Every human face is unique, allowing us to distinguish between individuals. We know little about how facial features are encoded in our DNA, but we may be able to learn more about how our faces develop by looking at our ancient relatives, the Neanderthals. Neanderthal faces were quite distinctive from our own, with large noses, pronounced brows and a robust lower jaw. Now, scientists from the MRC Human Genetics Unit in the Institute of Genetics and Cancer at the University of Edinburgh, UK, are using the DNA of our extinct distant relatives to learn more about how faces develop and evolve. Published today in the journal Development, they show how a region of Neanderthal DNA is better at activating a jaw-forming gene than the human counterpart, revealing one potential reason for Neanderthal’s larger lower jaws.
Hannah Long (University of Edinburgh, UK), who led the study, explains that scientists have sequenced the Neanderthal genome using DNA extracted from ancient bone and says, “The Neanderthal genome is 99.7% identical to the genome of modern-day humans and the differences between species are likely responsible for altering appearance”. Both human and Neanderthal genomes consist of about 3 billion letters that code for proteins and regulate how genes are used in the cell, which makes finding regions that impact appearance like looking for a needle in a haystack. Fortunately, Long and her colleagues had an informed idea where to look first: a region of the genome that is linked to Pierre Robin sequence, a syndrome in which the lower jaw is disproportionately small. “Some individuals with Pierre Robin sequence have large deletions or DNA rearrangements in this part of the genome that change face development and limit jaw formation. We predicted that smaller differences in the DNA might have more subtle effects on face shape,” said Long.
By comparing human and Neanderthal genomes, the team found that in this region, roughly 3000 letters in length, there were just three single-letter differences between the species. Although this region of DNA doesn’t contain any genes, it regulates how and when a gene is activated, specifically a gene called SOX9, a key coordinator of the process of face development. To demonstrate that these Neanderthal-specific differences are important for the development of the face, Long and colleagues needed to show that the Neanderthal region could activate genes in the right cells at the right time as the embryo develops. The researchers simultaneously inserted the Neanderthal and human versions of the region into the DNA of zebrafish and programmed the zebrafish cells to produce different colours of fluorescent protein depending on whether the human or Neanderthal region was active. Watching the zebrafish embryos develop, the researchers found that both the human and Neanderthal regions were active in the zebrafish cells that are involved in forming the lower jaw and the Neanderthal region was more active than the human version.
A 2-day-old zebrafish embryo viewed from below; with the zebrafish head pointing towards the top-left corner of the image. Within the transparent embryo, the fluorescent cells show activity of the inserted human DNA in specific cells (lower green signal) overlapping with the developing jaw (lower purple signal). Image credit: Kirsty Uttley and Hannah Jüllig.
“It was very exciting when we first observed activity in the developing zebrafish face in a specific cell population close to the developing jaw, and even more so when we observed that the Neanderthal-specific differences could change its activity in development,” said Long. “This led us to think about what the consequences of these differences could be, and how to explore these experimentally.” Knowing that the Neanderthal sequence was more powerful at activating genes, Long and colleagues then asked if the resulting increased activity of its target, SOX9, might change the shape and function of the adult jaw. To test this theory, they provided the zebrafish embryos with extra SOX9 and found that cells that contribute to forming the jaw occupied a larger area.
“In our lab, we are interested in exploring the impact of additional DNA sequence differences, using a technique that mimics aspects of facial development in a dish. We hope this will inform our understanding of sequence changes in people with facial conditions and inform diagnosis,” says Long. This research shows that by studying extinct species we can learn how our own DNA contributes to face variation, development and evolution.
Uttley, K., Jüllig, H. J., De Angelis, C., Auer, J. M. T., Ozga, E., Bengani, H. and Long, H. K. (2025). Neanderthal-derived variants increase SOX9 enhancer activity in craniofacial progenitors that shape jaw development. Development, 152, dev204779. doi:10.1242/dev.204779
Last September marked the return of our image competition with the MBL Embryology course at Woods Hole. The 2025 cohort submitted impressive images, ranging from polychaete worms to butterflies, squid, and mice, using a range of microscopy techniques. Here, we interview Nicole Roos and Anthony Wokasch, the winners of the popular vote of the image competition with their submission, ‘Mouse embryo’. As winners of the image competition, their submission was featured on the cover of a recent issue of Development.
Can you describe your research career so far?
Nicole: As a kid I loved conducting at-home experiments, visiting the science museum and attending my chemistry and biology classes, so pursuing a career in science has always been a no brainer for me. I started my research career as a freshman at The University of Texas at Dallas, USA, while pursuing my BSc in Biochemistry. Inspired by a family member who survived breast cancer, I joined the lab of Dr Nikki Delk to study chronic inflammation in tumor microenvironments. My interest in genetics was sparked while investigating mutations that affect chromatin remodeler function at the University of Texas Southwestern Medical Center, USA, with Dr Laura Banaszynski. Now, I am a fourth year PhD candidate working with Dr Leila Rieder in the Genetics and Molecular Biology program at Emory University, USA.
Anthony: I began my research career at American University, USA, where I completed a joint BSc/MSc in Biology. During my time there, I did my Master’s thesis in the lab of Naden Krogan, where I characterized the role of the floral boundary gene SUPERMAN (SUP) in a transcriptional mechanism which regulates gene expression and floral organ patterning of the reproductive organs in the flower of Arabidopsis thaliana. Following completion of my Master’s, I became a fellow at the National Cancer Institute (NCI) in the lab of Dr Peter D. Aplan. There I tested the effects of a DNA methyltransferase (DNMT1) inhibitor in a murine model for Myelodysplastic Syndrome (MDS). However, at this point my interest in development was overwhelming and led me to pursue a PhD at Vanderbilt University, USA, where I am a PhD candidate in my fourth year.
Can you tell us about your current research?
Nicole: At Emory, I use the powerful model system Drosophila melanogaster (fruit flies) to study how histone genes, which encode proteins that package and organize DNA in the nucleus, are regulated in embryogenesis and throughout development. Histone gene regulation is uniquely regulated throughout development, and this regulation is carried out by a nuclear body called the histone locus body. Not only do I get to study genetics, but through my research I took interest in developmental biology. This compelled me to apply to the Embryology course offered by the Marine Biological Laboratory (MBL) in Woods Hole, USA, where I discovered a strong desire to study regeneration and/or evolutionary developmental biology in the future.
Anthony: My current research, under the guidance of Dr Maureen Gannon focuses on how the Pdx1 transcription factor and its C-terminal interacting factors, Oc1 and SPOP, regulate the choice between proliferation or differentiation of early pancreatic progenitor cells. This work has deepened my understanding of how epigenetic and molecular factors control cell fate decisions during organogenesis.
What is your favourite imaging technique/microscope?
Nicole: The majority of my research at Emory University requires widefield fluorescence microscopy, so I was excited to take the Embryology Course at the MBL to learn various confocal microscopy techniques. I quickly became fascinated with live imaging using various spinning disc confocal microscopes (my favorite being the Nikon Yokogawa W1 spinning disc) and collaborated with other students to live image processes such as sea urchin egg and sea star sperm cross-fertilization (sea sturchins), nematode egg laying, and early embryonic cleavage of comb jellies. However, I also loved taking intricate fluorescence images on the Evident FV400 scanning confocal, the same microscope we used to take the image of the stained mouse embryo.
Anthony: My favorite microscope is the Evident FV4000 Confocal Laser Scanning Microscope, which we used at the MBL during the course to take this is image.
What are you most excited about in microscopy?
Nicole: I’m fascinated by current microscopy techniques which bypass diffraction limit imaging and visualize single molecule interactions. The development of expansion microscopy techniques alongside super resolution microscopy allow scientists to visualize cell biology more deeply now than ever before. I am especially intrigued by the combination of expansion microscopy with stimulated electron depletion (STED), which has been used in fluorescence imaging of chromatin at the nucleosomal level. This can inform the field of developmental biology and my field, where we study DNA-protein interactions to understand how histones are regulated.
Anthony: I am really excited right now doing whole-mount immunofluorescence of embryonic mouse pancreas samples and using confocal microscopy and or light-sheet (LSFM) to reveal key changes of cell fate choices and morphology during development.
Our October webinar featured two early-career researchers working on development across scales. Here, we share the talks from Osvaldo Contreras (Victor Chang Cardiac Research Institute and UNSW) and Yinan Wan (Biozentrum, University of Basel).
[Editorial from Development’s latest Special Issue – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues, edited by Merixtell Huch and Mansi Srivastava.]
Traditionally, developmental biology has been considered the study of the embryo, and significant events such as metamorphosis or birth signify the pinnacle of development. However, we now better appreciate that development is a continuum and that – as in plants – developmental processes occur throughout the lifetime of an animal. Cell fate specification and differentiation, morphogenesis and patterning can continue after embryonic development; growth, degrowth, ageing, regeneration, and even reverse development (e.g. in some disease states) are just some examples of development-like processes occurring during the life history of a species. This special issue sought to draw these connections and to highlight how embryonic studies have revealed fundamental lifelong principles, advocating for a broader interpretation of developmental biology that circumvents restriction to specific stages in the life cycle.
The 26 research and review-type papers published in this issue illustrate this goal, including a breadth of mechanisms, research organisms and organ types. A selection of Research Articles demonstrates how several tissues and organs continue to develop, differentiate and mature during post-embryonic stages, establishing the principle of lifelong development. These examples include the mouse gut (Pan et al., 2025) and adipose tissue (Mahapatra et al., 2025), zebrafish vasculature (Preußner et al., 2025), and the Caenorhabditis elegans germline (Gupta et al., 2025). The mammalian nervous system represents a particularly well-studied example of postnatal refinement in response to sensory stimuli and learning. Therefore, we are glad to capture studies that discuss the ongoing development of retinal cells (Shah et al., 2025) and visual cortex (Xavier et al., 2025), microglia (Hammond et al., 2025), astrocytes (Iyer et al., 2025) and neurons (Liu et al., 2025). In addition to an extension of embryonic development, some tissues and organs undergo extensive remodelling during metamorphosis in invertebrates or puberty in humans (Rauner et al., 2025), and tissue-resident stem cells are crucial for the homeostasis and maintenance of adult tissues, which may also change behaviour over a lifespan due to shifting niche environments (Puri and Blanc, 2025).
Beyond these examples of post-embryonic development, regeneration offers perhaps the most striking illustration of development-like processes occurring in adults. We are therefore excited that regenerative studies are well represented in the special issue. Research papers characterise the initial molecular events and signalling in regeneration (Quinn et al., 2025), as well as the regeneration of specific tissues and organs, such as the zebrafish skin (Craig et al., 2025) and heart (Feng et al., 2025; Forman-Rubinsky et al., 2025). Whole-body regeneration is also explored in planarians, with studies revealing how these species maintain robust regenerative potential throughout life (Zelko et al., 2025), and the mechanisms by which polarity and patterning are re-established during regeneration (Anderson and Petersen, 2025; Miliard et al., 2025). In addition, our review-type content highlights a recent workshop from this field (Bayin et al., 2025), the interplay between vertebrate regeneration and the nervous system (Wakelin and Johnston, 2025; Tendolkar and Mokalled, 2025) and non-traditional model systems with remarkable regenerative potential (García-Arrarás et al., 2025). We are pleased that one of these organisms, the tapeworm, also features in a Research Article in the same issue (Nanista et al., 2025). Moreover, our Techniques and Resources articles provide valuable references for studying adult stages of highly plastic species (Temiz et al., 2025; Little et al., 2025), with a Hypothesis article exploring such phenotypic plasticity as the basis of complex developmental potential (Dardiry and Ikmi, 2025).
This special issue underscores the continuity of developmental processes across the lifespan from embryogenesis to regeneration, tissue maintenance and phenotypic plasticity. By linking classical developmental biology and emerging insights into post-embryonic and adult stages, we aim to broaden the field’s conceptual understanding of developmental biology. We hope you enjoy reading the issue and that it inspires further investigation of how developmental mechanisms operate beyond early life, adapt to environmental cues, and contribute to lifelong organismal plasticity. Development welcomes future submissions that explore these dynamic and evolving aspects of development across diverse systems and life stages.
Spotted a preprint in this list that you love? If you’re keen to gain some science writing experience and be part of a friendly, diverse and international community, consider joining preLights and writing a preprint highlight article.
Yuan-Chen Tsai, Hajime Ozaki, Xinyi Wang, Axel A. Almet, Isabel Fleming, Kaori Shiraiwa, Matthew Jung Min Noh, Caihao Nie, Sunnyana Trejo, Bret Kiyoshi Sugita, Jiya Dalal, Ruben Alberto Gonzalez, Briana De Jesus, Gregory Li-Min Chen, Michael J Gandal, Qing Nie, Momoko Watanabe
Wilke H. M. Meijer, Virginia Andrade, Suzan Stelloo, Wouter M. Thomas, Marek J. van Oostrom, Eveline F. Ilcken, Kim T. J. Peters, Michiel Vermeulen, Katharina F. Sonnen
Rachel A. Minerath, Rajesh K. Kasam, Casey O. Swoboda, Vikram Prasad, Kelly M. Grimes, N. Scott Blair, Hadi Khalil, Christina M Alfieri, Logan Eads, Anthony J. Saviola, Mohamad Azhar, Lianjie Miao, Mingfu Wu, Michelle Tallquist, Kirk C. Hansen, Matthew T Weirauch, Katherine E. Yutzey, Douglas P. Millay, Jeffery D. Molkentin
Márta Korbonits, Xian Wang, Sayka Barry, Chung Thong Lim, Oniz Suleyman, Stefano De Tito, Nazia Uddin, Maria Lillina Vignola, Charlotte Hall, Laura Perna, J. Paul Chapple, Gabor Czibik, Sian M Henson, Valle Morales, Katiuscia Bianchi, Viðar Örn Eðvarðsson, Kristján Ari Ragnarsson, Viktoría Eir Kristinsdóttir, Anne Debeer, Yoeri Sleyp, Rena Zinchenko, Glenn Anderson, Michael Duchen, Kritarth Singh, Chih Yao Chung, Yu Yuan, Sandip Patel, Artem O. Borovikov, Hans Tómas Björnsson, Hilde Van Esch, Sharon Tooze, Ezra Aksoy, Caroline Brennan, Oliver Haworth
Zukai Liu, Chengxiang Qiu, Connor A. Kubo, Stella Xu, Riza M. Daza, Eva Nichols, Wei Yang, Anh Vo, Mary B. O’Neill, Choli Lee, Jay Shendure, Nobuhiko Hamazaki
Kaleb Hill, Aaron H. Griffing, Michael A. Palmer, Bezia Lemma, Aria Lupo, Tony Gamble, Natalia A. Shylo, Andrej Košmrlj, Paul A. Trainor, Celeste M. Nelson
Olga D. Jarosińska, Amalia Riga, Hala Zahreddine Fahs, Joren M. Woeltjes, Ruben Schmidt, Fathima S. Refai, Suma Gopinadhan, Kristin C. Gunsalus, Mike Boxem
Sarah N. Steiner, Eric Horst, Mitre Athaiya, Craig N. Johnson, Joseph Y. Shen, Michelle L. Kerns, Geeta Mehta, Ramiro Iglesias-Bartolome, Pierre A. Coulombe
Akshai Janardhana Kurup, Aya Mikdache, Patricia Diabangouaya, Gwendoline Gros, Camila Garcia-Baudino, Cristian A. Undurraga, Andres F. Sarrazin, Pedro P. Hernandez
Rafael Casado-Navarro, Ana Bermejo-Santos, Rodrigo Torrillas-de la Cal, María Pilar Madrigal, Virgilia Olivé, Li Ying Chen-Chen, Sonia Amorós-Bru, Sandra Jurado, Esther Serrano-Saiz
Judhajeet Ray, Evelyn Jagoda, Maya U. Sheth, James Galante, Dulguun Amgalan, Andreas R. Gschwind, Chad J. Munger, Jacob Huang, Glen Munson, Madeleine Murphy, Eugenio Mattei, Timothy Barry, Vasundhara Singh, Aarthee Baskaran, Helen Kang, Eugene Katsevich, Lars M. Steinmetz, Jesse M. Engreitz
Ye Lynne Kim, Young-Woo Jo, Takwon Yoo, Kyusang Yoo, Ji-Hoon Kim, Myungsun Park, In-Wook Song, Hyun Kim, Yea-Eun Kim, Sang-Hyeon Hann, Jong-Eun Park, Daehyun Baek, Young-Yun Kong
Michael C. Mazzola, Ting Zhao, Anna Kiem, Trine A. Kristiansen, Karin Gustafsson, Lai Ping Wong, Emily Scott-Solomon, Marissa D. Fahlberg, Sarah Forward, Emane Rose Assita, Giulia Schiroli, Maris Handley, Youmna Kfoury, Tsuyoshi Fukushima, Samuel Keyes, Azeem Sharda, Jelena Milosevic, Hiroki Kato, Pavel Ivanov, David B. Sykes, Sheldon J. J. Kwok, Ruslan I Sadreyev, Vijay G. Sankaran, Ya-Chieh Hsu, David T. Scadden
Octavia Santis Larrain, Alice Alhaj Kadour, Sobhika Agarwala, Wantong Li, Bradley W. Blaser, Michael R. Lasarev, Roxana Alexandridis, Anthony Veltri, Khaliun Enkhbayar, Elliott J. Hagedorn, Owen J. Tamplin
Katharina Lemberg, Gijs A.C. Franken, Korbinian M. Riedhammer, Selina Hölzel, Kirollos Yousef, Kraisoon Lomjansook, Gina Kalkar, Caroline M. Kolvenbach, Daniel Marchuk, Elena Zion, Ken Saida, Florian Buerger, Friedhelm Hildebrandt
Declan J. Gainer, Kassandra M. Coyle, Matthew T. Rätsep, Douglas Quilty, Brian Tran, Sofia Skebo, M. Martin VandenBroek, Kimberly L. Laverty, Yupu Deng, Shawyon P. Shirazi, Hugh JM Brady, Jennifer M.S. Sucre, Eric Vivier, Niraj Shrestha, Hing C. Wong, Duncan J Stewart, Nicolle J. Dominik, Mark L. Ormiston
Wentao Han, Hassan Bjeije, Hamza Celik, Michael Rettig, Nancy Issa, Andrew L. Young, Yanan Li, Infencia Xavier Raj, Christine R. Zhang, Aishwarya Krishnan, Tyler M. Parsons, Samantha C. Burkart, Jason Arand, Wei Yang, Jeffrey A. Magee, Grant A. Challen
Michelle Lohbihler, Amos A. Lim, Stéphane Massé, Maggie Kwan, Omar Mourad, Olya Mastikhina, Brandon M. Murareanu, Malak Elbatarny, Renu Sarao, Beiping Qiang, Wahiba Dhahri, Matthew L. Chang, Alice L.Y. Xu, Amine Mazine, Shahryar Khattak, Sara S. Nunes, Kumaraswamy Nanthakumar, Michael A. Laflamme, Stephanie Protze
Cory P. Johnson, Hannah M. Somers, Sophie E. Craig, Heath Fuqua, Lynne Beverly-Staggs, Kailee E. Tanaka, Sydney M. Brown, Charles H. Toulmin, Matthew D. Cox, Joel H. Graber, Melissa S. Maginnis, Hermann Haller
Giorgio Anselmi, Vincent Frontera, Christina Rode, Andrew Jarratt, Naeema T. Mehmood, Matthew Nicholls, Stella Antoniou, Emanuele Azzoni, John Stamatoyannopoulos, Ditsa Levanon, Yoram Groner, Marella F.T.R. de Bruijn
İsmail Küçükaylak, Francisco Javier Martínez Morcillo, Kai Halwas, Nils Reiche, Manuel Metzger, Petra Comelli, Jürgen Brinckmann, Sabine Eming, Matthias Hammerschmidt
Meryam Beniazza, Masahito Yoshihara, Daniel F Kaemena, James Ashmore, Suling Zhao, Michael O’Dwyer, Emil Andersson, Victor Olariu, Shintaro Katayama, Abdenour Soufi, Kosuke Yusa, Keisuke Kaji
Yuancheng Ryan Lu, James C. Cameron, Yan Hu, Han Shen, Shintaro Shirahama, Alexander Tyshkovskiy, Zhaoyi Chen, Jiahe Ai, Daniel Y. Zhu, Margarete M. Karg, Lindsey A. Chew, George W. Bell, Siddhartha G. Jena, Yue He, Philip Seifert, Daisy Y. Shu, Mohamed A. EI-Brolosy, Qiannuo Lou, Bohan Zhang, Anna M. Puszynska, Xiaojie Qiu, Xiao Tian, Meredith Gregory-Ksander, Vadim N. Gladyshev, David A. Sinclair, Magali Saint-Geniez, Jason D. Buenrostro, Catherine Bowes Rickman, Bruce R. Ksander, Jonathan S. Weissman
Tom Levy, Chiara Anselmi, Katherine J. Ishizuka, Tal Gordon, Yotam Voskoboynik, Erin McGeever, Angela M. Detweiler, Liron Levin, Karla J. Palmeri, Daniel Dan Liu, Rahul Sinha, Benjamin F. Ohene-Gambill, Tal Raveh, Maurizio Morri, Virginia Vanni, Lucia Manni, Debashis Sahoo, Norma F. Neff, Benyamin Rosental, Irving L. Weissman, Ayelet Voskoboynik
Julia Schwarzpaul, Clara M. Droell, Afsheen Kumar, Harishny Sarma, Madeleine Gruenauer, Selen Z. Ucar, Julio C. Hechavarría, Andreas G. Chiocchetti, Denise Haslinger
Ioanna Peraki, Ioannis K. Deligiannis, Dimitris Botskaris, Marianna Stagaki, Haroula Kontaki, Elena Deligianni, Giannis Giannoulakis, Matthieu D. Lavigne, Celia P. Martinez-Jimenez, Iannis Talianidis
Eva-Sophie Wallner, Natalie Edelbacher, Liam Dolan
Supergene control of chiral development in mirror-image flowers Haoran Xue, Marco Saltini, Nicola Illing, Kelly Shepherd, Olivia Page-Macdonald, Oliver Marketos, Caroline Robertson, Anand Shankar, Sarah Süß, Christian Kappel, Saleh Alseekh, Eva E. Deinum, Robert A. Ingle, Michael Lenhard
Sjoerd Woudenberg, Andrew R.G. Plackett, Zhaodong Hao, Hidemasa Suzuki, Luis Alonso Baez, Cecilia Borassi, Thorsten Hamann, Minako Ueda, Jane A. Langdale, Joris Sprakel, Jasper van der Gucht, Dolf Weijers
Gabriele Panicucci, Vinay Shukla, Viktoriia Voloboeva, Leonardo Jo, Kees van Kollenburg, Sara Buti, Laura Dalle Carbonare, Francesco Licausi, Daan A. Weits
Bonnie K. Kircher, Antonia Weberling, Erin J. Vance, Natalia A. Shylo, Katherine Starr, Zoe B. Griffin, Hannah Wilson, Melainia McClain, Florian Hollfelder, Suzannah A. Williams, Thomas J. Sanger, Richard R. Behringer, Paul A. Trainor
Axel H Newton, Ella R Farley, Andrew T Major, Jennifer C Hutchison, Ben M Lawrence, Karen E Sears, Marilyn B Renfree, Aiden M C Couzens, Geoff Shaw, Sara Ord, Richard A Schneider, Andrew J Pask
Jasmine D. Alqassar, Teomie S. Rivera-Miranda, Joseph J. Hanly, Christopher R. Day, Silvia M. Planas Soto-Navarro, Paul B. Frandsen, Riccardo Papa, Arnaud Martin
Atsushi Saito, Stephanie Tankou, Kazuhiro Ishii, Makiko Sakao-Suzuki, Edwin C. Oh, Hannah Murdoch, Ho Namkung, Sunday Adelakun, Keiko Furukori, Masahiro Fujimuro, Paolo Salomoni, Gerd G. Maul, Gary S. Hayward, Qiyi Tang, Robert H. Yolken, Miles D. Houslay, Nicholas Katsanis, Isao Kosugi, Kun Yang, Atsushi Kamiya, Koko Ishizuka, Akira Sawa
Gonzalo Herranz, Diego Alonso-Larre, Tamara González, Laura Akintche, Alejandra Ramos-Manzano, Marta Iborra-Pernichi, María Velasco de la Esperanza, Covadonga Díaz-Díaz, Ian G Ganley, Patricia Boya, Sara Cogliati, Nuria Martínez-Martín, Fernando Martín-Belmonte
Daniel A. Reed, Anna E. Howell, Nadia Kuepper, Alice M. H. Tran, Astrid Magenau, Deborah S. Barkauskas, Max Nobis, Cecilia R. Chambers, Victoria Lee, Lily M. Channon, Jessie Zhu, Shona Ritchie, Janett Stoehr, Kaitlin Wylie, Julia Chen, Denise Attwater, Kate Harvey, Sunny Z. Wu, Kate Saw, Ruth J. Lyons, Anaiis Zaratzian, Michael Tayao, Andrew Da Silva, David Gallego-Ortega, Anthony J. Gill, Thomas R. Cox, Brooke A. Pereira, Kendelle J. Murphy, Jennifer P. Morton, Elgene Lim, Alexander Swarbrick, Sandra O’Toole, Michael S. Samuel, C. Elizabeth Caldon, Alexandra Zanin-Zhorov, Paul Timpson, David Herrmann
Rianne G. Bouma, Willem-Jan de Leeuw, Aru Z. Wang, Muddassir Malik, Joeke G.C. Stolwijk, Veronique A.L. Konijn, Anne Mensink, Natalie Proost, Maarten K. Nijen Twilhaar, Tibor van Welsem, Negisa Seyed Toutounchi, Alsya J. Affandi, Jip T. van Dinter, Fred van Leeuwen, Joke M.M. den Haan
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Kiara C. Eldred, Matthew Wooten, Derek H. Janssens, Joshua Hahn, Shane J Neph, Sierra J. Edgerton, Gracious Wyatt-Draher, Stephanie M. Sherman, Jane E. Ranchalis, Andrew B. Stergachis, Thomas A. Reh, Steven Henikoff
Ryan G. Savill, Alba Villaronga-Luque, Marc Trani Bustos, Yonit Maroudas-Sacks, Julia Batki, Alexander Meissner, Allyson Q. Ryan, Carl D. Modes, Otger Campàs, Jesse V Veenvliet
Namwook Kim, Christine S. Kim, Junhee Park, Hyeon Jun Yoon, Ju Ang Kim, Yong Gun Kim, Joonhyung Kim, Injun Song, Donghyuck Ahn, Jihyeon Myeong, Byungmoo Oh, Jaeyoon You, Eunju Hong, Sukin Jeong, Kyungmoo Yea, Sung Won Kim, Ok Sarah Shin, Seung Joon Kim, Minho Lee, Myungin Baek, Youngtae Jeong
Jingyu Wang, Danail Stoychev, Mick Phillips, David Miguel Susano Pinto, Richard M. Parton, Nick Hall, Josh Titlow, Ana Rita Faria, Matthew Wincott, Dalia Gala, Andreas Gerondopoulos, Niloufer Irani, Ian Dobbie, Lothar Schermelleh, Martin Booth, Ilan Davis
Amine Mazine, Alexander A. Mikryukov, Ian Fernandes, Clifford Z. Liu, Soheil Jahangiri, Marcy Martin, Eric K. N. Gähwiler, Melanie Generali, Juliana Gomez, Neda Latifi, Yifei Miao, Yu Liu, Michael A Laflamme, Craig A Simmons, Simon P. Hoerstrup, Maximilian Y. Emmert, Bruce D. Gelb, Mingxia Gu, Gordon M. Keller
Lucien Hinderling, Hannah S. Heil, Alfredo Rates, Philipp Seidel, Manuel Gunkel, Benedict Diederich, Thomas Guilbert, Rémy Torro, Otmane Bouchareb, Claire Demeautis, Célia Martin, Scott Brooks, Evangelos Sisamakis, Erwan Grandgirard, Jerome Mutterer, Harrison Oatman, Jared Toettcher, Andrii Rogov, Nelda Antonovaite, Karl Johansson, Johannes K. Ahnlinde, Oscar André, Philip Nordenfelt, Pontus Nordenfelt, Claudia Pfander, Jürgen Reymann, Talley Lambert, Marco R. Cosenza, Jan O. Korbel, Rainer Pepperkok, Lukas C. Kapitein, Olivier Pertz, Nils Norlin, Aliaksandr Halavatyi, Rafael Camacho
Jack Nunn, Håkon da Silva Hyldmo, Lauren McKnight, Heather McCulloch, Jennifer Lavers, Julie Old, Laura Smith, Nicola Grobler, Cheryl Tan Kay Yin, Wing Yan Chan, Candice Raeburn, Nittya S. M. Simard, Adam Kingsley Smith, Sam Van Holsbeeck, Eleanor Drinkwater, Kit Prendergast, Emma Burrows, Christopher L. Lawson
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
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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.
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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
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