During September we ran a writing challenge, giving contributors to the Node a chance to win £200 for publishing a blog post on our website. We really appreciate the effort that all of our contributors put into sharing posts on the site, and we hoped that the challenge would help motivate and encourage writers to share their ideas. The Node is a community for all, regardless of experience, background, skills or career stage. For this reason, we decided to award the prize by randomly selecting the winner rather than a competitive format. We hope this approach reassured authors to share on the Node without apprehension that their work would be judged.
The Node, as well as our other community sites, preLights and FocalPlane, give you a place to share your writing and provide a network that supports you through the writing process. With this in mind, please reach out to any of our Community Managers if you would like to discuss any ideas or drafts for the sites, or if you would like to join the preLights community team. In addition to written posts, the Node welcomes other types of audio or visual communication, including images, illustrations and videos. With challenges such as this one, we also want to remind our readers and authors that anyone can write and publish a blog, and you don’t need an invitation to do so.
The winner of our writing challenge was Umaymah Ahmad with the post ‘It’s about who you know, not what you know. Uh Oh.’. This entry explores how personal connections are crucial in academia and discusses overcoming impostor syndrome in professional environments. Check out our interview with Umaymah:
Tell us about yourself: I am currently in my final year of studying medicinal chemistry. Throughout my studies, I enjoy researching and learning about new topics, and ultimately writing about them. I’ve always had a passion for writing, whether it’s writing a simple opinion piece to entering the odd essay competition. Understanding why things work the way they do has always come to me through writing about and visualising concepts. I enjoy being able to translate theories and ideas into words, to make better sense of the world around me. I also enjoy playing logic puzzles and word games, including the occasional Sudoku, and I hope to never make the grave mistake of missing a Wordle.
Can you describe your research journey? Throughout my studies, my first two years involved developing practical skills and getting an insight into what it is like in research. As part of my BSc project in my third year, I am currently researching MOF’s (Metal Organic Frameworks), which are made using repeating ligands and singular or clusters of metal ions. These structures have pores that can be used in a multitude of ways, specifically in improving efficacy and enhancing drug delivery. With a potential to be modified post-synthesis, they have been applied in the biomedicine field, in bioimaging and sensing.
What inspired you to write this story? I mainly just wanted anyone who feels as if they are ‘out of place’ or an ‘impostor’ to know they are not alone in that feeling, and it is just a feeling, not a reality. I have felt that countless times. Occasionally, it feels like you know a little about A LOT, and every step forward you take makes you feel further behind, but everyone else is also at the same stage, and has felt that before. Having that reassurance can help you escape that spiral, and I hope the story I wrote will reassure everybody, whatever stage of their career or studies they may be at.
Do you have any advice on writing a post for the Node community? What helps me to write is initially having a draft that to someone else, can seem like a whole different language. Noting down every point you would like to discuss, whether it be through a list of acronyms or abbreviations, or a collection of jargon that has meaning to you/your research. Whatever makes sense to you, write everything you want to say down, no matter how incoherent or grammatically incorrect it may be. Opening a new blank document and sifting through the unfiltered draft helps you better pick out key points and can help you build a rough guide as to what points require more or less detail, and ultimately, the direction your article takes.
Have you done any other writing before this post? My experience stems mainly from writing articles for a newsletter at my university. I mainly wrote opinion pieces that raised awareness to a range of humanitarian causes. I also wrote opinion pieces linking to the theme of the monthly issue, which really helped me convey across my thoughts and allow others to look through a different lens. I hope to continue my writing journey by publishing articles, and opinion pieces on platforms such as the Node, where I can further develop as a writer.
I never imagined that tiny fruit flies could reveal so much about the brain and its functions until I spent my summer in Alex Gould’s laboratory at the Francis Crick Institute, UK, under the supervision of Victor Girard. During these two months of internship, I used Drosophilamelanogaster as a model system to investigate the role of circulating lipids in brain development.
As a second-year undergraduate student, my internship at the Crick was an eye-opening experience. It gave me the chance to engage with talented researchers, become a part of a welcoming scientific co mmunity and gain first-hand insight into how research unfolds in the real world. The Gould lab focuses on understanding how the developing central nervous system (CNS) adapts to environmental challenges such as hypoxia and nutrient deprivation. This research direction resonated with my own interests in neurobiology, making the experience both relevant and inspiring.
Lipids are essential for the structural framework of cells. They are, however, not just the building blocks of cell membranes but are also vital for energy storage and cell signalling. In the development of the nervous system, they are particularly important as neurons and glia both require extensive membrane synthesis and remodelling. In all animals, lipids are secreted into the circulation in the form of particles containing lipids and proteins, which are called lipoproteins. In Drosophila, lipoproteins are secreted mainly by the fat body, an organ functionally analogous to the adipose tissue and liver in mammals. My project aimed to investigate the role of fat body-derived lipoproteins in the neurodevelopment of Drosophila. To do this, I disrupted lipoprotein metabolism at two different scales: first by preventing the secretion of lipoproteins from the fat body and second by disrupting the local uptake of lipoproteins by the CNS. The goal was to measure the impact of these lipoprotein alterations on systemic and CNS growth, by measuring larval weight and larval brain volume respectively. To disrupt lipoprotein secretion from the fat body, I targeted two different genes via RNA mediated interference (RNAi): lipophorin (apolpp) and microsomal triglyceride transfer protein (Mtp) using a specific fat body GAL4 driver (Lpp-GAL4). Apolpp is functionally similar to apolipoprotein B in mammals, maintaining the structural integrity of the lipoprotein and mediating cargo recognition at destination tissues. Mtp is located in the endoplasmic reticulum and is involved in loading lipoprotein particles with apolipoprotein. I used a Drosophila transgenic line carrying a copy of apolpp tagged with green fluorescence protein (GFP) under its native promoter (apolpp::GFP), which acts as a fluorescent reporter of lipoproteins. I observed that RNAi knockdown of Mtp or Lpp in the fat body strongly decreased larval weight, thus indicating that fat body lipoproteins are critical for systemic growth (Fig.1A-B). In addition, Lpp or Mtp knockdowns severely reduced apolpp::GFP fluorescence in the hemolymph, the functional equivalent of mammalian blood, confirming that apolpp lipoprotein secretion from the fat body into the hemolymph is decreased in both conditions (Fig. 1C). Notably, upon Mtp knockdown, apolpp::GFP signal appears to be retained in the fat body.
Figure 1: Fat Body-derived lipoproteins are critical for systemic and brain growthA) Brightfield images of larvae of the control genotype or knockdown of Lpp-RNAi or Mtp-RNAi under the fat body driver (Lpp-GAL4). B) Weight of larvae 96 hours after larval hatching (ALH). C) Representative images of the distribution of lipoprotein reporter apolpp::GFP (green) in the indicated genotypes. D) Confocal micrograph of larval CNS nuclei stained with DAPI (cyan) of the indicated genotypes. E) Quantification of brain lobe volume.
I then focused on the CNS, by measuring brain lobe volume as a proxy for its growth. I observed that fat body-specific RNAi knockdown of Lpp or Mtp dramatically reduced brain lobe volume (Fig. 1 D-E). Mtp knockdown had a stronger impact on brain volume than larval weight, suggesting that the developing CNS is particularly sensitive to low levels of circulating lipoproteins. Previous work from Suzanne Eaton’s lab has shown that lipoproteins are able to cross the blood-brain barrier (BBB). In Drosophila, the BBB is formed by a specialized subtype of glia that insulates the brain and regulates metabolite exchange with the surrounding hemolymph. I hypothesized that delivery of lipoproteins to the brain may require the lysosome, an organelle responsible for degrading endocytosed cargos. Specifically, I impaired lysosomal acidification by knocking down several subunits of the vacuolar H+ ATPase (V-ATPase) complex in glia and assessed the consequence upon systemic and brain growth. The knockdown of 5 different V-ATPase subunits had a limited impact on the overall weight of the larvae (Fig. 2A). Strikingly, knockdown of four out of the five subunits (Vha16-1, Vha26, Vha68-2 and Vha44) significantly reduced brain lobe volume compared to the control group (Fig. 2B). The fact that brain volume is strongly reduced but not the overall weight of the larvae suggests that lysosomal degradation is important for lipoprotein processing in the brain. To test this hypothesis, I then investigated the apolpp-GFP fluorescent reporter of lipoprotein at the blood brain barrier using confocal microscopy.
Figure 2: Disruption of lysosomal degradation in glia impairs brain growth. A) Weight of larvae 96 hours ALH for knockdown of indicated V-ATPase subunits in glial cells(repo-GAL4); B) Confocal micrograph of larval CNS nuclei stained with DAPI (cyan) of the indicated genotypes. C) Quantification of brain lobe volume.
Notably, knockdown of the V-ATPase subunit in glia resulted in the accumulation of apolpp::GFP puncta in round vacuoles (Fig. 3, white arrowheads) suggesting that undegraded lipoprotein may accumulate in lysosomes. In the future, this could be tested by co-staining using a lysosomal marker.
Figure 3: apolpp accumulates in vacuoles in BBB glia deficient for V-ATPase subunitsConfocal images of blood brain barrier (BBB) glia of glial-specific knockdown of the indicated V-ATPase subunits. Lipoproteins are visualised with apolpp::GFP, a protein fusion under endogenous apolpp promoter (green), nuclei are labelled with DAPI (cyan) and lipid droplets with Lipidtox (magenta). Arrowheads point to cytoplasmic accumulation of apolpp::GFP in glial cells deficient for indicated V-ATPase subunits.
This project provided me with a fascinating immersion into the process of scientific discovery and gave me a deeper appreciation for how model organisms can illuminate big questions in neuroscience. It has helped me cement my decision to pursue a research career in neuroscience. I am especially grateful to my supervisor, Victor Girard, for guiding me through this fascinating project and Alex Gould and the whole lab for their support and encouragement throughout the nine weeks. I would also like to extend my gratitude to The Francis Crick Institute and to the MRF Rosa Beddington Fund for funding my project and allowing me the opportunity to contribute to developmental biology research.
Tsetse flies (Glossina spp.) are the sole vectors of African trypanosomiasis – sleeping sickness in humans and nagana in livestock. The midgut is the site of blood digestion, symbiont interactions, and trypanosome establishment, making it a central organ to study both vector physiology and vector–parasite interactions (Geiger et al. 2013). Understanding the gene expression profiles and cellular organisation underlying midgut function may bring us one step closer to developing new vector control strategies.
During my summer studentship at the Francis Crick Institute, supported by the MRF Rosa Beddington Fund, I worked in Prof. Irene Miguel-Aliaga’s Organ Development and Physiology Laboratory. Mentored by Dr. Mireia Larrosa-Godall, I was able to contribute to ongoing studies of digestive tract physiology in the tsetse fly (Glossina morsitans morsitans).
Understanding organ function requires knowing which cell types are present and how they specialise – diversity that arises not from differences in genetic code but from distinct gene expression patterns. Our lab investigates how gut cells integrate cues, coordinate across tissues, and remodel the organ in response to diet, microbes, sex, or reproduction. While previous research in Drosophila melanogaster has identified different intestinal cell types and their pertinent genetic markers, the cell population of the tsetse fly gut remains unexplored. My project set out to address this gap by characterising candidate intestinal cell marker genes – those showing restricted expression in single-cell RNA-seq clusters, and/or known markers for specific intestinal cell types in D. melanogaster. HCR RNA-FISH was then employed to visualise their spatial mRNA transcript distribution within the gut.
We selected several candidate epithelial marker genes that have well-established roles in D. melanogaster. Enteroendocrine cell fate is specified by the transcription factor gene prospero (Lim et al. 2020), while enterocyte differentiation and microbial tolerance are regulated by nubbin (Widad Dantoft et al. 2013). Maintenance of intestinal stem cell identity is governed by escargot, a canonical intestinal stem cell (ISC) marker (Korzelius et al. 2014), that was not detected in the lab’s single-cell RNA-seq dataset (although this may have been influenced by incomplete 3′ UTR annotation). Beyond the established markers, peptidoglycan recognition protein – pgrp (Bosco-Drayon et al. 2012), involved in the immune pathway, was selected for its cluster-specific expression. In addition, tsetseEP, which encodes a midgut protein with structural similarity to trypanosome proteins and is relevant to vector–parasite interactions (Chandra et al. 2004), and cg12541, a gene of undefined function in D. melanogaster, were also included.
To study the spatial expression of these genes, I started by characterising their mRNA sequence to experimentally confirm transcript isoforms for downstream applications such as probe design. Unlike in other species, the genome assembly available for Glossina morsitans morsitans has fewer predicted genes relative to the more recently available genome assemblies (Attardo et al. 2019). Hence, additional sequencing data would be informative. For this purpose, I designed primers against the predicted sequences and amplified the regions of interest by RT-PCR from Glossina morsitans morsitans cDNA. PCR products were visualised on agarose gels to confirm fragment size, and the amplified DNA was purified. In cases where direct sequencing was not possible, amplicons were cloned by bacterial transformation and screened by colony PCR to identify positive colonies. Verified inserts were then submitted for Sanger sequencing, yielding high-quality reads that were assembled and annotated. In addition to identifying indels specific to the lab’s wild-type strain, four previously unannotated isoforms of prospero were characterised, revealing additional isoform diversity that may regulate enteroendocrine cell specification. The validated sequences (Fig. 1) provided a reliable foundation for the design of HCR probes.
Figure 1. Schematic representation of the transcripts of six candidate intestinal cell marker genes in Glossina morsitans morsitans.
Orange boxes indicate common open reading frames (ORFs), white boxes indicate untranslated regions (UTRs), grey boxes indicate predicted ORFs outside of the sequenced region, blue boxes indicate male-specific ORFs, and the green box indicates a female-specific ORF. Double slashes on introns denote regions longer than 2 kb that are collapsed for clarity. Directional arrows mark sequencing primer positions. Multiple transcript isoforms are shown for prospero (F1, Cn1–2, M1–M2); F = female, M = male, Cn = common. Scale bar represents 500 bp.
In this project, I performed HCR RNA-FISH on two marker genes previously characterised in other insect species – nubbin and escargot – which were expected to label differentiated enterocytes and ISCs, respectively. In this method, whole guts were dissected in PBS and fixed in 4% paraformaldehyde, then incubated with probes complementary to the target mRNA transcripts, along with fluorescent hairpins that enable subsequent chain reaction amplification. Bound probes triggered a chain reaction of fluorescent hairpins that polymerised directly at the mRNA site, producing a strong signal. The tissue was then imaged by confocal microscopy, where the amplified mRNA transcripts appear as bright fluorescent regions within the cell cytoplasm and in some cases within the cell nucleus. This approach offers the first spatial view of mRNA transcription in the tsetse gut.
The nubbin mRNA was detected as nuclear-localised fluorescent signal in a subset of epithelial cells in the middle and posterior midgut (Fig. 2). Its detection in tsetse therefore points to the presence of enterocyte-like cells in these regions. This localisation is consistent with the physiological role of the mid and posterior midgut in nutrient uptake and digestion. By contrast, no nubbin signal was detected in the anterior midgut, consistent with its role as a site of initial blood processing rather than absorption (Wigglesworth, 1929), although this region may contain enterocytes of distinct identity that do not express nubbin.
Figure 2. nubbin-expressing cells were identified in the Glossina morsitans morsitans middle midgut and posterior midgut regions.
Confocal z-stacks of female anterior (AM), middle (MM), and posterior midgut (PM) showing nubbin transcripts (yellow) and nuclei counterstained with DAPI (blue). Below, corresponding monochrome panels display nubbin transcript signal in black. Scale bars represent 50 μm for all images. Maximum intensity projections at 20x magnification are shown. Representative image from n = 5.
In contrast, escargot transcripts were not observed in any of the epithelial cells of the midgut (Fig. 3A). Together with their absence from the lab’s single-cell dataset, this supports the possibility that tsetse midguts may lack ISCs. Consistently, pH3 staining – a marker of mitotic activity and therefore used to identify dividing ISCs in the insect gut – did not reveal proliferating cells in the midgut. Positive staining was observed in larval wing discs, suggesting that the absence of pH3 staining in the gut is due to a lack of ISCs (Fig. 3B). Instead, the midgut may depend on alternative mechanisms to maintain gut integrity such as endoreplication, as has been proposed for other blood-feeding insects (Taracena-Agarwal et al. 2024). Nonetheless, it cannot be ruled out that escargot expression occurs at very low levels, within rare populations below detection, or that it is not a marker of ISC identity in the tsetse midgut. Future work will be needed to explore these possibilities.
Figure 3. escargot-expressing cells were not identified throughout the Glossina morsitans morsitans midgut regions.
(A) Confocal z-stacks of female anterior (AM), middle (MM), and posterior midgut (PM) showing escargot transcripts (red) and nuclei counterstained with DAPI (blue). Maximum intensity projections at 20× magnification are shown. (B) Immunostaining for phospho-histone H3 (pH3, green) in the larval wing discs (used as a positive control) and adult midgut. Nuclei are counterstained with DAPI (blue in midgut, purple in wing discs). pH3 staining and imaging performed by Lisa Gartner. Scale bars represent 50 μm for all images.
Together, these results provide the first spatial map of nubbin and escargot expression in the tsetse midgut and establish HCR RNA-FISH as a pipeline for visualising gene expression in this species and other blood-feeding insects. This work establishes a foundation for tsetse fly gut physiology, an organ that may influence both reproduction and pathogen interactions, and thus represents a potential target for vector control.
I am very grateful for the opportunity to contribute to research in the Organ Development and Physiology Laboratory at the Francis Crick Institute. Being supported by the MRF Rosa Beddington Fund has been an honour and a formative step in my development as a scientist. This project has been a defining experience, strengthening my commitment to pursue a career in research. I would like to thank the Miguel-Aliaga Lab for their support and for welcoming me into such a stimulating research environment. I am especially grateful to my supervisor, Dr. Mireia Larrosa-Godall, for her guidance and mentorship throughout my project, and to Lisa Gartner for also welcoming me into the fascinating project and contributing the pH3 staining to this study.
Reference list
Attardo, G.M., Abd-Alla, A.M.M., Acosta-Serrano, A., Allen, J.E., Bateta, R., Benoit, J.B., Bourtzis, K., Caers, J., Caljon, G., Christensen, M.B., Farrow, D.W., Friedrich, M., Hua-Van, A., Jennings, E.C., Larkin, D.M., Lawson, D., Lehane, M.J., Lenis, V.P., Lowy-Gallego, E. and Macharia, R.W. (2019). Comparative genomic analysis of six Glossina genomes, vectors of African trypanosomes. Genome Biology, 20(1). doi:https://doi.org/10.1186/s13059-019-1768-2.
Beebe, K., Lee, W.-C. and Micchelli, C.A. (2010). JAK/STAT signaling coordinates stem cell proliferation and multilineage differentiation in the Drosophila intestinal stem cell lineage. Developmental Biology, 338(1), pp.28–37. doi:https://doi.org/10.1016/j.ydbio.2009.10.045.
Bosco-Drayon, V., Poidevin, M., Boneca, I., Narbonne-Reveau, K., Royet, J. and Charroux, B. (2012). Peptidoglycan Sensing by the Receptor PGRP-LE in the Drosophila Gut Induces Immune Responses to Infectious Bacteria and Tolerance to Microbiota. Cell Host & Microbe, 12(2), pp.153–165. doi:https://doi.org/10.1016/j.chom.2012.06.002.
Chandra, M., Liniger, M., Tetley, L., Roditi, I. and Barry, J.D. (2004). TsetseEP, a gut protein from the tsetse Glossina morsitans, is related to a major surface glycoprotein of trypanosomes transmitted by the fly and to the products of a Drosophila gene family. Insect Biochemistry and Molecular Biology, 34(11), pp.1163–1173. doi:https://doi.org/10.1016/j.ibmb.2004.07.004.
Geiger, A., Fardeau, M.-L., Njiokou, F. and Ollivier, B. (2013). Glossina spp. gut bacterial flora and their putative role in fly-hosted trypanosome development. Frontiers in Cellular and Infection Microbiology, 3. doi:https://doi.org/10.3389/fcimb.2013.00034.
Korzelius, J., Naumann, S.K., Loza‐Coll, M.A., Chan, J.S., Dutta, D., Oberheim, J., Gläßer, C., Southall, T.D., Brand, A.H., Jones, D.L. and Edgar, B.A. (2014). Escargot maintains stemness and suppresses differentiation in Drosophila intestinal stem cells. The EMBO Journal, 33(24), pp.2967–2982. doi:https://doi.org/10.15252/embj.201489072.
Lim, S.Y., You, H., Lee, J., Lee, J., Lee, Y., Lee, K.-A., Kim, B., Lee, J.-H., Jeong, J., Jang, S., Kim, B., Choi, H., Hwang, G., Choi, M.S., Yoon, S.-E., Kwon, J.Y., Lee, W.-J., Kim, Y.-J. and Suh, G.S.B. (2020). Identification and characterization of GAL4 drivers that mark distinct cell types and regions in the Drosophila adult gut. Journal of Neurogenetics, 35(1), pp.33–44. doi:https://doi.org/10.1080/01677063.2020.1853722.
Miguel-Aliaga, I., Jasper, H. and Lemaitre, B. (2018). Anatomy and Physiology of the Digestive Tract of Drosophila melanogaster. Genetics, 210(2), pp.357–396. doi:https://doi.org/10.1534/genetics.118.300224.
Taracena-Agarwal, M.L., Hixson, B., S. Nandakumar, Girard-Mejia, A.P., Chen, R.Y., Huot, L., Padilla, N. and N. Buchon (2024). The midgut epithelium of mosquitoes adjusts cell proliferation and endoreplication to respond to physiological challenges. BMC Biology, 22(1). doi:https://doi.org/10.1186/s12915-023-01769-x.
Widad Dantoft, Davis, M.M., Lindvall, J.M., Tang, X., Uvell, H., Junell, A., Beskow, A. and Ylva Engström (2013). The Oct1 homolog Nubbin is a repressor of NF-κB-dependent immune gene expression that increases the tolerance to gut microbiota. BMC Biology, 11(1). doi:https://doi.org/10.1186/1741-7007-11-99.
Wigglesworth, V.B. (1929). Digestion in the Tsetse-Fly: A Study of Structure and Function. Parasitology, 21(3), pp.288–321. doi:https://doi.org/10.1017/s0031182000022988.
The Kahneman Chronicles #2: Loss Aversion and the Art of Quitting
Daniel Kahneman (1934-2024) was a legendary psychologist who revolutionized our understanding of human decision-making and became known as the “grandfather of behavioral economics.” Awarded the 2002 Nobel Prize in Economics, Kahneman’s groundbreaking research with Amos Tversky revealed systematic biases and mental shortcuts leading people to make irrational choices.
This article series imagines what would transpire when Daniel Kahneman took a sabbatical and worked in a fly lab. Part of “The Kahneman Chronicles: Lessons from a Fly Lab” – A report from our imaginary interdisciplinary fellowship program
Three months into Kahneman’s sabbatical, grad student Tobias stared at yet another failed Western blot, its blank lanes replacing the crisp bands he expected.
“That’s the fourteenth attempt,” Kahneman observed quietly from behind him, notebook in hand.
“I know,” Tobias said. “But I’m so close. I’ve invested eight months to optimise this protocol. I need just one more try with a fresh antibody. Maybe two more.”
Kahneman’s eyebrows rose slightly. “Interesting. Tell me—with what you know now,if you were starting today, would you choose this approach?”
Tobias stared back blankly, silent.
To persist or to quit?
Every lab has them. The experiments that took years. The “almost working” protocols. Projects which drained countless hours, reagents, and emotional energy. And yet, despite mounting evidence suggesting a different path might be wiser, we persist.
“You’re all experiencing two powerful forces,” Kahneman announced at our next lab meeting. “Loss aversion and the sunk cost fallacy. Stopping a project means admitting loss, accepting pain. And we want to avoid pain.”
Loss Aversion: The tendency to prefer avoiding losses over acquiring equivalent gains. Losing $100 feels roughly twice as bad as gaining $100 feels good. The pain of abandoning a project outweighs the potential joy of switching to something promising.
Sunk Cost Fallacy: The tendency to continue investing in something because of past investments, even when cutting losses would be more rational. “I’ve already spent six months on this—I can’t quit now!” But those six months are gone regardless of what you do next.
“Here’s what makes your situation uniquely difficult,” Kahneman explained, drawing on the whiteboard. “Science indeed requires persistence. The breakthroughs do sometimes come on that fifteenth attempt. We celebrate stories of stubborn researchers,who ignored skeptics and proved everyone wrong.”
Postdoc Aisha nodded vigorously. “Exactly! My PI always says ‘science rewards persistence.’ How do we know when we’re being persistent versus just throwing good time after bad?”
Kahneman smiled. “That’s the million-dollar question.Phillip, from your lab, spent eleven months troubleshooting that impossible imaging setup. Everyone told him to quit. But he steadily made incremental improvement—each troubleshooting step revealed new information. New mistakes made and rectified.
And in month twelve, he figured it out. Now it’s the lab’s most cited method paper.”
“But”, he continued, ” Tobias isn’t just continuing because science might work. He’s continuing because admitting loss means admitting a personal failure. His System 1 screams ‘you can’t let all that work be for nothing!'”
This was the uncomfortable truth: there’s no algorithm to tell you whether you’re Phillip or Tobias.
The antidote of six questions
“I wish some GPT will tell you whether to persist or quit,” Kahneman admitted. “But some tools can help you think more clearly about it. Here are six questions I want you to ask about any struggling project.”
He wrote on the whiteboard:
The Fresh Eyes Test: “If a new student joined tomorrow and you described this project, would you assign it to them? Or would you say, ‘Actually, we have better projects available’?”
The Sunk Cost Separator: “Imagine all the time you’ve spent is gone—poof, erased. With what you know NOW, purely about the future, would you invest the next three months in this approach?”. This question removes the weight of past investment. It forces you to evaluate only future value.
The Diminishing Returns Check: “Are your results improving with each iteration, or are you getting the same null results in different fonts?”
The Alternative Opportunity Cost: “What else could you be doing with this time? Not abstract ‘anything else,’ but specifically, what’s the second-best use of your next three months?”. This can help you see what you might be sacrificing.
The Motivation Test:“If this project would definitely fail, and you knew it would fail, would you feel relieved or devastated?”If “relieved,” you have your answer.
The Outside View “What would you tell your best friend if they described this exact situation to you?” We’re terrible at evaluating our own situations but remarkably clear-sighted about others’ problems. Use that. That’s the purpose of lab meetings, conferences, poster presentations and talks.
Conscious pivoting
“Pivoting doesn’t mean your previous work was wasted. They’re only wasted if you learn nothing. If it helps, take a moment to say farewell and grieve over the failure, but then decide to stop”
Yan spoke up. “So how do I know if I quit too early? What if I abandon something that would have worked?”
“You don’t know, no one knows,” Kahneman said bluntly. “That’s the brutal reality. You’re making decisions under uncertainty. The goal isn’t to eliminate uncertainty. It’s to make the decision consciously, based on forward-looking analysis rather than backward-looking regret aversion.”
A month later
Tobias came to Kahneman with a decision. “I’m stopping the Western blots. But I’m not abandoning the question—I’m switching to a mass spec approach. It’ll take time to learn, but the core science is still sound.”
“How do you feel?” Kahneman asked.
“Honestly? Relieved. And excited. Which tells me something.”
Across the lab, grad student Aisha had reached the opposite conclusion about her struggling project. “I’m continuing,” she announced. “But I’m setting a deadline: three more months with weekly milestones. If I’m not seeing incremental progress, I pivot.”
Kahneman nodded approvingly. “Notice what you both did? You made conscious, analytical decisions. You acknowledged the sunk costs but didn’t let them drive your choice. You looked forward, not backward. Whether your projects succeed or fail, you’re making better decisions.”
Some successful scientists succeeded because they persisted. Others succeeded because they quit and tried something else. Both paths lead to success stories. Both paths lead to failures. Sometimes keep going and sometimes, pivot. But do so consciously.
Have you experienced similar pain in letting go of projects or ideas? Do share in the comments. What else did the Prof. Kahneman advise us on? Stay tuned for the next article in the series.
Sameer Thukral is a post doc in the lab of Yu-Chiun Wang at RIKEN-BDR, Kobe, Japan, where he loves discussing science in the healthy and respectful lab environment. He is a developmental biologist with a focus on mechanics of yolk-blastoderm interactions. He is also the co-founder of BDR-Launchpad, a post-doc network for supporting ECRs with the hidden curriculum of science.
The observations made here are his own and do not reflect the opinions of the employer. This article was written by Sameer Thukral, with formatting, structuring and framing support of Claude AI.
At the speakers’ discretion, the webinar will be recorded to view on demand. To see the other webinars scheduled in our series, and to catch up on previous talks, please visit: thenode.biologists.com/devpres
Before diving into the science and the path we took to reach our most recent publication in Development1, let me (Anne Schmidt, senior CNRS scientist, France) take a few lines to introduce the people behind the work.
The first author, Léa Torcq, studied mathematics and developmental biology. Léa began her PhD in October 2019, just a few months before the COVID pandemic. Our second key contributor is Catherine Vivier, our invaluable technician. The third and fourth members of our team are highly dedicated engineers from our platforms, Sandrine Schmutz and Yann Loe-Mie, who brought their excellent expertise in FACS-mediated cell sorting and bioinformatics, respectively. All three of them are staff members of the Pasteur Institute in Paris, France.
Léa and I will take turns sharing our exciting and fruitful collaboration aimed at tracking emerging and newly born hematopoietic stem cells to their implantation sites in developmental niches, using the zebrafish embryo and larva.
Anne: Our project began when — with my background in cellular and bio-membrane dynamics — I decided to investigate fundamental aspects of the cell biology of pre-hematopoietic stem cell emergence. This intriguing and unusual process, first visualized by Karima Kissa and Philippe Herbomel 15 years ago in the zebrafish embryo, is referred to as the Endothelial-to-Hematopoietic Transition or EHT2. To our knowledge, this unusual way of emerging from a flat tissue, where the cell bends outwardly from the aortic plane toward the sub-aortic space, appears to be specific to zebrafish (until it is observed in another tissue or species!).
While we began to unveil some fundamental aspects of these intriguing mechanics in 20183 (see our previous ‘Behind the Paper’ story), we questioned how the luminal membrane of these emerging cells is maintained throughout emergence and how it evolves after completion — with the key feature being the control of apico-basal polarity. Importantly, the evolution of this luminal membrane after release may influence the cell’s behavior, including its migration capacity (for example, if used as a membrane reservoir for cell locomotion), its signaling features (if recycled and/or degraded), and ultimately, its fate.
To tackle these ideas, I developed transgenic lines expressing a well-characterized apical marker, podocalyxin-l2, fused with eGFP (eGFP-podxl). Interestingly, using this line, EHT-undergoing cells imaged with confocal microscopy exhibited obvious asymmetric eGFP-podxl localization, with enrichment at the luminal membrane4. Astonishingly, the apical/luminal membrane is extremely dynamic (see Fig. 1) and eventually collapses into a pseudo-endocytic compartment after chasing engulfed intra-aortic fluid, which persists for several hours after release from the aortic floor (a post-EHT signature). This showed that apico-basal polarity is a key feature of EHT cells, maintaining a large apical domain until release, which is unconventional for a cell extruding from a tissue5. Perhaps this is the only way a cell can extrude from a flat tissue under strong mechanical tension (the tension exerted on the aortic wall by blood flow and its associated forces6), but in fact, it is not! Another outcome from our eGFP-podxl line unambiguously revealed another type of emergence dynamics, which showed no obvious apico-basal polarity. These emerging cells maintain a round shape (not resulting from recent mitosis), with endothelial neighbors crawling on their membrane facing the aortic fluid4. These two types of emerging cells, which we called EHT pol+ and EHT pol- cells (for polarized and unpolarized cells, based on podocalyxin localization), suggested that they may have different fates.
Figure 1: Series of z planes showing the dynamics of the EHT cell apical/luminal membrane labelled with eGFP-podocalyxinL2. Spinning disk confocal images obtained with Tg(kdrl:Gal4;UAS:RFP;4xNR:eGPF-podxl2) 50-55 hpf embryos (green: cellular membranes; red: cytosolic RFP). A, single z plane of a longitudinal section of the dorsal aorta (aortic lumen) showing one pre-hematopoietic stem or progenitor cell undergoing EHT (white delimited area on the right). Note the inward bending of the cell, toward the sub-aortic space. B, cropped views of single z planes extracted from a time-lapse sequence starting with the timing point visualized in the field delimited in (A). Images were acquired with 7 minutes intervals, from t=00.00 to t=04.47 hours as indicated in panels 1 and 42, respectively. Numbers 1 to 42 correspond to the progression of the time-lapse sequence throughout time. Note the enrichment of eGFP-podxl2 in the apical/luminal membrane as well as its remarkable dynamics (ex: compare panel 1 with panels 4, 9-12, 14-18). Note also the apparent regression of the apical/luminal membrane in panel 42, indicating that the cell has completed emergence from the aortic floor (we make the interpretation that the cell has detached from the floor in panel 30). Scale bar: 12 µm.
Besides characterizing junctional dynamics at the interface between EHT cells and endothelial neighbors, Léa’s aim was to tackle the question: are EHT pol+ and EHT pol- cells leading to different progenies? The idea was to set up single-cell photoconversion of EHT-undergoing cells, exploring the niches into which progenies establish throughout early larvae (an invaluable advantage of zebrafish, which develops quickly yet remains small) and characterizing their molecular signatures using single-cell RNAseq (sc-RNAseq).
Léa: I joined the lab as a Master’s student to work on this project in January 2019. I had previously studied EHT in Thierry Jaffredo’s lab, conducting work on self-organizing quail embryo explants in vitro. Although such models are fundamental to scientific discovery, I wanted to move toward more physiological, in vivo approaches. When I met Anne and she showed me the movies generated through live imaging of transgenic zebrafish embryos, I was instantly fascinated by this beautiful – both scientifically and aesthetically – approach. I also quickly discovered that Anne was a unique kind of senior researcher. She remains actively involved in performing and analyzing experiments at length with a combination of youthful drive for science with wise meticulousness, which convinced me to follow my initial internship with a PhD, with Anne as my advisor.
I was also drawn to this project because it gave me the opportunity to learn many different techniques, ranging from live imaging to scRNAseq and transgenesis. It came with challenges in optimizing and analyzing these diverse experiments, compounded by the COVID lockdown during most of 2020. Nevertheless, we persevered, and I was fortunate to receive invaluable help from several people, particularly our co-authors. Catherine taught me how to perform in situ hybridization and set up single molecule fluorescence in situ hybridization (smFISH), using RNAScope. Sandrine, from our institute’s cytometry platform, spent around 100 hours sorting cells for subsequent scRNAseq experiments. As for Yann, he originally helped set up the analysis pipeline for MARS-seq and provided guidance when I began training myself in scRNA-seq analysis.
Overall, we used nearly 400 embryos for photoconversion of single cells based on their morphology as they emerged from the aorta. Subsequently, larvae were used to track migration patterns and build precise lineage trees. We also index-sorted the progenies of 2,036 photoconverted cells and generated MARS-seq libraries from them. Separately, we used gata2b and cd41 reporter lines and 10X Chromium to generate a complementary scRNA-seq dataset of more than 30,000 cells, encompassing the whole hematopoietic lineage sorted by their niche of origin. Our main discovery was the differential fate of EHT pol+ and EHT pol- cells, with a bias regarding the lymphoid lineage. We identified different propensities to seed the thymus as well as different abilities to differentiate into T-lymphocytes. Moreover, our work contributes to the characterization of zebrafish hematopoietic cell types with new insights on the origin of some populations, like the ILC2-like and ILC3-like cells, never before observed at such early developmental stages.
Anne: Léa’s hard experimental and bioinformatic work has been extremely fruitful. From our single cell pipelines and their integration, we retrieved informative signatures of Hematopoietic Stem and Progenitor Cell (HSPC) populations. These included the transcription factor gata2b7 (which is upstream of runx1, a transcription factor essential for hematopoiesis8) and podocalyxin/cd34. Intriguingly, we found that in addition to embryonic HSPCs (eHSPCs) and other multipotent progenitors, gata2b is also expressed in sub-populations of ILC2-like cells enriched in the anterior/trunk region of the larvae, and of young eosinophils. We discovered that eosinophils possess the unique property of differentially expressing genes related to extracellular niche/matrix functions, including serine protease inhibitors of the spink2 family, timp4.2 (an inhibitor of metalloproteases), as well as one specific member of the MFAP4 locus. We then used these markers to investigate the localization of hematopoietic populations through whole-mount in situ hybridization. With Catherine’s expertise, we developed RNAscope applied to zebrafish. While whole-mount RNAscope had rarely been used for zebrafish embryos and larvae at that time – essentially because chromogenic and/or fluorescent in situ hybridization using long antisense nucleotide probes were routinely used and at relatively low cost –, it proved to be a great decision. Because it provided a high signal-to-noise ratio and sensitivity, RNAscope allowed us to investigate cells implanted in niches throughout the entire early larval body, including the pronephros region, which is challenging because it requires deep penetration of probes and low background (see our recent technical paper 9).
With the timp4.2 marker highly expressed in eosinophils, we found an intriguing accumulation of cells almost exclusively in the most anterior region of the pronephros, in the 5 dpf larva. These cells, with a maximum of 15 per animal in that region (on average more than in the trunk and the Caudal Hematopoietic Tissue (CHT)), also faintly express eGFP driven by an enhancer of the hematopoietic transcription factor runx1, confirming their hematopoietic origin (see Fig. 2 and Movie 1). This pointed to sub-compartmentation of the pronephros niche. Currently, we do not know if these cells, presumably eosinophils (or progenitors), home there for maturation and/or if they contribute to building a sub-niche hosting specific hematopoietic cell subtypes. Anyhow, these results highlight the functional complexity of the developing pronephros niche and point to the importance of investigating micro-environmental properties supporting the differentiation and/or maintenance of specific hematopoietic populations.
Figure 2: Whole-mount in situ hybridization revealing timp4.2 mRNA expression in hematopoietic and vascular cells using RNAscope. A, C, D, Representative images (Imaris 3D-rendering) of RNAscope ISH for timp4.2 (magenta spots) in 5 dpf Tg(runx1+23:eGFP) larvae. Images show the pronephros region (A, see also Movie 1), the posterior trunk region (C, above the elongated yolk) and the CHT (D). a’, c’, d’ are magnifications of regions outlined with white dashed boxes in (A, C, D), respectively. eGFP positive hematopoietic cells were segmented (green contours). White arrows point at timp4.2 positive hematopoietic cells. The sub-aortic clusters are delimited by yellow dashed lines and the gut by magenta dashed lines. B, Relative position of eGFP positive cells along the antero-posterior axis of the pronephros (n=681 timp4.2– cells, n=46 timp4.2+ cells). E, Percentage of eGFP positive hematopoietic cells expressing timp4.2, n=6 larvae for pronephros, n=3 for trunk and CHT regions. (B, E) Two-sided Wilcoxon tests. NC: notochord. Scale bars: 10 µm.
Movie 1: 3D visualization of RNAscope in situ hybridizations for timp4.2. Timp4.2 (in magenta) in the pronephros region of Tg(runx1+23:eGFP) 5 dpf larvae, 3 representative replicates are shown. Bottom row shows magnifications of the top row. Hematopoietic cells in the pronephros are delineated (green contours). Scale bars: 10 µm.
Finally, the most unexpected results came when using the gata2b probe. We detected strong expression of this transcription factor in endothelial cells of the supra-intestinal artery (SIA), a small vessel located just above the intestinal tract and beneath the posterior cardinal vein (for detailed anatomy, see Isogai et al10). We obtained these results in March 2023, more than 2 years ago and about a year and a half before submitting our paper to Development. Importantly, our images unambiguously showed that not only do SIA endothelial cells express gata2b, but so do other cells in their direct vicinity, even contacting the SIA wall. These cells also express eGFP driven by the vascular kdrl promoter, and it appeared that many of them express eGFP at levels comparable to SIA endothelial cells.
Léa: When we realized this, we considered that the SIA region might not only be a niche for hematopoietic stem and progenitor cells and more differentiated cells whose ancestors emerged from the dorsal aorta days before (e.g., ILC-like cells with immune functions in the gut11), but that these cells might also derive directly from the SIA wall itself! To reinforce our results, I quantified the number of gata2b-positive cells in the direct surroundings of the SIA as well as near the dorsal aorta, showing that the SIA region is significantly enriched in gata2b cells compared to the dorsal aorta. After 3D segmentation of the cells with Imaris, I quantified their eGFP signals (driven by the kdrl promoter) and found that gata2b-positive cells near the SIA express comparable levels of eGFP to SIA endothelial cells (with no such cells around the dorsal aorta). This suggests they are relatively newly born cells whose eGFPcontent has not been diluted by division cycles, reinforcing the idea that they may originate from the SIA endothelium.
Anne: All this evidence supports the hypothesis that the SIA may be hemogenic. Due to the constant movement of the gut beneath the SIA, we struggled to provide high quality time-lapse sequences for our paper in Development (even acquiring a single complete z-stack was difficult). However, we obtained discontinuous images over relatively short periods of up to 2 hours that strongly suggest emergence from the SIA wall (see Fig. 3). Importantly, cells undergoing apparent emergence remained very ‘sticky’ to the SIA wall, making it difficult to confirm they fully completed EHT. Our results clearly demonstrate that the SIA region is at least a niche hosting HSPCs and suggest that these may be born from this small artery. Hence, the SIA may be hemogenic, a potential novel finding requiring further validation. As discussed in our Development paper1, this validation will require characterizing the SIA hemogenic endothelium and the fate of the derived EHT cells at the single-cell level.
Figure 3: Evidence of emergence from the SIA endothelium. Top panel: schematic representation of a 5 dpf larva (reproduced with modifications from Schmidt, 2022, doi:10.7554/eLife.64835); red line = aorta, blue line = vein, magenta line = SIA. (a – d’), spinning disk confocal microscopy of a 5 dpf Tg(kdrl:eGFP) zebrafish larva, in the upper part of the trunk region (delimited in the cyan box of the upper cartoon). Panel a (z projection), the upper part of the trunk region encompassing the dorsal aorta, the posterior cardinal vein, and the SIA with the latter passing beneath the swim bladder (SB, on the left side of the image). White and magenta asterisks indicate cells expressing eGFP at apparently comparable level than SIA endothelial cells and that are contacting the SIA wall (note that no such cells are in contact with the ventral floor of the dorsal aorta). (b – d’), single z planes extracted from the z stack projected in (a), with images magnified from the region in (a) delimited by the white rectangle and showing the cell surrounded by the green rectangle in (a) and undergoing emergence between 0 min (b, b’), 10 min (c, c’), and 20 min (d, d’). Panels (b, b’), (c, c’), and (d, d’) are images separated by 1 mm depth in z. Green arrows point at the connection of the emerging cell with the aortic lumen; magenta arrows point at the disappearance of this connection, which suggests completion of the emergence. Scale bar: 20 µm.
This story behind our paper in Development summarizes an exciting research journey that led to several previously undescribed findings. This was made possible by assembling a team of passionate and efficient people and pushing forward the resolution of our analyses, including technically demanding single cell photoconversion, multiple single-cell RNAseq approaches, and powerful smFISH technology using a new generation of small, highly specific probes (we’ve significantly contributed to increasing the number of zebrafish hematopoietic probes in the ACD catalogue!).
Finally, we are convinced that our work opens new avenues for exciting future discoveries in the fields of hematopoietic stem cells and vascular biology.
References
1. Torcq, L., Vivier, C., Schmutz, S., Loe-Mie, Y., and Schmidt, A.A. (2025). Single-cell and in situ spatial analyses reveal the diversity of newly born hematopoietic stem cells and of their niches. Development 152, dev204454. https://doi.org/10.1242/dev.204454.
2. Kissa, K., and Herbomel, P. (2010). Blood stem cells emerge from aortic endothelium by a novel type of cell transition. Nature 464, 112–115. https://doi.org/10.1038/nature08761.
3. Lancino, M., Majello, S., Herbert, S., De Chaumont, F., Tinevez, J.-Y., Olivo-Marin, J.-C., Herbomel, P., and Schmidt, A. (2018). Anisotropic organization of circumferential actomyosin characterizes hematopoietic stem cells emergence in the zebrafish. Elife 7, e37355. https://doi.org/10.7554/eLife.37355.
4. Torcq, L., Majello, S., Vivier, C., and Schmidt, A.A. (2024). Tuning apicobasal polarity and junctional recycling in the hemogenic endothelium orchestrates the morphodynamic complexity of emerging pre-hematopoietic stem cells. Elife 12, RP91429. https://doi.org/10.7554/eLife.91429.
5. Staneva, R., and Levayer, R. (2023). Cell polarity and extrusion: How to polarize extrusion and extrude misspolarized cells? Curr Top Dev Biol 154, 131–167. https://doi.org/10.1016/bs.ctdb.2023.02.010.
6. Campinho, P., Vilfan, A., and Vermot, J. (2020). Blood Flow Forces in Shaping the Vascular System: A Focus on Endothelial Cell Behavior. Front Physiol 11, 552. https://doi.org/10.3389/fphys.2020.00552.
7. Butko, E., Distel, M., Pouget, C., Weijts, B., Kobayashi, I., Ng, K., Mosimann, C., Poulain, F.E., McPherson, A., Ni, C.-W., et al. (2015). Gata2b is a restricted early regulator of hemogenic endothelium in the zebrafish embryo. Development 142, 1050–1061. https://doi.org/10.1242/dev.119180.
8. Gao, L., Tober, J., Gao, P., Chen, C., Tan, K., and Speck, N.A. (2018). RUNX1 and the endothelial origin of blood. Exp. Hematol. 68, 2–9. https://doi.org/10.1016/j.exphem.2018.10.009.
9. Torcq, L., and Schmidt, A. (2025). Single Molecule Fluorescence In Situ Hybridization Using RNAscope to Study Hematopoietic and Vascular Interactions in the Zebrafish Embryo and Larva. BIO-PROTOCOL 15. https://doi.org/10.21769/BioProtoc.5269.
10. Isogai, S., Horiguchi, M., and Weinstein, B.M. (2001). The Vascular Anatomy of the Developing Zebrafish: An Atlas of Embryonic and Early Larval Development. Developmental Biology 230, 278–301. https://doi.org/10.1006/dbio.2000.9995.
11. Hernández, P.P., Strzelecka, P.M., Athanasiadis, E.I., Hall, D., Robalo, A.F., Collins, C.M., Boudinot, P., Levraud, J.-P., and Cvejic, A. (2018). Single-cell transcriptional analysis reveals ILC-like cells in zebrafish. Sci Immunol 3. https://doi.org/10.1126/sciimmunol.aau5265.
A high magnification video of a zebrafish embryo demonstrates sensory neurogenesis in the developing nose (olfactory epithelium), with newly forming neurons labeled in orange and blue cells indicating high Notch signaling activity. The developing eye is also visible nearby. The olfactory epithelium houses remarkable levels of neuroregeneration, including in humans, and is a robust model for investigating the molecular pathways that drive continuous neuronal renewal.
Where can this be found?
Zebrafish are ray-finned fish that are native to freshwater habitats in South Asia and are widely used as vertebrate model systems due to their high degree of genetic similarity to humans. We use a suite of tools to genetically manipulate the organisms, and the optically transparent embryos are amenable to high-resolution microscopy.
How was this taken?
We performed live confocal microscopy of transgenic zebrafish embryos at 2 days post-fertilization (dpf). The embryos expressed red fluorescent protein (orange) in olfactory sensory neurons and destabilized green fluorescent protein (blue) in cells with active Notch signaling. Images were acquired at regularly spaced time intervals for 15 hours using a Zeiss LSM 800 confocal microscope and stitched together to make this timelapse video.
What happens during olfactory sensory neuron (OSN) development?
We discovered that during olfactory sensory neuron (OSN) development, discrete groups of progenitor/stem cells communicate with each other via a unique Notch/Insm1a signaling module to form neighborhoods of cells that act as hot spots of neurogenesis (generation of new neurons). Retinoic acid signaling from the nearby eye influences this intricate process of new OSN formation, and BDNF (brain-derived neurotrophic factor) signaling helps guide new neurons to their final destinations.
Why should people care about this?
Neurodegenerative disorders are strongly associated with the depletion of neurons across the nervous system. Interestingly, while olfactory sensory neurons (OSNs) are known to be highly regenerative, the loss of smell is often an early indicator of potential neurodegeneration. As a first step to understanding this apparent paradox, we aimed to uncover how new OSNs are generated. Additionally, we hope to discover conserved pathways that might aid neuroregeneration in other organ systems. Finally, our observations of the close coordination and exchange of signals between the nose and the eye shed light on the importance of inter-organ communication for neurogenesis.
How would you explain this to an 8-year-old?
Our noses have tiny nerve cells that detect different kinds of smells that help you enjoy pizza or not enjoy medicine. While zebrafish don’t eat pizza (as far as we know), they have those types of cells, too. Because you can see through zebrafish pretty well, we can put them under a fancy microscope, watch those nerve cells get made, and learn how that happens. What we learn then allows us to think of ways to make new nerve cells that could help people and keep them healthy.
This year brought the return of our image competition with the MBL Embryology course at Woods Hole. Twenty impressive submissions were received from the 2025 class of students, with images ranging from polychaete worms to butterflies, squids and mice. Here, we interview Arthur Boutillon, the Editor’s Choice winner of the image competition with his submission, ‘Embryonic eye of Anole lizard’. As our Editor’s Choice, Arthur’s image was featured on the cover of a recent issue of Development.
7. Embryonic eye of Anole lizard Arthur Boutillon Embryonic eye of Anole lizard stained for nuclei (DAPI, blue) and F-actin (Phalloidin, orange), imaged by spinning disc confocal microscopy and processed using ImageJ.
Can you describe your research career so far?
My research career began during my Bachelor’s studies at the École Normale Supérieure in Paris, France, where I had the opportunity to work with different model organisms through several internships, all focused on morphogenesis.
I then pursued a PhD in Nicolas David’s team at The Laboratory for Optics and Biosciences, École Polytechnique, Palaiseau, France. Working with zebrafish embryos, my favourite model organism so far, I studied the collective movement of cells during gastrulation using a combination of classical approaches (e.g., grafts) and more advanced techniques (e.g., 3D laser ablations), along with extensive live microscopy. We discovered a novel mechanism by which cells coordinate over long distances, a phenomenon we named “guidance by followers”.
Can you tell us about your current research?
After defending my PhD at the end of 2021, I moved to Dresden, Germany, to join Otger Campàs’ group in the Cluster of Excellence Physics of Life as a postdoctoral researcher. Here, I study the mechanics of morphogenesis, still using zebrafish as my model system.
By combining physical measurements, quantitative imaging, and genetic perturbations, I investigate the mechanics of somite boundary formation, work that is currently under revision for publication. I also study the link between signaling and the acquisition of tissue mechanical properties.
Attending the Embryology Course at Woods Hole broadened my perspective on the value of different model organisms. I am now developing research projects centered on mechano-evo-devo to apply for PI positions.
What is your favourite imaging technique/microscope?
Anything that allows me to watch development live!
That said, I have a soft spot for the versatility of point-scanning microscopy.
With our trusted LSM980, I can image both live and fixed samples and perform laser ablation, optogenetics, FRAP, FCS, and more, all on the same instrument!
What are you most excited about in microscopy currently/in the future?
I’m excited about all kinds of new developments: every microscopy technique has its strengths and limitations, and it’s ultimately about finding the best fit for each question. What excites me even more are the tools that help with segmentation and image analysis. I’m constantly amazed by what open-source platforms like StarDist, Cellpose, or Mastodon can achieve.
My dream is to see a unified, open-source platform that integrates these tools seamlessly, something that would save long hours of image analysis after acquisition!
Our September webinar featured three early-career researchers working on gut development. Here, we share the talks from Surojit Sural (Columbia University) and Swarnabh Bhattacharya (Dana-Farber Cancer Institute).
Royal Society Publishing has recently published a special issue of Philosophical Transactions A: Biological fluid dynamics: emerging directions compiled and edited by Smitha Maretvadakethope, Marco Polin, David J Smith and Laurence G Wilson and the articles can be accessed directly at www.bit.ly/TransA2304
A print version is also available at the special price of £40.00 per issue from sales@royalsociety.org
About this issue The microscopic world of algae, bacteria, spermatozoa and other swimming microorganisms is fundamental to life on Earth. Here, fluid dynamics follows very different physical laws from those familiar to us. Friction dominates, so cells have to squirm and corkscrew their way through fluid rather than glide. Microorganism have evolved to survive and thrive in the world of biologically active fluids, performing essential functions such as navigating, feeding, cooperating and reproducing. Long-range interactions in microscopic flow can cause beautiful collective effects, such as pattern formation and ‘active turbulence’. Driven by recent advances and touching on topics ranging from new medical technologies to the origins of life itself, this special issue presents contributions at the cutting edge of research in this field.
(2 votes)
Loading...
(No Ratings Yet)
