The Beddington Medal is the BSDB’s major commendation to promising young biologists, awarded for the best PhD thesis in Developmental Biology defended in the year previous to the award. Rosa Beddington was one of the greatest talents and inspirational leaders in the field of developmental biology. Rosa made an enormous contribution to the field in general and to the BSDB in particular, so it seemed entirely appropriate that the Society should establish a lasting memorial to her. The design of the medal, mice on a stylised DNA helix, is from artwork by Rosa herself.
We are very pleased to announce the 2021 Beddington Award winner as Kristina Stapornwongkul from the Crick Institute. She completed her PhD with Jean-Paul Vincent as part of the Wellcome Trust funded Developmental and Stem Cell Biology programme. Her work on understanding the mechanisms of diffusion-based signalling gradient formation represents a hugely innovative and original piece of research that will form a bench-mark study in terms of its application of synthetic biology approaches to understand fundamental questions of developmental biology in vivo. During her PhD, Kristina has won multiple prizes and awards, that include best talk prize at the “From Cells to Embryo” meeting in Paris, a selected talk at the “Physics of Living matter meeting” in Marseille, and a poster prize at the “Synthetic Morphogenesis” meeting at EMBL Heidelberg. Her work represents the cutting edge of modern developmental biology in its application of inter-disciplinary approaches.
We’d also like to break convention this year, and highlight our second and third place runner-ups for the award:
2nd place: Can Aztekin (Gurdon Institute/University of Cambridge)
3rd place: Tatiana Solovieva (UCL)
Thanks to all nominees for sharing us synopses of their PhD work. Its safe to say that the future of Developmental Biology is secured.
The central question of her PhD was to ask how effective simple diffusion can be in establishing a morphogen gradient in vivo. She started by asking how effectively GFP can diffuse from a localised stripe source within the wing disk epithelium of drosophila, when fine-tuning the tethering of this protein to extracellular binding partners. This was achieved through the use of surface associated anti-GFP nanobodies to modulate the ligand gradient by trapping the ligand and limiting its leakage. In a bold next step, Kristina then asked whether this engineered gradient would be able to substitute for the endogenous morphogen: Decapentaplegic (Dpp). To engineer the Dpp signalling pathway to be responsive to extracellular GFP, anti-GFP nanobodies were added to Dpp receptors. Strikingly, this was sufficient for GFP to activate phosphorylation of the downstream effectors of the signalling pathway. Such a finding opens up potential for many similar synthetic biology approaches to interrogate the mechanisms of intra-cellular signalling during development. For Kristina, it meant that she could go on to prove the sufficiency of an engineered GFP gradient to appropriately pattern the wing disk in the background of a Dpp loss of function mutant. This response was further improved through the targeted expression of synthetic glypicans, where a low-affinity GFP nanobody was fused to the glycosylphosphatidylinositol (GPI)-anchored components of the ECM. Therefore, the study provided direct proof of the importance of additional ECM binding partners in the modulation of gradient diffusion. Pairing these studies with models developed by the Salbreaux lab, the team were able to better understand how signal receptor, and non-receptor binding interact to tune gradient formation. Therefore, not only does her work provide direct evidence for the sufficiency of morphogen gradients in pattern formation in vivo, it also points the direction towards engineering approaches to generate pattern formation while leaving endogenous signals intact.
The independence and drive of Kristina in the development of her PhD project is clear from reading her nomination letter of JP Vincent:
“It had been shown previously that an inert protein like GFP does not form a gradient on its own in vivo (and this had actually been used as an argument that diffusion could not account for gradient formation). But Kristina argued that this was not a fair test and that gradient formation had to be assessed in the presence of extracellular binders. She realised that recent development (in the availability of anti-GFP nanobodies & in genome engineering expertise) would allow her to design such a test”. JP Vincent
“To create a GFP gradient in vivo is on its own a remarkable achievement but Kristina had the boldness of thinking (and demonstrating) that it could suffice to provide positional information. This came as a shock to me and many developmental biologists and opens the way to further rigorous studies of signalling dynamics in living tissues. Kristina can take most of the credit for the design and execution of her work and for linking up with the physicists, who helped with modelling”. JP Vincent
I’ll leave you with some comments of Kristina herself on her PhD experience:
“First of all, I should say that I have been really lucky with my PhD. I feel that I’ve grown a lot as a scientist in the last years and this is of course all thanks to JP, the Vincent lab and the entire scientific community I was interacting with. I’m incredible grateful to all these people not only for teaching and supporting me but also for making my PhD real fun (especially when the science didn’t work). JP has been a great boss and I am very thankful for his trust and support. He is really fun to work with and I immensely enjoyed the countless hours of discussion we had. We were also lucky to have a very fruitful collaboration with Marc and Luca from Guillaume Salbreux’s lab. I learned so much from them (not only about diffusion). I am also so thankful to the Vincent lab, a great mix of extremely bright and helpful people.”. Kristina Stapornwongkul
Congratulations Kristina on such great achievements during your PhD! The BSDB wish you all the best in the continuation of your scientific career, and are very happy to award you the 2021 Beddington award.
Ben Steventon.
Publications:
K. S. Stapornwongkul and J. P. Vincent, Generation of extracellular morphogen landscapes: The case for diffusion. Nat. Rev. Genetics. Accepted in principle (2021).
K. S. Stapornwongkul, M. de Gennes, L. Cocconi, G. Salbreux, J. P. Vincent, Patterning and Growth Control in vivo by an engineered GFP gradient. Science (80-. ). 370, 321 LP – 327 (2020).
K. S. Stapornwongkul, G. Salbreux, J. P. Vincent, Developmental Biology: Morphogen in a Dish. Curr. Biol. 28, R755–R757 (2018).
P.-M. Martin, R. E. Stanley, A. P. Ross, A. E. Freitas, C. E. Moyer, A. C. Brumback, J. Iafrati, K. S. Stapornwongkul, S. Dominguez, S. Kivimäe, K. A. Mulligan, M. Pirooznia, W. R. McCombie, J. B. Potash, P. P. Zandi, S. M. Purcell, S. J. Sanders, Y. Zuo, V. S. Sohal, B. N. R. Cheyette, DIXDC1 contributes to psychiatric susceptibility by regulating dendritic spine and glutamatergic synapse density via GSK3 and Wnt/β-catenin signaling. Mol. Psychiatry, 1–9 (2016).
