Kyle G Daniels (@ScienceKyle) - Twitter Profili

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🚨What if we could reliably program macrophage polarization state?🚨 biorxiv.org/content/10.648… Macrophages are highly plastic immune cells that perform critical functions by polarizing into distinct cellular states. The polarization state of macrophages can substantially influences the progression of cancers, infections, and autoimmunity. (1/11)

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Kyle G Daniels retweetledi

Polly Fordyce@fordycelab·1h

High-throughput biochemistry enables quantitative characterization of proteins at scale -- but now synthesis of isolated, sequence-validated libraries has become a bottleneck. Check out @MicahOlivas1 & @patrickalmhjell's new preprint to solve this! @Stanford_ChEMH @czbiohub

Micah Olivas@MicahOlivas1

Many experiments in biology happen one protein at a time, which means synthesizing DNA one gene at a time. This is fine for tens of genes. For thousands, the cost is unsustainable. Introducing uSort-M: a method to isolate and sequence-verify thousands of genes at low cost

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Kyle G Daniels@ScienceKyle·7m

@HindRafei Thank you. We’ve also been using the SCR in NK cells, so CISH and (your insights into) CREM have become important!

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Hind Rafei@HindRafei·1h

@ScienceKyle Fantastic!!! Congratulations Kyle and team!! Also the figures are soo beautiful 🤩

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Kyle G Daniels@ScienceKyle·1d

🚨What if we could reliably program macrophage polarization state?🚨 biorxiv.org/content/10.648… Macrophages are highly plastic immune cells that perform critical functions by polarizing into distinct cellular states. The polarization state of macrophages can substantially influences the progression of cancers, infections, and autoimmunity. (1/11)

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Kyle G Daniels@ScienceKyle·2h

@milind_nahiyera We haven’t tried yet. But the SCRs work in T cells, macrophages, NK cells, and HSCs.

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Milind Nahiyera@milind_nahiyera·23h

Neutrophils 🤔🤔🤔

Kyle G Daniels@ScienceKyle

🚨What if we could reliably program macrophage polarization state?🚨 biorxiv.org/content/10.648… Macrophages are highly plastic immune cells that perform critical functions by polarizing into distinct cellular states. The polarization state of macrophages can substantially influences the progression of cancers, infections, and autoimmunity. (1/11)

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Kyle G Daniels@ScienceKyle·2h

@AndrewHouk2 @ScienceJodie @lucasesantanna @Hypothesisfund Thanks. We have an NK cell project that will hopefully wrap up this year.

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unemployed CAR-NK scientist@AndrewHouk2·18h

@ScienceKyle @ScienceJodie @lucasesantanna @Hypothesisfund Cool! Congratulations!

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Kyle G Daniels@ScienceKyle·1d

SCRs containing ‘YLxQ’ motifs (S2 and S3) enhanced phagocytosis of E. coli. We asked if this effect would generalize to enhance phagocytosis of cancer cells by CAR-macrophages. Both in vitro and in vivo, the answer was yes!

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Kyle G Daniels@ScienceKyle·2h

@LouaiLabanieh @JuliaBauman2 Thanks Louai. I hope you’re all settled now!

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Louai Labanieh@LouaiLabanieh·17h

@ScienceKyle @JuliaBauman2 Very cool work! Congrats, Kyle and Team!!

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Kyle G Daniels@ScienceKyle·2h

@maabellanas @LabWaggoner Thanks!

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Miguel Ángel Abellanas@maabellanas·11h

@ScienceKyle @LabWaggoner This is amazing!! Congrats!! 🎉

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Kyle G Daniels@ScienceKyle·2h

@marcora Great question that we haven’t explored yet. We refer only to phagocytosis in the paper because SCRs have similar effects on macrophage engulfment of E. coli and cancer cells (fig. attached) It is possible that SCRs increase efferocytosis, but we need to do more experiments.

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Edoardo Marcora@marcora·2h

What about efferocytic state and DAM?

Kyle G Daniels@ScienceKyle

🚨What if we could reliably program macrophage polarization state?🚨 biorxiv.org/content/10.648… Macrophages are highly plastic immune cells that perform critical functions by polarizing into distinct cellular states. The polarization state of macrophages can substantially influences the progression of cancers, infections, and autoimmunity. (1/11)

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Katie Galloway@GallowayLabMIT·1d

Want the precision and control of RNA devices but not sure how to engineer your lenti to deliver them? 🚨new pre-print from @kaseyslove🚨 hint: syntax matters! 👇

bioRxiv Synthetic Biology@bioRxiv_synbio

Engineering high-titer lentiviral vectors for robust expression of RNA-based gene circuits biorxiv.org/content/10.648… #biorxiv_synbio

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Kyle G Daniels@ScienceKyle·1d

This work was a huge effort led by @ScienceJodie, who was brave enough to take on primary macrophages, with contributions from @lucasesantanna and Tony Salcido-Alcantar, the Bassik and Ramakrishna labs at Stanford. The work was funded by @Hypothesisfund, the Shurl and Kay Curci Foundation, @StanfordCancer, @parkerici, and others.

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Kyle G Daniels@ScienceKyle·1d

This work demonstrates that synthetic signaling domains can program macrophages, serving both as a platform to understand macrophage biology and as a tool to fine-tune phenotypes for therapeutic applications. We welcome feedback, so please email us if you’d like to share your thoughts or work with the system.

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Kyle G Daniels@ScienceKyle·1d

We recombined 9 different motifs to generate a wide spectrum of synthetic macrophage polarization states which differed in polarization markers like CD163, CD206, CD40, CD80, PDL1, and the capacity to phagocytose E. coli.

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Kyle G Daniels@ScienceKyle·1d

SCRs containing motifs from natural cytokine receptors were sufficient to polarize macrophages. For example, the 'YDKPH' motif (S1) from the IFNγ receptor mimicked IFNγ stimulation, while the 'YLRQ' motif (S3) from the IL-10 receptor mimicked IL-10 stimulation.

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Kyle G Daniels@ScienceKyle·1d

We used a synthetic cytokine receptor (SCR) platform to activate unique signaling programs in human primary macrophages in a cytokine-independent manner (see the platform’s debut in T cells biorxiv.org/content/10.110…). The signaling is programmed by varying motifs on the receptor’s intracellular domain.

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UChicago Pritzker Molecular Engineering@UChicagoPME·2d

A new grant from @Biohub will help @UChicagoPME Asst. Prof. @DrMilosSimic advance research aimed at detecting neurodegenerative diseases like Alzheimer’s and Parkinson’s decades before cognitive decline appears. 🔗 Read more: ms.spr.ly/6018vu52y #Biohub #UChicago #Alzheimers #Parkinsons

UChicago Pritzker Molecular Engineering tweet media

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Kyle G Daniels

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