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Профиль

Benjamin Swedlund

Профиль Vively

Postdoc in the Morsut lab at USC trying to understand and engineer pattern self-organisation using synthetic gene circuits. SynBio, Dev Bio & Stem Cells. Passionate about science, music, gymnastics, and nature.

100% support @openrxiv.bsky.social in their mindset to allow 3rd party services to test new ways to assess preprints. Its just a shame the direction qed took as we’re not looking for « one metric to rule them all » but a collection of transparent, dissociated indicators of quality and impact

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I understand the need for simple metrics because of the volume of piblications and job applicants - but the issue with IF and journals was already lack of transparency and bias. We cannot expect AI to do any better for neither.

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I would argue that for the first cutoff, however, IF and journal name are still impactful - whether consciously or not, I wouln’t be surprised if when reading CVs, most researchers automatically apply an implied « impact » depending on where the applicant has published

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A novelty of our approach is the orthogonality of the engineered circuits: since they are synthetic, they do not interfere with the cell’s own signalling systems and can even act independently from one another. This means we can design more complex circuits - see these cool encoded dual patterns.3/4

Supplemental movie 4Timelapse imaging of L929 mouse fibroblasts containing dual, orthogonal synthetic reaction-diffusion circuits. Both circuits are composed of synNotch-mediated juxtacrine activation combined with parac...vimeo.com
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In our case, model and experiments were perfectly aligned: all it takes to form self-organised multicellular patterns is a two-component synthetic reaction-diffusion circuit, composed of a membrane-bound self-activating activator and a secreted inhibitor. 2/4

Supplemental movie 22-dimensional simulation of a juxtacrine activator-paracrine inhibitor (JAPI) reaction-diffusion circuit architecture, parametrised to recapitulate the phenotype of an equivalent synthetic circuit bui...vimeo.com
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Agreed! Although since as default, we humans are on the lazy side (consider having to go through a pile of 300 applications), shortcut metrics will always be needed… but they should be community-driven, transparent, fair, and certainly not manipulated as IF is by for-profit journals

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Thank you Zainab 🥳☺️

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Thanks Nikolas! 🕺

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Huge thank you to @leonardomorsut.bsky.social, all co-authors, past and present lab members who made this possible. More to come, stay tuned! (9/9)

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More broadly, this work adds to growing evidence that reaction-diffusion-mediated patterning may not require diffusion per se, but rather controllable spatial movement. What if we generalized this concept to… reaction-movement (or something similar that sounds more sexy)? (8/9)

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My biggest take-aways: simple two-component circuits are sufficient to self-organize multicellular patterns in mammalian systems. And these compact designs can be built on to produce more complex, multi-state spatial patterns. We hope to use them to perturb and control endogenous patterning. (7/9)

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Since this worked so well, I wondered: why restrict ourselves to simple spots and stripes? Thus, we experimentally explored the design space of dual interacting patterning circuits, producing a rich morphospace of gorgeous, two-colour multicellular spatial patterns. (6/9)

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Experimentally, we show that synNotch-based synthetic implementations of this novel circuit architecture work beautifully in mammalian cells. Although the resulting patterns are irregular rather than perfectly periodic, we can accurately model them and tune their spatial properties. (5/9)

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Our solution: completely change how the activator moves. Instead of passively diffusing, what if it was membrane-tethered and propagated through cell-cell contact relay? Mathematically, this is quite different from diffusion - yet this substitution still supports pattern self-organization. (4/9)

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Reaction-diffusion circuits can generate self-organized spatial patterns from just two interacting components, a short-range activator and a long-range inhibitor. But their synthetic reconstruction faces a major challenge: the activator must diffuse much slower than the inhibitor. (3/9)

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It all started when we contributed to a review on self-organized patterning, and I thought: wait - in theory, you can do so much with such small circuits? If that’s the case, why not try to reconstruct them using synthetic biology tools to control tissue patterning? (2/9)

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What are fairer ways to judge research without relying on flawed proxies like journal brand or impact factor?Leonardo points to NIH-style grant application panel discussions as a model. Could scientific societies adopt a similar approach to review articles or evaluate preprints? 6/6

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Peers evaluation remains a cornerstone of scientific research. But the current format of peer-review is ungrateful and opaque. Leonardo's approach to peer-review is straightforward: does the author's data match their claims? If not, it is up to them to change their claims or generate more data. 5/6

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One disadvantage is in case of patent applications, where public disclosure needs to be carefully times. For career progression in academia, preprints seem to be taken into account, although university policies regarding their consideration for hiring and promoting faculty are often unclear. 4/6

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