flies, C. elegans are very poor at regenerating. So in general, we don’t have great genetic models for regeneration. Zebrafish is the only exception to that.

Was that the motivation to move into the more regenerative aspect of studying Parhyale?

The motivation was simple curiosity. We had developed genetic tools, such as transgenics, we could overexpress genes, and we could label cells with GFP. We had developed these tools for other reasons; at the time, we were studying Hox genes and how they contribute to body plan evolution in the arthropods. That was the reason for generating those tools. But once we had them, it became possible to visualise what is happening. So it was a rather opportunistic thing. Often, you see something that is interesting, and you are drawn in that direction.

So getting into studying crustaceans, was there something that convinced you that they’re really special or as you say, was it more of a chance path?

I was convinced they’re special before, when I was studying evolution. Crustaceans are the closest relatives to the insects, but they have very different body plans, a different organisation of segments in their bodies. So it was an attractive group for studying body plan evolution, how segmental specialisations evolve, and whether the Hox genes might be driving those changes. So that was the reason for going into crustaceans, they were very attractive for that reason. Then, as I said, moving to regeneration was rather serendipitous, because of the tools we had already made and the fact they’re transparent.

How was the discovery made about limb regeneration? 

It’s been known for a long time that many crustaceans and other arthropods have the capacity to regenerate their legs. There were some classic studies in the 70s that were using cockroaches as models for studying regeneration.

In a similar vein, then, is there at the tip of your tongue a study in Parhyale that you think is really interesting, that you would recommend to someone if you wanted to get them interested in this model organism?

I’m not sure there is a big breakthrough that has been made in Parhyale yet. I think it’s exciting to be able to see the process of regeneration, that is quite unique. Usually you see snapshots, because it takes very long, it takes weeks or months in some organisms. Having the continuous process on time lapse, where you can see how individual cells are actually behaving and dividing is very exciting, even though in terms of understanding the process, it has not really yet revolutionised the way we see things. There is no paper where I would say, this is a big discovery we’ve made in Parhyale which was very unexpected, and it changed our views.

You have to realise it’s a very small community, there are maybe 20 or 30 people working on the animal. So there’s not so much history and so much that has been done on them. But it’s nice that you have different groups of people with different interests coming in. One of the latest papers to come out this year in Current Biology is [by] people who study biological rhythms, and have studied how Parhyale regulate their daily activities in relation to tides. Our animal is an intertidal species, and it seems it has an endogenous clock that runs with the tidal cycle rather than with a day-night cycle. Well, they have both, but somehow the two interact in a complex way.

Is this something that you can disrupt by removing them from their native tidal environment and putting them in a tank in a building?

Yes. When we keep them here in tanks, we don’t really give them an artificial tide. People who study circadian rhythm had noticed that there were two peaks of activity, one in the morning and one in the evening. And the intertidal cycle is a little bit longer than 12 hours. So that might reflect the fact that they have a 12-hour cycle rather than a 24-hour cycle. But of course, in nature, the tidal cycle comes slowly out of sync with the day-night cycle. And that is not observed in the lab.

It’s exciting that people are beginning to study phenomena that were not accessible before in the standard models, like tides and regeneration. There are new aspects of biology that become accessible once you have a new system.

Considering this community is so small, and considering that the genome of Parhyale might not be as familiar, maybe there’s not 15 different genome iterations like there are for the mouse, how does data analysis and data sharing between these labs work? And what are the interactions like?

You would imagine that small communities are very well interconnected. We are connected, but not very tightly. I think it mostly has to do with the fact that we are on different continents and we study different questions. We talk to each other and we share tools and genetic resources. For example the genome sequencing and assembly was a collective effort.

We all use the same population of Parhyale. It’s a population that has been kept in the lab for more than 20 years. There are a few people beginning to isolate new populations from the wild. The funny thing about the population we share is that it was picked up in an aquarium in Chicago, about 20-25 years ago, and we don’t know which part of the world it came from originally.

It was a pest in the Chicago aquarium. And since Parhyale hawaiensis has been described to be a tropical species that lives all around the world, from Hawaii, to Brazil, to India, we don’t actually know where that particular population came from. We all use it, the genome has been sequenced from, and all our transcriptomic work is based on, that population. Those are the kinds of genomic resources that we all share.

For transgenesis and CRISPR, we more or less use the same protocols. We don’t share transgenic lines so often, but that’s mostly because we have different interests, and each of us develops our own lines for the particular questions we’re asking. The other issue is, we haven’t yet figured out an easy way of sending these animals across the world without having problems with customs. That is a bit of a barrier.

On the other side, as there are so few people working on shrimp, I assume that there’s only one person per department per University per country. Is it difficult to engage with people working on other things? How useful do you find it?

It’s not difficult because each of us belongs to different scientific communities. It’s not that you have to work on the same species to engage with people. The regeneration community, for example, is very large. We talk to that community, we talk to the evolutionary biology community. Even though I have worked with crustaceans, I was always close to the Drosophila developmental biology community. The labs where I did my PhD and my postdoc were fly labs. We don’t feel lonely. We are more isolated in terms of technology, in the sense that for every project, we have to develop our own tools, there isn’t this big community behind you generating Gal4 drivers or Cre lines that are shared, like you have in other systems. When you start a project, you have to generate those tools by yourself. And that is a major limitation when working with our kind of peripheral models. The critical mass of the community is important for generating and sharing tools, and we don’t have that.

Would you say it takes a slightly more adventurous researcher to decide to go down that path?

Definitely, it takes a different kind of researcher. To work with these animals, you have to realise that research is going to move much forward more slowly, because you will have to start many things from scratch. The benefit, on the other side, is that in almost anything you study, you’re going to make new discoveries, because no one has studied that before. So you’re entering a virgin field. It takes a lot of effort to discover something, but whatever you discover is new knowledge. You have the opportunity to shape your research field to a larger extent.

Thank you very much. Is there anything else you’d like to add?

Perhaps I should tell you what my motivation behind all this is, besides the specific questions that we’re asking. Biology has focussed on model organisms for very good reasons, because model organisms give us the tools to go deeper and to study mechanisms. But, over the years, we have developed this idea that model organisms will reveal universal mechanisms, and that we can study most of biology through the model systems that we have chosen.

But I am convinced that there is an enormous amount of biology that we are missing, if we rely only on the established models. There are simply biological phenomena which are not represented in this handful of organisms. Regeneration is partly one such example. But there are other topics, like developmental plasticity, where you have different casts of animals that develop depending on the environment, there are no established genetic models for that kind of study. There are organisms that eliminate half of their genome in somatic cells, they break their chromosomes apart and shed half of the genome during development, and they only keep the full complement in the germline. There is a significant number of organisms, spread all around the tree of life, that do that. There is no way to access this kind of phenomenon and to understand its importance in established models. I see these like new continents of biology that are still unexplored. New model organisms will allow us to explore these. Of course, it’s going to be difficult, and it’s going to take time, and it’s going to take development of tools. But that’s for me the major motivation for going into different systems, because I think there’s biology that we haven’t discovered yet.

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An interview with Marco Podobnik, GfE PhD award winner 2024

Posted by , on 25 April 2024

Photo credit: Gerard Hynes

The 2024 German Society for Developmental Biology (GfE) PhD award recipient was Marco Podobnik, who worked on pigment pattern diversification in Danio fish species at the Nüsslein-Volhard laboratory in Tübingen. We caught up with Marco to learn more about his background, his PhD work and his research interests as a postdoc at the Australian Regenerative Medicine Institute.

First of all, congratulations on receiving the 2024 GfE PhD award! What does this award mean to you?

Thank you. I am only half-way joking when the first thing that comes to my mind is, hey, now I can fill out the line that asks for “prizes” in grant applications. Being recognized by the German Society for Developmental Biology is a huge honour. The fact that my work was so collaborative makes it important to draw the attention to my colleagues I worked with over the years. The Max Planck Society creates permissive environments for basic research we conducted, a privilege I am aware of. I wish these opportunities would be more accessible.

Let’s go back to the beginning. When did you first become interested in science?

I believe the way we construct stories of the scientific process is a symptom of the humane desire to tell good stories. This also applies to the story of people’s life history. When I was a kid, I always liked to be out in the forests, trying to identify birds by their sounds. Although I was never really excited about maths, I deliberately chose all science subjects in high school. I had an excellent chemistry teacher, Holger Mummert, who did his PhD in Tübingen. In my final year I joined his class on fossils which I found beautiful. I had to become a biologist, right?

How did you come to do a PhD at the Nüsslein-Volhard laboratory?

I think this destination was the consequence of a random process paired with a developing passion. When I still studied biology at the University of Cologne, I had to find a lab for an internship. So I made a list with shiny labs working on topics I mostly never heard of and brought it to my mentor, Matthias Hammerschmidt. He had done his PhD with Christiane (Janni) Nüsslein-Volhard in Tübingen. In the early 1990s, he participated in the genetic screens in zebrafish [1], a heroic effort approaching the Nobel Prize work in flies in the 1980s [2]. When I showed Matthias the list, he smiled and refused to send me anywhere. Instead, he offered me to take a look into his zebrafish lab. Seeing live zebrafish embryos under a stereomicroscope for the first time was quite a fascinating moment. After that he suggested me to go to the Max Planck Institute for Developmental Biology in Tübingen (now the MPI for Biology).The real deal was the weekly meetings in Janni’s small office, where everybody had to hunch shoulders to fit in. Tiny zebrafish summits regularly joined by Patrick Müller who led a group at the Friedrich Miescher Laboratory next door.

Back in Cologne I obtained my undergraduate degree with Sigrun Korsching, who had been a junior group leader in Tübingen before she established her zebrafish lab in Cologne. At some point Uwe Irion offered me a PhD position in Janni’s lab. I had just come back from two expeditions with other students from the Cologne University on microbial communities in South America and in the North Atlantic Ocean. Biodiversity and development were (and still are) exciting to me, so I chose to work with Uwe on pigment patterning in other Danio species originally coming from Southeast Asia.

Can you summarise your PhD research?

Although Janni’s lab had always been interested in Danio species other than the zebrafish [3, 4], the pioneering work came from David Parichy and colleagues over the last two decades [5, 6]. A milestone was the release of a reliable phylogeny of the genus by Braedan McCluskey and John Postlethwait [7]. I found it fascinating that species most similar in their pigment patterns were not necessarily most closely related, and most closely related species often had most divergent patterns. Zebrafish develop a striking pattern of horizontal blue and golden stripes, while the sister species D. aesculapii conceals itself by forming dark vertical bars that are low in contrast. Given the knowledge about the genetic basis of stripe formation in zebrafish, maybe we could identify the genes that functionally diverged to contribute to patterning differences between species.

We decided to focus on genes that code for proteins mediating direct cell-cell contacts. Uwe had already generated mutants in a handful of these genes and acquired a number of Danio species; a collection I helped to make more comprehensive. We were inspired by the reciprocal hemizygosity test to identify diverged genes and we could meet the requirements to apply it, namely generating null mutants in species and hybrids between species [8]. Such an endeavour in non-model organisms was unthinkable without the CRISPR/Cas9 system, which the lab aims to improve since its adaptation for genetic engineering [9, 10]. Uwe and I started an extensive effort of making hybrids, pairing wild-type and the newly generated mutant species in various combinations. Four years later it all came together: While some genes remained functionally conserved, others diverged across the phylogeny [11].

In the case of the potassium channel gene kcnj13 we identified a repeated and independent functional divergence; this contributed to patterning differences between zebrafish and D. aesculapii [12]. We found that the black melanophores require the kcnj13 function to acquire certain cell shapes within their own population but they also instruct the two other pigment cell types, yellow/orange xanthophores and shiny/blue iridophores, to change their shapes according to their location in the skin. As the D. aesculapii allele is functionally different from the zebrafish one, we propose that divergence in kcnj13 caused changes in the way the pigment cells interact and change their shapes to contribute to the species-specific differences in colour and contrast of the patterns [13].

Your PhD research involves working with a wide range of techniques. Do you have a favourite?

I love genetics for its power to let us understand processes across different levels of biological organisation. During university I learnt about Muller’s classification of alleles [14]. It was beautiful to see how it could be used when we studied pattern development in hybrids between Danio species. The altered patterns in hemizygous hybrids between mutant zebrafish and wild-type D. aesculapii indicated that the kcnj13 allele from D. aesculapii behaves like a hypomorph as it could not compensate the CRISPR/Cas9-induced loss-of-function of the D. rerio allele. The patterns of hemizygous hybrids from the reciprocal cross are similar to the patterns of hybrids between wild-type species. Thus, the wild-type alleles from zebrafish and D. aesculapii cannot be functionally equivalent. Initially we thought that the D. aesculapii allele had lost its function completely but mutant D. aesculapii indicated that the gene function was still required for patterning. I love discovering obvious phenotypes in mutants, as it can be a rare but very profound experience. The suitability of zebrafish for fluorescence imaging in vivo makes it a fantastic model, as you can see cells behaving in real time, sometimes even with subcellular resolution. I can probably make the most meaningful contributions by applying a duet of genetics and in vivo imaging. Often the successful outcome of any experiment relied on the groundwork and expertise of my colleagues. I essentially understand science as teamwork.

Speaking of teamwork, how was your experience collaborating with people across the world for your PhD work?

As you can imagine pigment patterning is a relatively small field, although it hopefully becomes apparent how exciting it is. It’s great that people with expertise in genetics, sequencing methods, protein structure modelling and image analysis collaborate on this topic. I feel there aren’t really boundaries when it comes to common interests and curiosity, it’s just essential to bring passionate people together. It’s important to communicate effectively and to make it fair for the people involved. When it comes to generating ideas, bigger meetings might not always be effective. The most creative ideas emerged during our small lab and one-to-one meetings.

Were there any frustrating times during your PhD? And on the flip side, any particularly memorable moments?

My most exciting moments were the ones when we made discoveries in the lab. Sometimes it took a while to realize them. It requires one to think about observations over and over again. We were all working a lot, basically every day including most weekends, which is an intensity I have decided to reduce. I have fond memories of the garden parties in summer and the yearly Christmas cookie baking at Janni’s house.

You’ve recently moved across the globe to do a postdoc in Melbourne. How was the experience and what motivates your research today?

The Melbourne metropolitan area is a great place for personal life and research, although it can be depressing to think about the fate of the traditional owners of this country. The Australian Regenerative Medicine Institute cultivates broad interests in development, regeneration, evolution and medicine. Our lab headed by Peter Currie explores muscle biology using a spectacular diversity of fish models. It’s stimulating to be part of a bigger team. I find it exciting to help others with their projects, while I am defining my own long-term goals.

Finally, let’s go outside of the lab. What do you like to do in your spare time?

I play the saxophone in various settings for over 20 years now, which is tremendously important to me. I also love hiking. A very memorable trip was the Via Alpina in Switzerland and now very recently a trip to the Victorian Alps in Australia.

Photo credit: Viola Brand

Dr. Marco Podobnik
Research Fellow
Australian Regenerative Medicine Institute, Monash University, Clayton 3800 VIC, Australia

X: @m_podobnik

Website: https://marcopodobnik.wordpress.com/

References

1.         Nusslein-Volhard, C. (2012). The zebrafish issue of Development. Development 139, 4099-4103.

2.         Wieschaus, E., and Nusslein-Volhard, C. (2016). The Heidelberg Screen for Pattern Mutants of Drosophila: A Personal Account. Annu Rev Cell Dev Biol 32, 1-46.

3.         Singh, A.P., and Nusslein-Volhard, C. (2015). Zebrafish stripes as a model for vertebrate colour pattern formation. Curr Biol 25, R81-R92.

4.         Irion, U., and Nusslein-Volhard, C. (2019). The identification of genes involved in the evolution of color patterns in fish. Curr Opin Genet Dev 57, 31-38.

5.         Parichy, D.M., and Johnson, S.L. (2001). Zebrafish hybrids suggest genetic mechanisms for pigment pattern diversification in Danio. Dev Genes Evol 211, 319-328.

6.         Patterson, L.B., and Parichy, D.M. (2019). Zebrafish Pigment Pattern Formation: Insights into the Development and Evolution of Adult Form. Annu Rev Genet 53, 505-530.

7.         McCluskey, B.M., and Postlethwait, J.H. (2015). Phylogeny of zebrafish, a “model species,” within Danio, a “model genus”. Mol Biol Evol 32, 635-652.

8.         Stern, D.L. (2014). Identification of loci that cause phenotypic variation in diverse species with the reciprocal hemizygosity test. Trends Genet 30, 547-554.

9.         Irion, U., Krauss, J., and Nusslein-Volhard, C. (2014). Precise and efficient genome editing in zebrafish using the CRISPR/Cas9 system. Development 141, 4827-4830.

10.       Dorner, L., Stratmann, B., Bader, L., Podobnik, M., and Irion, U. (2024). Efficient genome editing using modified Cas9 proteins in zebrafish. Biol Open 13.

11.       Podobnik, M. (2023). On the Genetic Basis of Pigment Pattern Diversification in Danio Fish, (Eberhard Karls Universität Tübingen).

12.       Podobnik, M., Frohnhofer, H.G., Dooley, C.M., Eskova, A., Nusslein-Volhard, C., and Irion, U. (2020). Evolution of the potassium channel gene Kcnj13 underlies colour pattern diversification in Danio fish. Nat Commun 11, 6230.

13.       Podobnik, M., Singh, A.P., Fu, Z., Dooley, C.M., Frohnhofer, H.G., Firlej, M., Stednitz, S.J., Elhabashy, H., Weyand, S., Weir, J.R., et al. (2023). kcnj13 regulates pigment cell shapes in zebrafish and has diverged by cis-regulatory evolution between Danio species. Development 150.

14.       Muller, H. (1932). Further studies on the nature and causes of gene mutations. Jones DF, ed. In Proceedings of the 6th International Congress of Genetics. pp. 213-255.

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Who was Rita Levi-Montalcini?

Posted by , on 22 April 2024

Rita-Levi Montalcini (1909-2012) was an Italian neurobiologist who lived an extraordinary life, and today (22nd April) would have been her 115th birthday. Click on each image to enlarge and read more about her…

Image credit:
Premio Internazionale “Wendell Krieg Lifetime Achievement Award” a Rita Levi Montalcini – 30 settembre 2009” by unipavia is licensed under CC BY-NC-SA 2.0.

Sources:
Coutinho, L. and Teive, H.A.G. (2023) ‘Rita Levi-Montalcini: the neurologist who challenged fascism’, Arquivos de Neuro-Psiquiatria, 81(1), pp. 95–98. Available at: https://doi.org/10.1055/s-0043-1761426.

Hamburger, V. and Levi-Montalcini, R. (1949) ‘Proliferation, differentiation and degeneration in the spinal ganglia of the chick embryo under normal and experimental conditions’, Journal of Experimental Zoology, 111(3), pp. 457–501. Available at: https://doi.org/10.1002/jez.1401110308.

Malerba, F. (2022) ‘Why Are We Scientists? Drawing Inspiration From Rita Levi-Montalcini’, Frontiers in Cellular Neuroscience, 15, p. 741984. Available at: https://doi.org/10.3389/fncel.2021.741984.

The Nobel Prize | Women who changed science | Rita Levi-Montalcini. Available at: https://www.nobelprize.org/womenwhochangedscience/stories/rita-levi-montalcini (Accessed: 19 April 2024).

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Lab meeting with the Koltowska lab

Posted by , on 18 April 2024

Where is the lab?

You can find us in Uppsala, Sweden!

Lab website: https://koltowskalab.com/

Research summary

Here in the Koltowska lab, we are interested in all things lymphatic vessel-related. How lymphatic endothelial cells (LECs) are specified, gain their identity, end up in the right place to form vessels, and how these vessels function.

Lab roll call

Hannah Arnold has been a postdoc in the lab for five years and is interested in lymphatic development, focusing on how LECs migrate and interact to navigate their environment.

Marleen Gloger has been a postdoc in the lab for five years as well and is interested in lymphatic vessel development, specifically LEC cell proliferation, and how these processes are altered in disease conditions such as cancer and metastasis formation.

Di Peng has done a PhD in the group and now continues as a postdoc. She is very fond of observing cellular events during development using different live imaging techniques. Her projects focus on regulation of lymphatic endothelial behaviours. 

Faidra Voukelatou has recently started her PhD in the group and is interested in cancer as well as lymphatic vessel research. She enjoys working with zebrafish as an animal model to investigate the dynamics of brain cancer invasion and vasculature.

Renae Skoczylas has been a research engineer in the lab for 6 years and enjoys all things zebrafish and lymphatics.  She is particularly happy generating new mutant lines for the lab using CRIPSR technology and being involved in and helping with any other lab members’ projects.

Favourite technique, and why?

Kaska Koltowska: Microscopy! There is something incredibly magical in looking down the microscope and observing life in high magnification. Using microscopy to look at zebrafish heartbeat and blood flowing through the vessels never stops to amaze me!

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

Kaska Koltowska: I think how gene expression is regulated and the steps coordinating cell specification is incredibly fascinating. The level of developmental reproducibility in every embryo is just mind-blowing. Biology gets it right almost every time, and if it does not, we can learn something very important.

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

Kaska Koltowska: I don’t think I use any specific managing tools. I dedicate time to discussing science with every member of the group regularly. This helps to keep the projects focused. When a project is coming up close to completion I dedicate more time for it. It helps a lot that the team is very efficient and group members can manage themselves very well so my input is minimal. For myself, I often make a weekly prioritisation plan of the most important tasks that need to be done that week and try to stick to it.

What is the best thing about where you work? 

We are positioned between two wider communities. That of Vascular Biology, where our lab is located and encompasses ten research groups, and the Uppsala Zebrafish community where our fish are housed alongside five other groups and one service platform.

What’s there to do outside of the lab?

Uppsala is a small but busy student city where you can enjoy restaurants and cafes for a ‘fika’ break. It is located close to nature giving us the opportunity to enjoy the forest for a walk or BBQ in the summer and snow sports in the winter. It also provides an excellent backdrop for walking the boss’ dog. On the other hand, Uppsala is a short train ride to Stockholm so it is easy to enjoy big city life on the weekends and go to museums, theatres or concerts.

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Register to attend “SciCommConnect: Science communication, community connections”

Posted by , on 16 April 2024

Science communication is an integral part of being a researcher. Want to practice your science writing and presentation skills? Register to attend “SciCommConnect: Science communication, community connections“!

The three community sites supported by The Company of Biologists – the Node, preLights and FocalPlane – are hosting a free, online event on Monday 10 June 2024 from 13:00-18:00 BST, focusing on the different ways in which science can be communicated. We hope this event will present a unique opportunity for you to work on your science writing and presentation skills and connect with your peers across the world in a friendly, informal environment.

Registration closes on Friday 7 June 2024.

Highlights of ‘SciCommConnect’

“Shareable science” by Jamie Gallagher 

Dr Jamie Gallagher is an award-winning science communicator, trainer and consultant. He will share tips and tricks on how to make science talks as interesting, engaging and memorable as possible.

Three minute research talk competition

Similar to the Three minute thesis competition format, this is a chance for you to practice communicating your research in a concise and engaging way.

Present your work for a chance to win a cash prize and to get feedback from Jamie, who is a previous Three Minute Thesis winner. To enter please provide us with short summary of your intended talk (think about how you would advertise your talk in a tweet!)

Applications for the short talk competition are optional and spaces are limited.  Deadline for entering into the competition is Sunday 26 May.

Those who do not wish to give a talk will also benefit from listening to people’s talks and Jamie’s feedback. They will also be able to vote for their favourite talk.

#DevBiolWriteClub and themed writing sprints

Prof John B. Wallingford is a Professor at UT Austin. He is passionate about writing and has written on the Node regularly, including the popular #DevBiolWriteClub posts. He will share some excellent writing advice which can directly be applied during the themed writing sprints that will follow. 

For the writing sprints, you can pick which group to be in (the Node, preLights or FocalPlane). Each group will work together to brainstorm and draft a piece of writing on a pre-selected topic. Details of the writing briefs for each group will be provided closer to the event.

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Embryos in hungry mouse mums postpone development

Posted by , on 15 April 2024

A press release from Development

It’s challenging to sustain a pregnancy when food is short, or conditions are otherwise tough. That’s why many mammalian embryos can postpone their growth to get through periods of environmental stress and then re-enter development when conditions improve. This stalling of development is known as embryonic diapause, and understanding the mechanisms behind it might help improve infertility treatments, such as embryo freezing. Now, researchers at the Center for Excellence in Brain Science and Intelligence Technology, the Chinese Academy of Sciences in Shanghai, China, have discovered how nutrient depletion is sensed by embryos growing in hungry mouse mums to induce diapause. They publish their study in the journal Development on 11 April 2024.

A mouse embryo (blastocyst) that has paused its development due to nutrient depletion. Image credit: Jiajia Ye.

Lack of food is a known trigger of embryonic diapause, but it has not been clear how nutrient depletion in the mother’s diet is sensed by the embryo. “Seasonal starvation is one of the universal environmental stresses in nature,” explained Professor Qiang Sun, who led the study. “However, the regulatory process of diapause in early-stage embryos is not fully understood. So, we decided to examine whether nutrient deprivation induces embryonic diapause.”

By comparing hungry and well-fed pregnant mice, the team discovered that embryos in the hungry mice did not implant into the uterus and their growth paused at an early timepoint, when the embryo comprises a hollow ball of cells called the blastocyst. These embryos remained viable and could start developing again when transplanted into a well-fed mother.

To work out which nutrients were important to induce diapause, the researchers grew early-stage mouse embryos in dishes that contained different nutrients. They found that embryos grown in dishes lacking protein or carbohydrates paused their development, whereas the embryos exposed to normal nutrient levels did not stall and kept on developing. The scientists then went on to reveal that nutrient sensors in the embryo can detect drops in protein or carbohydrate levels, which triggers the entry into diapause.

The finding that embryos grown without protein or carbohydrates can pause their development means that they can survive longer in the lab. In the future, this finding might lead to improvements in fertility treatments, which currently include approaches such as embryo freezing. “We think our study can inspire the development of new methods for human embryo preservation,” said Professor Sun. “Embryo cryopreservation is a widely used approach, but there is still no consensus on when cryopreserved embryos can be thawed and transferred into the uterus. Many clinical studies have shown that traditional frozen embryo transfer can increase the risk of problems during pregnancy. Therefore, it is necessary to develop alternative methods to preserve embryos.”

Studies focusing on diapause may even have long-term implications for cancer treatments. “Dormant cancer cells which persist after chemotherapy resemble the diapaused embryos,” said Professor Sun. “Consequently, we hypothesize that delving into the mechanism of diapause may have positive implications for cancer treatment and decreasing the chances of relapse.”


Jiajia Ye, Yuting Xu, Qi Ren, Lu liu and Qiang Sun (2024). Nutrient deprivation induces mouse embryonic diapause mediated by Gator1 and Tsc2. Development, 151, dev202091 doi: 10.1242/dev.202091

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Categories: Research

Transitions in development

Posted by , on 12 April 2024

Development has just published their 30th interview in the ‘Transitions in development‘ series.

This series of interviews features principal investigators (PIs) within the first five or so years of establishing their own research group. Through these conversations, Development aims to illustrate that there is not a ‘one-size-fits-all’ approach to securing an independent position and setting up a research programme. Discussing the challenges and difficulties new PIs have overcome and highlighting the best moments will hopefully offer encouragement to other ECRs and stimulate discussion around the career path of a developmental biologist.

Click on the pins to read the interviews:

Collage of all 30 interviewees in the ‘Transition in development’ series.
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Categories: Interview

Lab meeting with the Charrier lab

Posted by , on 11 April 2024

Where is the lab?

The lab is located in the southern part of the city of Lyon, France on the campus of the Ecole normale supérieure (ENS). It is one of the CNRS research groups at the Institute of Functional Genomics of Lyon (IGFL), which focuses on integrating developmental, physiological and evolutionary perspectives to study complex biological systems at the organism level.

Research summary

Our group studies the morphogenesis of brown algae. These organisms, some of which can grow to 45 m long, have evolved independently of plants and animals. We work on identifying the strategies that these organisms have adopted to establish their body plans at the embryogenesis stage. In particular, right now we are exploring which mechanisms control the position and the orientation of cell division planes. When, where and how do cells grow and divide is our current obsession!

This question is even more challenging when applied to our favourite models: brown algae are largely understudied multicellular organisms that possess unique cellular components – in terms of cell wall composition, vesicular and cytoskeleton organisation, pigments – resulting from their distinctive evolutionary pathway.

Lab roll call

Marie Zilliox: I’m a post-doc with a PhD in zebrafish development, and my mission is to monitor the growth of brown algal embryos in real time and in 3D using light-sheet and multi-photon microscopy techniques to determine whether cell shape controls the orientation of cell division. The challenge lies in mastering long-term time-lapse microscopy in 3D and in culture conditions compatible with the natural environment as well as with the presence of pigments that diffract light.

Tanguy Dufourt: I’m a first-year PhD student. I hold a Master’s degree in Systematic Evolution and Paleontology (MNHN Paris), and I am now studying which intracellular mechanisms are involved in the orientation of cell divisions in brown algal cells. I aim to model the displacement of centrosomes during the cell cycle by using software based on the forces generated by and applied to dynamic microtubules. First, I need to adapt this software to the cell biology of brown algae: cuboid cell shapes, presence of chloroplasts and vacuoles, throughout the cytoplasm, etc.

Alexis Martel: I have a Master’s in Marine Biology (Toulon University, France), more specifically in biotic interactions and anthropogenic disturbances in marine environments. I work here as a lab manager. In the past 6 months, I have set up most of the lab equipment and the cultures of the brown algal models of the team at IGFL. Now I am developing new microfluidics protocols for the forthcoming team projects involving this technique.

Bernard Billoud: I am a lecturer with a 30-year university career in bio-informatics, and a researcher working on modelling and simulation of algal development. My role is to develop mathematical and mechanical models that can account for the tissue patterning in brown algae. As a member of a team where most of the members are involved in experimental work on the bench, I can assess the time and technicality required to obtain the quantitative data on living organisms that I need to validate the models.

Bénédicte Charrier: I am the leader of the team. As a former land plant biologist, I have been studying the development of brown algae for the past 20 years. I come from a molecular and genetic background, and I am now studying the role of mechanical forces in the process of morphogenesis. Interdisciplinarity combining cell biology with mathematics and physics is what I need to answer my questions.

Favourite technique, and why?

Bénédicte: I love penetrating the microscopic world! Beyond observing live or fixed, labelled or even unlabelled cells, I am now captivated by microinjection. It provides me with an “intimate” moment spent with the algae. Microinjection requires lengthy preparation, but when the time has come for the needle to touch the cell surface, then the conversation starts. And in this specific context, different cells of brown algae reveal their lot of unexpected responses!

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

Bénédicte: I’d like to understand the complexity of biological systems. How do cells co-ordinate themselves or work together to form an organism? How do the different molecules that make up a cell interact to produce a functional living cell? What are their priorities and tolerances (plasticity, robustness)? What are their molecular and chemical bases? What role does self-organisation play? I like to think that the mechanisms of life are based on simple mechanistic rules, perhaps made up of complex interactions at the chemical/molecular level.

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

Bénédicte: I would like to say that I’ve taken part in training courses organised by my employer to help me manage all the tasks I have to do as well as possible, but that’s not the case!  We’re a small team with a large proportion of young scientists in training. The belief that we’re all highly committed and motivated by our work is undoubtedly the cement to building trust among everyone on the team. My favourite time of the week is when I’m fed fresh results, straight from the oven!

What is the best thing about where you work? 

Marie: The mutual support between the people from different research teams at the IGFL and also between the different laboratories and facilities located in Lyon (e.g. the Reproduction and Development of Plants laboratory, the PLATIM Imaging Core Facility) is a real help and relief especially when setting up a new laboratory, which is the case for the Charrier lab, which recently joined IGFL.

Tanguy: A good point of the lab is that the infrastructure is recent and the office is very close to the lab.

Alexis: Our laboratory is affiliated with the ENS, which is a renowned research centre with a vibrant and stimulating environment. The lab itself is recent and bright, so it’s quite pleasant to work in. The different teams work on very varied and interesting subjects.

Bernard: The lab is a very stimulating environment, where people work very seriously in a relaxed and enthusiastic atmosphere.

Bénédicte: The IGFL is an open-minded institute, with a wide variety of model organisms and scientific questions. You would think that this diversity would be unsettling or uncomfortable on a day-to-day basis when it comes to technical difficulties or model-specific issues, but it’s not. Open-mindedness is the DNA of the IGFL! What’s more, the institute is currently broadening its approach to developmental biology and recruiting new teams from different backgrounds. The fact that the IGFL is located on the ENS Lyon campus means that there are plenty of seminars by world-class scientists. The campus is quite cosy, but still offers a wide range of opportunities to develop my project in excellent conditions.

What’s there to do outside of the lab?

Marie: The laboratory is perfectly situated close to the Lyon city centre, where there are plenty of restaurants and bars to suit all tastes, from a cozy café to a night of dancing. Lyon is full of things to do, with an exhibition or concert every weekend. Lyon’s location is also ideal for getting to cities such as Annecy, Marseille, Paris and Geneva in less than 2 hours, which is perfect for weekend getaways.

Tanguy: In Lyon there are a lot of cultural places, like concert halls or museums.

Alexis: Lyon is a very pleasant city. The “Vieux-Lyon”, which is the old quarter in the city centre is a pleasant place to wander around. Also “le Parc de la Tête d’Or” is a peaceful green city park, where I like to go for walks.

Bernard: Lyon has all practical and cultural facilities of a big city, with relaxing natural sites nearby.

Bénédicte: The Alps being less than 2 hours’ drive away is a major advantage when you like to be outdoors, in the mountains. The Mediterranean Sea isn’t that far away either. Lyon is also actively developing its cycling infrastructure, with greenways available in the near future. This is a considerable advantage when, like me, stopping taking the car to work becomes a daily priority.

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SciArt profile: Maja Mielke

Posted by , on 10 April 2024

In this SciArt profile, we meet Maja Mielke, who is doing a PhD in functional morphology and enjoys making nature-inspired drawings.

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

Currently, I’m pursuing a PhD in functional morphology at the University of Antwerp (Belgium), but originally, I’m from Germany. I did my bachelor’s in Molecular Biophysics in Berlin but switched to Biology & Evolution for my master’s because I wanted to study animals rather than molecules. This way, I discovered my fascination for the functional morphology and biomechanics of vertebrates. I studied squirrels for my master’s thesis and switched to birds for my PhD. I’m exploring how they move their beak while processing, cracking, and husking seeds.

Were you always going to be a scientist?

Pretty much, yes. Especially the natural sciences have always sparked my interest and fascination for the world around us. Becoming a scientist was the logical step after finishing school. The hardest part was to choose a field of study! But the interdisciplinary Biophysics bachelor program was the perfect fit at that time.

And what about art – have you always enjoyed it?

I have practiced and enjoyed art a lot during my school years. But once I started my bachelor studies, I was so occupied with lectures, practicals, and exams that there was hardly any room for creating art. Only during my masters did I attempt to re-integrate an art practice into my life. Unfortunately, while managing work, family, and other hobbies, I still haven’t managed to practice art on a regular basis until now. But whenever I finish a piece, it makes me really happy.

What or who are your most important artistic influences?

First, my art is primarily inspired by nature and my fascination for the animal world. That determines my ideas on what to illustrate in the first place. Second, I’m inspired by the work of both professional artists (like Ben Rothery, Alphonso Dunn, Denise Soden, and Raoul Deleo) and fellow hobby artists that share their work online. Studying their art influences my own artistic approaches and inspires me a lot. Third, my art is highly influenced by the work of wildlife photographers, whose beautiful work I use as references for my drawing practice. Last, I’ve been highly influenced by drawing and painting courses that I attended during my life, be it a painting class for children during primary school, more advanced naturalistic drawing classes during high school, or a scientific illustration course I attended two years ago during my PhD.

How do you make your art?

Most of the time, I draw from reference photos. I usually work in pencil or ink, sometimes with watercolor, and very rarely digitally. Because of my limited free time during normal working days, I often finish a drawing during multiple sessions spread over the evenings of several days. If I’m not working on an elaborate piece, I mostly just practice some basic drawing skills with quick sketches in my sketchbook.

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

Sometimes, it’s more the other way around: my science influences my art. I create my own scientific illustrations, e.g., for conference presentations or papers. Also, because I study birds, I particularly enjoy drawing them. But most of the time, my art is doing its own thing, just exploring the animal world and pausing for a sketch whenever inspiration hits.

What are you thinking of working on next?

I would like to further improve my pen and ink drawing skills and explore drawing with dip pens. I love the minimalistic approach of using only black ink as a medium instead of dozens of colors. Visualizing different textures like feathers, fur, and scales with only ink lines or dots is challenging but also so much fun.

Find out more about Maja:

Website: http://www.mielke-bio.info/maja

Mastodon (art):      https://mastodon.art/@majamielke

Mastodon (research & science communication): https://scicomm.xyz/@MajaMielke

ResearchGate: https://www.researchgate.net/profile/Maja-Mielke

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Categories: Science Art

Royal Society Meeting on Cell Lineages

Posted by , on 9 April 2024

Birmingham, UK, May 7-8, 2024

Edgbaston Park Hotel and Conference Centre

There’s something for everyone, whether you’re into classic lineage tracing/fate mapping, imaging-based cell tracking, genomic barcoding, or somatic mutation tracing. Come interact with experts on these techniques, covering development, regeneration, and disease, in classical and non-classical model organisms.

Registration is free – just go to the website and request an invitation:

https://royalsociety.org/science-events-and-lectures/scientific/request-an-invitation/

We very much welcome abstracts for both oral and poster presentations – send your abstract here:

scientific.meetings@royalsociety.org

Registration and abstract submission close this Sunday April 14, so don’t miss out!

We look forward to having you with us!

Details:
https://royalsociety.org/science-events-and-lectures/2024/05/cell-lineages/

Confirmed speakers:

Simon Hippenmeyer – IST, Austria
Ben Simons – Cambridge University, UK
Shosei Yoshida – NIBB Okazaki, Japan
Elizabeth Murchison – Cambridge University, UK
Sarah Bowling – Boston Children’s Hospital -USA
Bushra Raj – UPenn – USA
Elke Ober- FAU Erlangen Nurnberg, Germany
Trevor Graham – ICR London, UK
Patrick Lemaire – CRBM, Montpellier – France
Colinda Scheele – IB-KU Leuven, Belgium
Michael Ratz – Karolinska Institute, Sweden
Michel Cayouette – IRCM Montreal, Canada
Periklis Pantazis – Imperial College London, UK
Ana Cvejic – University of Copenhagen/BRIC – Denmark
Marketa Kaucka – MPRGL MPI – Germany
Mekayla Storer – Cambridge Stem Cell Institute, UK

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Categories: Events