New preprint: "On Growth and Form, and Function" with @miltonllera, @MarcelloBarylli, @risi1979, @drmichaellevin Inspired by D'Arcy Thompson's grid transformations, we find that "reusable regulatory handles control phenotypic variation" in NCAs. 🧵 arxiv.org/abs/2609.29755

New #preprint: led by @DrPatrickE, with @HananelHazan @DougHazel @BioelectricCelland many others; @wyssinstitute An important step in our efforts to create tools for the community to accelerate discovery in the field of diverse intelligence as relates to biomedicine and beyond: biorxiv.org/cgi/content/shor… "A platform for automated training of mammalian cell physiology" Controlling cell physiology is difficult, not only because of cells' complexity, but also their capacity for real-time adaptation to interventions, leading to challenges such as drug resistance and transgene silencing. Accumulating evidence suggests that this adaptivity resembles classical forms of learning defined in behavioral science. However, a lack of appropriate platforms has led to gaps in our understanding of cells' capacity for adaptive problem-solving in physiological and transcriptional space. Here, we present a device, the Cell Trainer, capable of performing a wide variety of automated training experiments on non-neural mammalian cells, using timed drug pulses as the stimulus, and a mobile fluorescence microscope to capture images of responses, across replicate cultures. The Cell Trainer can operate in either an open-loop (feedforward) or closed-loop (feedback-controlled) mode, and our image analysis pipeline can report the behaviors of individual cells throughout each experiment and quantify population heterogeneity. We showcase the ability of the Cell Trainer to execute experimental protocols and perform single-cell analyses in both modes. We first demonstrate with a feedforward experiment in which myoblasts are repeatedly pulsed with dimethyl sulfoxide (DMSO) and their discrete calcium responses are analyzed, revealing sensitization-like dynamics. Next, we demonstrate a feedback control scheme wherein the fluorescence of a pH/voltage reporter in kidney cells is maintained below a threshold level with controlled pulses of acid. To accelerate research in the field of cell training, learning, and memory, we are openly sharing the Cell Trainer schematics and software with the research community. This platform provides a flexible tool for studying how cellular physiological states can be shaped by patterned stimulation and feedback control through approaches that work with the native adaptive competencies of cells. A website with how-to-build details etc. coming soon.

New #preprint: @SteffiKapsetaki , Tomer Landsberger biorxiv.org/content/10.64898… When planaria get exposed to barium, their heads explode and fall off. But, remarkably, they quickly grow new heads that are barium-insensitive! How does it work? Out of all the possible targets in their genome, they regulate a small number of genes which enable the heads to live in the K+ channel blocker barium. In our past paper on this (cell.com/iscience/fulltext/S…), we found out which genes, but we had sequenced all the worms as a combined batch - we didn't know if each individual worm finds the same solution in transcriptional space, or different ones. How many solutions to the barium challenge are there? What would you guess - do they all find the same solution or each one walks a different path in transcriptional space, to resolve this stressor? In this new paper, we analyze individual worms: Abstract: "Exposure to the potassium channel blocker barium chloride (BaCl₂) causes head degeneration in Dugesia japonica flatworms, followed by regeneration of BaCl₂-insensitive heads, offering a unique model for studying transcriptional resilience to novel stress. We performed RNA sequencing on individual planaria to investigate different transcriptional solutions to the BaCl₂ challenge, and how regeneration history and social environment shape transcriptomic responses to BaCl₂. We identified a robust transcriptional strategy and a potential sub-strategy for enabling BaCl₂-insensitive head formation. Moreover, we observed pronounced transcriptional differences between untreated worms regenerating from tail fission fragments (tail-regenerated), and untreated full-sized worms that did not fission during the experiment (intact controls), highlighting the lasting impact of regeneration history. Relative to controls, tail-regenerated worms upregulated neurodevelopmental and morphogenetic programs, while downregulating mitochondrial transport and stress-response pathways. Relative to intact controls, BaCl₂-exposed regenerates upregulated ion transport, metabolic, cell cycle, and inflammatory pathways, while downregulating neuronal signaling, ion homeostasis, morphogenesis, and tissue repair programs. Comparison of BaCl₂-exposed isolated and BaCl₂-exposed group-housed worms revealed minimal transcriptional divergence between social conditions. These findings underscore the complex interplay between regeneration, chemical stress, and social context in shaping gene expression."

The film debut of my eyeballs piped.video/J-HDHwEJ2z8?is=lTK7…

Came out!! This work is my first publication from my postdoc at the multicellgenome.com in @IBE_Barcelona. Together with Iñaki Ruiz-Trillo @multicellgenome & Elena Casacuberta to try and ask ourselves what we actually mean by single-cell learning? What mechanisms 1/n

More #preprints: Giving Simulated Cells a Voice: Evolving Prompt-to-Intervention Models for Cellular Control arxiv.org/abs/2505.02766 @namlehai @DrPatrickE @YanboZhang3 @DoctorJosh ZapGPT: Free-form Language Prompting for Simulated Cellular Control arxiv.org/abs/2509.10660 @namlehai @DrPatrickE @YanboZhang3 @DoctorJosh Advancing the Scientific Method with Large Language Models: From Hypothesis to Discovery arxiv.org/abs/2505.16477 @YanboZhang3 @hectorzenil and many others!

It has been a great privilege to work with @drmichaellevin and an amazing team of scientists at @wyssinstitute and @TuftsUniversity to learn how neurons grow and form connections within completely novel bodies! @LaurieONeill99 @mmsperry @LPiolopez @DrPatrickE & Tiffany Lin

Ever wonder what a nervous system would look like if it self-assembled inside a novel being that hadn't faced a history of selection for its organism-level form and function? Or, perhaps you wondered how #Xenobots would look and act, or what their transcriptome would be like, if they had nervous systems? Well, here's the first step: advanced.onlinelibrary.wiley… "Engineered Living Systems With Self-Organizing NeuralNetworks: From Anatomy to Behavior and Gene Expression" Our awesome team: led by @halehf: @LaurieONeill99, @mmsperry, @LPiolopez, @DrPatrickE, and Tiffany Lin. The @TuftsUniversity and @wyssinstitute press releases are here, for summaries: now.tufts.edu/2026/03/16/sci… wyss.harvard.edu/news/toward…

Call for papers for 'Artificial Life for Science and Engineering' We seek work applying ALife concepts and tools to model real-world systems and engineer solutions—and assist scientific discovery through open-ended and curiosity-driven search. Call info: alifeforscience.github.io

test post please ignore teddit.net/r/interesting…

What is the bioelectric pattern of immortality and mortality in hydra? Happy to share our latest work with Angelina Pimkina, @DrPTMcMillen, @parandetayyebi, @DrPatrickE, @drmichaellevin in the journal Bioelectricity! liebertpub.com/doi/10.1089/b… @TuftsUniversity @wyssinstitute

What if you analyzed the transcriptome of a living construct, made of wild-type (genetically-unmodified) cells but that had self-assembled with novel form and function - what genes might such a thing turn on and off, with what relationship to these genes' phylogenetic history, and what modes of control/communication with this form of life would the analysis of novel transcripts enable? I present the hard work of @pai_vaibhav , @LPiolopez, @mmsperry, @DrPatrickE, @parandetayyebi nature.com/articles/s42003-0… Abstract: "Would transcriptomes change if cell collectives acquired a novel morphogenetic and behavioral phenotype in the absence of genomic editing, transgenes, heterologous materials, or drugs? We investigate the effects of morphology and nascent emergent life history on gene expression in the basal (no engineering, no sculpting) form of Xenobots —autonomously motile constructs derived from Xenopus embryo ectodermal cell explants. To investigate gene expression differences between cells in the context of an embryo with those that have been freed from instructive signals and acquired novel lived experiences, we compare transcriptomes of these basal Xenobots with age-matched Xenopus embryos. Basal Xenobots show significantly larger inter-individual gene variability than age-matched embryos, suggesting increased exploration of the transcriptional space. We identify at least 537 (non-epidermal) transcripts uniquely upregulated in these Xenobots. Phylostratigraphy shows a majority of transcriptomic shifts in the basal Xenobots towards evolutionarily ancient transcripts. Pathway analyses indicate transcriptomic shifts in the categories of motility machinery, multicellularity, stress and immune response, metabolism, thanatotranscriptome, and sensory perception of sound and mechanical stimuli. We experimentally confirm that basal Xenobots respond to acoustic stimuli via changes in behavior. Together, these data may have implications for evolution, biomedicine, and synthetic morphoengineering."

Ever wonder what the architecture of a neural network would look like, in a novel organism that had not been through selection for specific structure and function of an embodied nervous system? Here's our #preprint with morphological, behavioral, electrophysiological, and transcriptomic analysis of a new kind of Xenobot with a nervous system: biorxiv.org/content/10.1101/… - the hard work of @halehf @LaurieONeill99 @mmsperry and @LPiolopez Abstract: "A great deal is known about the formation and architecture of biological neural networks in animal models, which have arrived at their current structure-function relationship through evolution by natural selection. Little is known about the development of such structure-function relationships in a scenario where neurons are allowed to grow within evolutionarily-novel, motile bodies. Previous work showed that when a piece of ectodermal tissue is excised from Xenopus embryos and allowed to develop ex vivo, it will develop into a three-dimensional (3D) mucociliary organoid, and exhibits behaviors different from those observed in tadpoles of the same age. These 'biological robots' or 'biobots' are autonomous, self-powered, and able to move through aqueous environments. Here we report a novel type of biobot that is composed of ciliated epidermis and additionally incorporates neural tissue (neurobots). We show that neural precursor cells implanted within the Xenopus skin constructs develop into mature neurons and extend processes towards the outer surface of the bot as well as among each other. These self-organized neurobots show distinct external morphology, generate more complex patterns of spontaneous movements, and are differentially affected by neuroactive drugs compared to their non-neuronal counterparts. Calcium imaging experiments show that neurons within neurobots are indeed active. Transcriptomics analysis of the neurobots reveals increased variability of transcript profiles, expression of a plethora of genes relating to nervous system development and function, a shift toward more ancient genes, and up-regulation of neuronal genes implicated in visual perception."

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