Hello, I am Margot Smit, a new PI and a new contributor to the ‘New PI Diaries’ from the Node. On October 2nd (today) I am starting my lab at the Center for Plant Molecular Biology in Tübingen, Germany. In my lab we will study how the timing of cell fate progression is controlled in plan development. We will start out studying stomatal and vascular development during Arabidopsis embryogenesis, where I previously identified blocked fate progression. For more check out my website (lab website at ZMBP under construction).
The first few months of this new job will surely be exciting and overwhelming. Apart from having a new job description, I’ll be in a new institute with different habits and rules, and many unknowns. My first challenge will be getting to know the place and its quirks, something that I’ve learned never to underestimate. I’ve done Arabidopsis research at 3 different universities so far (Wageningen University, UC Davis and most recently Stanford) and I’ve found it’s best not to make too many assumptions. Because while they had enthusiastic, welcoming colleagues and excellent facilities in common, every place had its unique ways of organizing things. From reagent ordering to microscope booking, to meeting structure, to my favorite topic: fertilizer. I love talking about moving labs and finding plant fertilizer.
Fertilizer is the topic I go to when I explain what it’s like to move to a different institute. Since I have some experience doing Arabidopsis research, I used to assume that meant I didn’t have to ask a lot of questions when starting somewhere new. Some things are always the same. Arabidopsis needs nutrients and so we add plant fertilizer to the soil. At Wageningen we ordered trays of prepared soil from central facilities, they would arrive the next week, ready to go in whatever pots we requested. Then I moved to Stanford and the lab manager showed me around, showing me where the soil (and fertilizer pellets) for making trays were. I didn’t realize I needed someone to show me this, but it has turned into a fun experience. That lab manager is unfortunately no longer in the lab and several new lab members joined who had previous experience growing Arabidopsis so they didn’t think to ask about our soil. Then 2-3 months later they would wonder why their plants were not doing so great. And then they learn that there is no fertilizer in the soil or in the water (as was the case at UC Davis) but that they need to add it separately. While this was probably frustrating, there are worse things — like growing your non-Arabidopsis plants for many months and wondering why they do so poorly… This is what happened to a friend who moved from UC Davis to another UC where there was no fertilizer in the water. A lot more lost time and frustration than 2-3 months.
There is so much that is the same between institutes and so much that is different. One challenge is not knowing all the differences from the start. So as I get ready to start in a new place I am preparing to learn all the obvious differences but also to find the unexpected ones. I’m sure there’s many things I’ll miss and do wrong initially, but I am looking forward to learning and I hope people will be (somewhat) forgiving. Luckily, an experienced technician will join my lab which I’m sure will make finding the fertilizer (and starting a lab) a lot easier. In the first month I’ll be getting to know the institute, setting up materials, interviewing for a big grant, and hiring my first PhD student. Wish me luck!
[Update Oct 2nd: Fertilizer is already mixed into the soil here it seems. Interesting]
The Kerosuo lab, The Neural Crest Development and Disease Unit, is part of the National Institutes of Health Intramural Research Program at the National Institute of Dental and Craniofacial Research, and it’s located in Bethesda, Maryland, USA
The overall aim of the Kerosuo Lab is to provide a comprehensive picture of early neural crest development as part of the ectoderm patterning process and neurulation, and to use this knowledge to unravel the pathology behind neural crest derived diseases known as neurocristopathies. We focus on understanding the molecular mechanisms behind neural crest pluripotency-like stem cell maintenance, how fate choices are made, the extent of heterogeneity and plasticity in neural crest potential, and whether our findings on normal developmental processes apply to neural crest-derived birth defects and cancer. To answer our research questions, we use a combination of biochemical, cell, and molecular biology techniques and single cell and live imaging on chick and mouse embryos as well as on human ES-cell-derived neural crest cells. By combining the iPSC-technology to our research, the goal is to create a bridge between normal development and disease and create neural crest cells from patients with neurocristopathies to characterize the underlying cause by using a broad array of modern cell and molecular biology assays, which in part, are further validated by using the in vivo animal models.
Lab group photo
Lab roll call
Karla Barbosa Sabanero is a senior postdoc in the lab who works to understand the mechanisms that maintain the pluripotent state and the cell identity of the neural crest cells.
Jenaid Rees is a new postdoc in the lab uses chick embryology to explore the specific function of genes essential for neural crest specification and survival.
Ed Taroc is a new postdoc in the lab who studies how DiGeorge Syndrome affects the neural crest.
Ceren Pajanoja is a senior PhD student (in partnership with The University of Helsinki, Finland) who studies how the neural crest obtains its exceptionally high, pluripotency-like stem cell potential in the chick embryo, and how different cellular functions and fate determining gene regulatory networks mature and interact with each other during ectoderm patterning.
Jenny Hsin is a MD/PhD student (in partnership with The University of Cambridge, UK) attempting to understand the mechanisms by which neuroblastoma, a pediatric cancer, initiates during neural crest development.
Jamiya Kirkland is a second-year postbac fellow in the lab who works on understanding molecular mechanisms that drive neuroblastoma formation.
Sravya Pailla is a second year postbac fellow who studies pluripotency-related cellular functions in the human neural crest.
Shaun Abrams is an Independent Research Scholar in the lab, whose team studies how the ubiquitin pathway regulates neural crest development and how centrioles/cilia coordinate craniofacial development.
Favourite technique, and why?
Laura: I like multiple techniques and will never get tired of admiring beautiful high-resolution images. The self-developed single cell Multiplex Spatial Transcriptomics technique (scMST) we use in the lab is impressive; every 3D image showing the pseudo-colored cells forming transcriptionally distinct subpopulations in the original spatial location in the tissue makes you humble and grateful for the fact that we can see into the embryo in such detail. I also enjoy how we can now model human neural crest development in organoid cultures and finally learn about the human details as we never get access to the young enough human embryos to study this. However, at the end of the day, my favorite technique probably is and will always be the gastrula stage gene perturbation technique in the chicken embryo to address developmental mechanisms at neurula stage; it is so satisfying to see an effect of your manipulation on one side of a real embryo, and directly compare the result to the contralateral control side. No matter what your hypothesis is, the embryo will tell us the correct answer.
Apart from your own research, what are you most excited about in developmental and stem cell biology?
Laura: I am fascinated by the recent progress in the assisted and self-assembling organoid field not to mention the incredible success of making entire embryos on a dish from cultured pluripotent cells!
How do you approach managing your group and all the different tasks required in your job?
Laura: I don’t think anybody can ever be perfect at this as it always feels like there is too much to do. I try my best by being quite well organized, I keep adding tasks to a long “to do” list, and I also categorize them by deadlines in my notes. Unfortunately, only twice during my PI-career have I had the rewarding feeling of finishing the list! In addition to labmeeting and spontaneous need-based meetings, I have standing weekly meetings with everyone in my lab, which provides a good structural basis so that I don’t lose track. As a mother of three children, I have been forced to a disciplined lifestyle for a long time already, which in this respect has served as an advantage.
What is the best thing about where you work?
Laura: The multidisciplined, enthusiastic, and collegial research environment and the elaborate funding resources of the NIH. As a PI, it’s a privilege to be able to solely focus on the research without any teaching or grant writing responsibility.
Jenaid: The NIH has both amazing resources and incredible opportunities for collaboration.
Ed: The best thing about working for the NIH is that it is the NIH, one of the top research institutes in the country (maybe the world?), the amount of resources available to me feels amazing.
Jenny: The NIH is an amazing place for collaboration and resources – there are so many people and cores willing to answer your questions and offer their expertise.
Shaun: NIDCR is a very collegial and collaborative institute, the resources and core support are amazing, and the people who work here are very supportive in helping to troubleshoot experiments and brainstorm innovative new scientific questions/ideas.
Karla: I enjoy that the NIH has a vibrant diverse community with a collaborative environment.
What’s there to do outside of the lab?
Jenaid: There are beautiful hikes and vineyards a short drive away- it’s a lovely way to spend the weekend.
Ed: I’m new to the DC/Maryland area but outside of lab in general I like to go running, hiking (I’m from upstate NY so literally a pass time for a lot of us), reading books, and also playing video games. I’m also really into exploring the area to find good places to eat and get good drinks, and you can usually find me roaming around the city with friends having a good time.
Jenny: The DMV area has so many things to do – DC has tons of free museums and an amazing food scene with plenty of restaurants and bars to check out. I also love being outdoors – the Rock Creek and Capital Crescent Trails are my favorites to go running on.
Shaun: There is so much to do in the DMV area. From great restaurants, hiking trails, museums, and concerts, I am never at a loss for things to do here when I’m not in lab.
Karla: This region has beautiful parks and green areas where you can enjoy hiking, rowing, and biking. Also, being so close to DC there are lots of events and fun for all.
Browse through other ‘Lab meeting’ posts featuring developmental and stem cell biology labs around the world.
The Beddington Medal is awarded by the British Society for Developmental Biology for the best PhD thesis in developmental biology, defended in the year prior to the award. The medal is named in memory of Rosa Beddington, who made major contributions to both the field of developmental biology and the BSDB. The artwork on the medal is from Rosa’s own drawings.
The 2023 Beddington Medal is awarded to Rasa Elmentaite. Rasa completed her PhD in SarahTeichmann’s lab at the Wellcome Trust Sanger Institute. We caught up with Rasa over a cup of coffee in Cambridge to learn more about her background, her PhD work on the Gut Cell Atlas, and her future plans.
First of all, congratulations on receiving the 2023 Beddington medal! What does that this award mean to you?
It’s an amazing recognition, as developmental biology is a huge part of my PhD and the part that I most enjoyed thinking about. I find it incredible how studying developmental biology can help to not only understand how normal tissues form, but with the emergence of cell therapies, inform development of new disease treatments too. The award also means a lot to me personally, because I come from a small city, and I don’t have any scientists in the family. It means a lot when my family, my uncles and aunts messaged me saying, “wow you’re recognized!”
Rasa Elmentaite
You mentioned coming from a small city, so let’s go back to the beginning. Where did you grow up?
I am from Lithuania. It’s a small, but culturally rich country with 3 million people. I grew up in a single parent household — it’s just me, my sister and my mom. My interest in sciences started when I followed my sister’s footsteps and got into one of the best schools in my city that is STEM oriented. My biology teacher was strict but also very engaging and she would always make sure we were the best of the best in biology and medical sciences. Perhaps that is the reason why half of my classmates became medics or scientists. My family also believes that in order to achieve something in life, one has to study very hard. Early on I followed this religiously.
How did you come to do a PhD at the Wellcome Trust Sanger Institute with Sarah Teichmann?
After school, I decided to go abroad and pursue an undergraduate degree at the University of Glasgow. This was a big deal for me, because I was the first one in my family to leave the country and study abroad. During my time in Glasgow, I sought out various internships during the summer holidays to gain hands on experience working in the lab. I worked in a neuroscience lab on pathways of pain and itch and later on I used Drosophila as a model system to study stem cells in the fly gut. Most of my lab experiences until that point had been on hypothesis-driven science. When I was applying for a PhD, I was intrigued by the Sanger Institute’s PhD programme. The institute uses an approach to science that I never experienced before — they generate a lot of data in order to form new and exciting hypotheses. I went from doing experiments in the lab and not knowing how to analyse data at all, to doing a PhD in a bioinformatics Institute. It felt like learning a different language.
In my first year at the Sanger PhD programme, I did three rotations. One of them was with Sarah Teichmann and Ludovic Vallier, who is an expert in stem cell biology and iPSC-derived cultures. My project involved doing single cell analysis together with Sarah Teichmann and her team on iPSC-derived gut organoids. I tried my best to make sense of the data that I generated during my rotation. By the end of my rotation, I still struggled to interpret cell type identities of these organoids, partly because there was no reference of what the normal gut cells look like. That’s how my PhD project came about. I decided to join Sarah Teichmann and the international Human Cell Atlas initiative that Sarah co-founded to create comprehensive maps of all the cells in the human body. My goal was to map the cells of the human gut and understand how their identities and organisation in tissues change from development to adulthood, and in diseases.
Rasa is part of a diverse team of scientists from across the world at the Sarah Teichmann’ laboratory and Wellcome Sanger Institute. Rasa is middle row, sixth from the left.
A large part of your PhD involved putting together the Gut Cell Atlas, which was published as a paper in 2021. Can you talk more about the work involved?
The idea of this project was to map single cells from different regions of the human gut at different timepoints from early development to adulthood. We didn’t have a specific hypothesis, but we wanted,amongst other questions, to know more about immunity in early life. We also wanted to map the gut in a comprehensive way so that the gut segments we collect reflect the regions where inflammatory diseases manifest.
A crucial part of the project was tissue access. We were very fortunate at the Sanger Institute to have access to organ donor tissues from Cambridge Biorepository for Translational medicine and foetal tissues from Human Developmental Biology Resource in Newcastle. We were also able to get samples from healthy children and children with inflammatory bowel disease through collaboration with Matthias Zilbauer in Cambridge. Some of these tissues came late at night, the surgeons were dedicated to retrieve them and provide them for research, which was critical for my PhD. I am very grateful for these efforts.
But it wasn’t just me — I was part of a large team. There were a lot of people involved, and without them, that project wouldn’t have happened. I had a lot of support from teams at Wellcome Sanger Institute who manage human tissue ethics and access, sample sequencing and colleagues in Teichmann, Zilbauer, Haniffa labs who helped with the protocol development, experimental design and data analysis. My PhD was truly a very unique experience that involved a lot of teamwork.
While this was exciting time in my PhD, it was also unusual at times. For example, I had to leave Cambridge for weeks and live in a hotel room in Newcastle in order to collect the samples on time ensuring that we generate good quality data. Logistics was difficult. I learnt that I much prefer the data analysis aspect of my project, because it involves asking scientific questions and with bioinformatics work it sometimes feels like the answers are at your fingertips.
Rasa uses hight throughput single cell (left) and spatial (right) genomics methods and computational tools to resolve the identity and features of lymphoid tissue initiator cells (LTi) as well as their contribution to gut-associated lymphoid tissue formation in humans. The atlas data is available at https://www.gutcellatlas.org/
Do you have a favourite piece of data/ insight from the Gut Cell Atlas?
My favourite discovery relates to the formation of lymphoid tissues during human development. This intricate process involves three key cell types involved: lymphoid tissue initiator cells and two types of lymphoid tissue organiser cells. Understanding their interactions in developing human tissues is crucial for recruiting and retaining immune cells in lymph nodes and gut-associated lymphoid tissues – a process that is critical for development of normal immunity.
I recognised these cells in our atlas, because they have been characterised and studied previously in mouse models. Even still when I saw these cells in our Atlas, it felt like an accident because they are so rare in tissues. Even more exciting was that the organizer cells transcriptionally shared characteristics with the fibroblast cells we mapped in Crohn’s disease. I remember telling Sarah and our collaborator and immune development expert Muzz Haniffa about how these developmental programs could be working in disease to recruit immune cells during inflammation — maybe there is a way we can better understand disease through our developmental atlases. Then Muzz said, “I’m looking at exactly the same thing in psoriasis!” and I knew this is a discovery that is worth pursuing and understanding further.
Rasa’s work on mapping the cells of the human developing gut contributed to better understanding of cellular and molecular mechanisms during enteric nervous system development and epithelial crypt-villus formation early in life. Fluorescent images show colonisation of the myenteric plexus by enteric neural progenitors (left) and emergence of intestinal stem cells (green, LGR5) in the human fetal intestine (right).
The Gut Cell Atlas work is part of a larger initiative called the Human Cell Atlas. What was it like being part of the initiative?
Within the consortium, every scientist brings their own expertise, from clinicians to biologists and data scientists. It feels like we’re all pieces of a puzzle and we come together to solve this complex problem of mapping cells. We share one goal — create a reference that can help future scientists to answer their own research questions. I think that’s something I’ll be very proud of in the future, and I already am, especially when other researchers tell me that they’ve used the Gut Cell Atlas and the data has helped them to answer their own scientific questions. Being part of the consortium also provides connection to other researchers who are working on similar questions. It generates a lot of enthusiasm, inspiration and provides a lot of support. It made me feel that even though we have a huge task in front of us, it is achievable if we work together.
Rasa is part of an international Human Cell Atlas consortium. The picture shows participants at the HCA general meeting in Toronto, Canada 2023.
Did you work on other projects during your PhD?
The culture at the Sanger Institute and the Teichmann laboratory is extremely collaborative. I was involved in multiple projects with members of Teichmann group, other groups at the Sanger Institute and also external collaborators. For most projects, I used my experience analysing single cell data to answer new and intriguing questions. For example, I worked on a project with collaborators in Oxford led by Holm Uhlig that aim to better understand how cells in the gut contribute to monogenic Inflammatory Bowel Disease. Another project focused on characterising enteroendocrine cell in an organoid system together with a team from Hans Clever’s laboratory. Even though the project only involved online interactions, it was a nice topic for me to work on because it brought me back to early days of my PhD, when I was trying to better understand organoid cells. It was much less frustrating this time round because now we had a reference to compare these organoid cells to!
There were also collaborations that were much less expected, like a project on Schwann cells. The gut has Schwann cells that migrate and colonize the gut during development and contribute to establishment of the enteric nervous system- so called second brain. A paediatric scientist, Sam Behjati, who is passionate about understanding childhood cancers was looking at the origins of neuroblastomas. We were interested in whether neuroblastoma cancers share similarities with some of the Schwann cells that we captured by profiling developing gut and adrenal glands. It was a very special project not only because of the translation impact of the project, but also because the lead author is a fellow Lithuanian Gerda Kildisiute and we had a great time working together.
Were there any frustrating moments during your PhD?
The one obvious frustration was the pandemic, which of course, affected everyone. There were already many challenges with the process of getting tissue access because the human samples are rare. When the pandemic hit, we couldn’t do any more experiments because the Institute’s focus, for good reason, shifted to better characterising and tracking the virus. The silver lining for me was that I could stay back home and focus on bioinformatic analysis of the vast amount of data that we generated. Nevertheless, during this time I missed the in-person interactions with members of our group. I feel these interactions and discussions were key for advancing scientific ideas during my PhD.
If you took one abiding memory with you from your PhD, what would it be?
There are a lot of joyful memories from my PhD, and it is challenging to pick one. I have great memories marking the day we learnt that our paper was accepted in Nature. I shared this moment with my colleague and mentor Kylie James and Sarah in her garden. It felt surreal. It was great to know that our data and insights into developmental and disease biology will have a broad reach. Personally, it also felt like a huge achievement and it was enabled by my supervisor’s willingness to give me independence, support and a feeling of trust that made me believe in myself. I think this is a key quality in a leader and something I aspire to carry over when I eventually have my own team.
Speaking of good supervisors, what do you think about the importance of having good mentors and supportive people around you?
Having female mentors and role models means a lot to me, and it extends beyond my PhD supervisor, to all my previous colleagues and mentors. I could relate so much more to them and it meant a lot to see that they are incredibly passionate at work and also have busy lives outside work. The achievements on my CV were only possible because the female leaders I had a chance to interact with. Starting with Sarah who has given me countless opportunities to present at the conferences, meet people in and outside academia and form unexpected collaborations. The lab members around me have also been very supportive and the supportive culture is propelled by the fact that everyone has their own experiences and expertise. We come together to interact and learn from each other. It’s never competitive.
What have you been working on since you completed your PhD? What’s next for you?
After my PhD, I sat down with Sarah to discuss what I could do next. I remember thinking I didn’t even know where to start looking for opportunities— should I stay in academia, transition to industry or try the start-up world? The opportunity came to co-found a start-up company together with Sarah as well as colleagues at Sanger Institute with expertise in the cell engineering field. I thought, it is now or never!
I decided to give myself one year to get the start-up going, which looking back was quite ambitious. During that year I worked as a staff scientist and dedicated my time to think about translational applications of the Human Cell Atlas data and computational tools that have been developed in the group. We started raising money on the idea of identifying drug targets using Human Cell Atlas data. The aim is to create a platform to better understand cellular and molecular mechanisms of disease and identify potential off-target toxicities through the Human Cell Atlas data. At the same time I also completed an internship with Foresite Capital, which gave me a unique perspective into the world of Venture Capital. These experiences and interactions exposed me to a different career path and greatly shaped my ideas on how to generate impact from the Human Cell Atlas research.
Longer term, do you know if you plan to stay in science?
I am a scientist at heart, and I think I’ll always stay in science in one way or another. For me it doesn’t really matter if I stay working in academia or pursue science in other ways. As long as I’m staying curious and creative about how I ask questions and interrogate the data in front of me, I consider myself a scientist.
Where do you think developmental biology will be in ten years? How do you think single-cell and spatial transcriptomics methods will advance in the next decade?
Single cell transcriptomics methods are increasing in resolution and becoming cheaper too. I am excited to see the day when we will be able to measure all the facets of a cell, including DNA, RNA, protein from a single cell as well as its spatial location in high throughput. Connecting this with gene and cell perturbations is going to be another step to better understand how cell identity is determined. It’ll be exciting to see how the data we generate will be combined with generative modeling and foundational AI. I am curious to see how this will improve the way the data is interpreted and what kind of insights we can get from it. I’m also excited about the developments in in vitro models and the way the field is advancing. There’s a lot of potential for understanding early human development through the lens of in vitro modelling and single cell genomics.
Outside of the lab, what do you like to do?
I enjoy trying new activities and generally staying active. Most weeks I enjoy bouldering, working out at the gym and I have also recently started cycling and running. On the days when I don’t want to be active, I design knitting projects – it is a hobby that I started during lockdown. Some people think it is an old-fashioned hobby, but for me it is an incredibly creative and rewarding activity because I get to make something entirely from scratch.
The FocalPlane Network is an international directory of researchers with expertise in microscopy. It is designed to promote networking, as well as a resource for those looking for collaborators, reviewers, speakers and committee members.
Like the Node Network, the FocalPlane Network is an inclusive site and we hope that it will help promote diversity in the microscopy community. Members provide information on their scientific field, microscopy area of expertise, place of work and career stage. They can also voluntarily provide details on aspects of diversity such as gender, race/ethnicity, LGBTQ+ identity and disability status.
You can find out why our members think that the Network is important on a new post FocalPlane. If you use microscopy as part of your research, we would like to encourage you to join and use the FocalPlane Network.
To showcase the variety of interests and artistic talents among the developmental biology community, the Node and the British Society for Developmental Biology (BSDB) is jointly hosting a virtual art exhibition, to accompany the European Developmental Biology Congress(EDBC).
Voting is now open to the public to pick their favourite artwork from the three categories:
1) Scientific images
2) Science-inspired art
3) Art by scientists
There will be a ‘People’s Choice’ from each category. A panel of judges will also pick a winner from each category, who will receive a laser-cut wooden coaster designed by Helen Weavers.
Voting closed on 25 October 2023 23:59 GMT.
Visit the different rooms of the exhibition
The ‘Science-inspired art’ and ‘Art by scientists’ room
Dr. Alexa Sadier is a Research Scientist in Karen Sears’ lab at UCLA. She is using bats as a model system to understand the origin and diversification of a key mammalian innovation, the tooth classes (e.g. incisors, canine, premolars and molars). From the µCT scans and two-photon microscope in the lab to the jungles and caves of Trinidad, find out more about the story behind the team’s recent paper!
What brought you to join Karen’s lab? I joined Karen Sears’ lab in 2015 to study the evolution of sensory systems in noctilionoid bats, the family I am focusing in. As an evolutionary developmental biologist, I quickly fell in love with both the animals and the system.
How did the project get started? What was known about the origin of mammalian teeth before your work? I did my PhD on molar evolution in mice, in which we demonstrated that the particular shape of the mouse first molar can be explain by the complex evolution of dental patterning in this species. This training gave me a deep knowledge of tooth development and the potential of this system. After working on bat vision evolution, I decided to launch my own area of research in Karen Sears lab (I thank her SO MUCH for giving me this opportunity) because I realized that bat teeth are so diverse that they can be a good model system to study phenotypic diversification given our deep knowledge of tooth development in mice. On the contrary to mice, bats possess all tooth classes so we can study not only molars and very derived incisors, but all of them. We can investigate mechanisms that are still not known such as what makes an incisor an incisor, a canine a canine, a molar a molar, etc. Indeed, most of the developmental studies have been done in mice. We know that tooth class identity seems to be determined early during development, through a prepatterning of the jaw, but our understanding of what happens after and their respective morphogenesis is extremely limited.
What made you choose noctilionoid bats as your model organism? For an evolutionary biologist, noctilionoid bats are a fantastic model since phyllostomids (a group of noctilionoids) underwent an adaptive radiation (like Darwin finches) and have evolved various diets. You probably know the vampire bats which eat blood but other species specialize on fruit, nectar, insects, vertebrates, fishes or even pollen. This adaptation to various diets had shaped their evolution at all levels: the shapes of their skull and teeth are adapted to their main diet, so are other systems such as vision, echolocation, etc. In the Sears’ lab, I realized that what I thought was only possible in model species, such as mice, was also doable in bats (up to a certain point). Before working with them, I would have been skeptical about the ability to perform developmental biology or even functional experiments on non-model species. Now that the genomes are available through Bat1K, and developmental material thanks to field expedition and museum specimens, we have all the tools we need to study them from genotype to phenotype. It’s a kind of an eco-evo-devo researchers’ dream.
Can you summarise your key findings? Noctilionoid bats exhibit a huge variation in their tooth number, size and shape due to the colonization of various dietary niches in only 25 million years, making them a fantastic model to study the developmental basis of rapid morphological evolution. We used integrative approaches (morphological measurement on adults and embryos, cell proliferation labeling and modeling) to investigate the development and evolution of two tooth classes, premolars and molars.
We found that premolars and molars develop and evolve independently by two different Turing-like rules in bats, and probably other mammals, that deviate from previous models (the Inhibitory Cascade (IC) model). This important result brings new insights regarding the developmental and evolutionary differences between tooth classes – a major mammalian innovation – that remain relatively obscure and limited in their taxonomic scope. Then, by linking this variation with the variation in jaw length, we show that the interaction between Turing-like mechanisms and growth rate is sufficient to generate the observed variation. Our work demonstrates how new morphologies are reached by modulating the interaction between multiple developmental constraints during the burst of diversity that accompanies adaptive radiations. While the idea that growth rate variation is important for Turing mechanisms is not novel, our work proposes that it can facilitated the apparition of new phenotypes in teeth and potentially other ectodermal appendages that develop like teeth.
How was it like working with bats? Any memorable stories about the fieldwork? It’s probably my favorite moment of the year even if it implies being sleep deprived, long nights, a lot of work and administrative tasks but all of this disappear when we hold a bat with its little personality. Typically, we travel to Trinidad, Dominican Republic or Puerto Rico for 2 to 3 weeks at the time. Our days and nights are organized around bats. At 2-3 pm, we generally drive to a field site to be ready with our traps at 5-6pm when the bats come out. We then catch them until 11pm and put up a triage station to decide which one we release (95% of them) before driving back with them in cotton bags. Then, the long processing night starts, sometimes often until 5-6 am. We then sleep for a few hours, eat, and repeat. Some people think we go to the beach and enjoy the Caribbean life with rum every night but the reality is that we barely have time to complete our tasks. And when we do, we try to catch some sleep. As though as it could be for the body, there is something magical when we go down into a cave with all the bats flying around us. Forests are also special places, with so many species, so are abandoned houses, sometime frozen in time. I have so many fieldwork memories, but one is particularly fun. When looking for fishing bats, we had, one day, to swim into a bat cave from a boat with our butterfly nets. As we were swimming into the cave, which was like a narrow tunnel, we started to smell them. Then the cave became wider and all the bats were there, with pup, looking at us. We couldn’t believe it was true. Finally, the best of all is probably sharing this with our local collaborators, year after year, triaging bats sitting in the back of the truck, laughing, sharing, nerding, eating the delicious Trinidad doubles, working hard but in such a special atmosphere.
Do you think that doing fieldwork change the way you perform your research? Yes! In eco-evo-devo, it’s a new way to think about the species you work on. Seeing them in their environments can really make a difference in your research. I remember this conversation with a researcher who solely study the genomic aspects of bat evolution. From his dataset, he thought that one bat species was blind although it’s clear, when seen it in the field looking at you, following your finger, looking around, that it is not the case. Fieldwork adds another dimension to our work as evolutionary biologists. From a more personal point of view, as an outdoor person who grew up in the French Alps, I have always been skiing, climbing, hiking, etc. I love being outside and I always think of science as a way to explore, exactly like explorers who discover new territories. Fieldwork represents the ultimate fusion between geographical and intellectual exploration: we are looking for new species, new specimens, new results while we explore new areas and make link between everything.
How was your experience collaborating with people with different expertise for the paper? It was really great, especially regarding the modeling aspect of it. Being able to find a mathematician interested in biology and vice versa was really one of these fun moments in research. Interdisciplinary research is not always easy and it’s always a special moment when everything is finally getting together. It’s also a way to push the boundaries when it works well like this.
Did you have any particular result or eureka moment that has stuck with you? Yes! And it was so good. I was segmenting teeth at the computer and my colleague and friend Neal, who is a co-author, was in the lab. I realized that, in some bats, the premolar that disappears is the middle one (on the contrary to molars) and that it happens gradually during evolution. I was like WTF! and asked him to come next to me to tell him what was his conclusion (without telling him first). We looked at each other being like: that’s AMAZING! It really changed the study and the way I then thought about these results.
And the flipside: were there any moments of frustration or despair? Of course, when the two-photon images were too big (1.6 Tb) to be opened and we had to start imaging everything again not knowing if the dyes would have survived in our precious samples. Or during COVID, when fieldwork was not possible despite our need to get more developmental stages or more museum specimens and thought it would delay the paper. And more than anything else, being a postdoc and then a research scientist with all the uncertainty that comes with it. While it’s exhilarating in so many ways, it’s still a temporary situation that implies a lot of sacrifices, long distance relationships, and living on grants, sometimes not knowing if everything will stop after 6 months. Delaying results can have devastating consequences on an application cycle. I knew I couldn’t abandon this project because I deeply believed in it (its significance, the science behind it and where we can go from it), but I had some close calls because I was so sick of sacrificing many things I love (including my personal life) for my career. I made these sacrifices but not anyone can do it (or even want). For me, this is the most challenging part of developing new risky research at this career stage.
Where will this story take the lab? This paper really showed the potential of this model to study the origin of tooth classes and is the foundation of my future research program. Next research will investigate how the variation of the dental gene network drives tooth class diversification. We will still use bats as a model system and plan to extend to other mammals, and long term, ectodermal appendages that develop the same way!
What is next for you personally after this paper? Hopefully, the best is yet to come! I’m about to start my group using this model system to study the evolution of tooth classes, so this paper constitutes the foundation of the future, it’s a beginning. Developing this model and program (along with the other paper that came out of it) helped me to gain confidence in my science and research and establish my area of research. It will always have a special place.
Reference Sadier, A., Anthwal, N., Krause, A.L. et al. Bat teeth illuminate the diversification of mammalian tooth classes. Nat Commun14, 4687 (2023). https://doi.org/10.1038/s41467-023-40158-4
Pictures: Alexa Sadier, group picture: Marie Treibert
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