iiinova — where your digital self keeps evolving

Erik Poppleton @poppleton.phd · 22/09/2026

In addition to complexing well with LNPs, the origami also survive intact for up to 60 days at fridge temperatures in PBS! What you're going to have to read the paper to find out more about are the immunological outcomes of structuring the mRNA. There's a lot more than fits in a thread!

Encapsulation and stability of mRNA origami
a. schematic of encapsulation efficiency measurements. Free RNA and encapsulated RNA are measured via dye accessibility before and after LNP dissociation.
b. Results of encapsulation efficiency. Commercial mRNA is about 35% encapsulated, while folded mRNA origami is over 90% encapsulated.
c. Transfection over time. All RNAs tested lasted 60 days at fridge temperatures in PBS
d-e. AFM imaging and gels of origami at day 0 and day 60 of fridge storage showing the structures remain well-folded.

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Erik Poppleton @poppleton.phd · 22/09/2026

Lots of purification and controls later to ensure that we transfected fully-structured RNA, we were able to show that cells will express this highly-structured mRNA, albeit at a much lower level than unstructured controls. This appears to be a structurally-mediated, and not activation of the ISR.

$Expression of mRNA origami a. Schematic of introduction to cells and ribosome profiling setup. b-c. Fluorescence of EGFP encoded in origami structures via flow cytometry and microscopy. d-3. Polysome profiling results showing that while commercial mRNA is almost entirely associated with the polysome fraction, the highly structured origami seems to show a lot of stalled monosomes, in addition to actively translating polysomes.$

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Erik Poppleton @poppleton.phd · 22/09/2026

Why do this? LNP-delivered mRNA (e.g vaccines) have a loading problem, you don't get many mRNAs per particle. We wondered if we could deliver more by compacting the mRNA into an origami. It works! The mRNA-origami fold into monodisperse rectangles and encapsulate much better than commercial mRNA.

Scientific schematic of mRNA-origami. Panels:
a-c schematics showing how by programming self-assembly into the thermodynamically-favored base pairing, we can go from a floppy, unstructured sequence, to a compact rectangular sequence.
d. Schematic of the construct showing that the coding sequence and the 'structuring sequence' are statically separated in the origami
e. MD simulation of the resulting structure
f-g. close-up and zoomed out AFM images showing well-formed rectangular RNA origami
h. Gell analysis of folding yields.

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Erik Poppleton @poppleton.phd · 11/05/2026

There is only one song powerful enough to make an entire generation start singing with just a single note. (Blank video, sound up)

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Erik Poppleton @poppleton.phd · 10/05/2026

I feel like @aptshadow.bsky.social was binging on Creature posts from @lize.bsky.social while writing the Bug Section of Children of Strife.

Highlight of text from Children of Strife by Adrian Tchaikovsky

"This is a good batch," Pil said approvingly. He picked out one specimen with the drone cams. It must have been over a mètre long, with legs twice that-just ridiculously unwieldy legs. It thrashed through the slick foliage as though trying to swim. Its head-or the front end of it, as it didn't have a distinct head section-was studded with clusters of eyes, and half a dozen weaving antennae. These fondled everything in front of it suggestively every time it stopped.
Kott looked at it and wondered why it didn't just die of utter horror at its own existence. But, however ill, malformed and generally wrong every generation of bugs down there looked, she couldn't deny them their zest for their horrible, misshapen life.

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Erik Poppleton @poppleton.phd · 02/04/2026

I will never get Mambo no. 6 out of my head

Tweet from @corylockwood saying “Someday Lou Bega's gonna drop
Mambo number 6 and I hope it kills every single one of us.”

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Erik Poppleton @poppleton.phd · 01/04/2026

I ran over 50 µs of molecular dynamics simulations to characterize the dynamics and geometric constraints introduced by the triplexes! Simulations revealed that there is a tradeoff between occupancy in the three triplex sites, and that generally not all of them can be satisfied at the same time.

Analysis of simulation data showing the occupancy of each of the triplex motifs and how it correlates with the angle between the joined helices. Generally, peaks in the triplet probabilities for each triplet corresponds to a discrete peak in the angle distribution.

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Erik Poppleton @poppleton.phd · 01/04/2026

And it works! AFM imaging of αKL-containing tiles shows assembly of unbounded stacks of tiles mediated by the loops! We tested 4 different sequence variants based on different biological 23S rRNA sequences and a negative control where U nucleotides replaced the triplex-forming purines.

A gallery of AFM images showing how changing the sequence of the flanking bases affects yields of nanoscale tile assemblies mediated by ails. Changing the A-minor bases to Gs maintains high yields of structures, and any base can be inserted as a spacer between the 4-base loop and the A-minor triplex. Disrupting triplexes by inserting Us leads to poor yield. Additionally, yield of assemblies is dependent on multiple aKLs, revealing the cooperatively of multiple, weak interactions.

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Erik Poppleton @poppleton.phd · 01/04/2026

"But that looks so easy!" you say. "Just design a few unpaired bases!" Not so fast! Those bases must be pre-organized into a loop without disrupting the host helix. Thankfully, lead author and RNA wizard Cody Geary developed a nature-inspired triplex strategy which satisfies all the requirements. 🧬

Motif composition of the aKL: Most of the motif is based on the alphaPK from the 23S rRNA subunit, which has a single A-minor triplet and a three-base loop. Cody extended that motif with a motif based on the P4-P6 Group 1 Intron structure from Tetrahymena, which stabilizes a crossover with a G-major and two A-minor triplets. By extending the loop by 1 additional base and modifying the flanking sequences, we generated the aKL, which should be a 4-base loop stabilized by neighboring triplexes.

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Erik Poppleton @poppleton.phd · 01/04/2026

Why do we need new motifs? The structure of nucleic acids limits the ways molecular designers can connect helices! When routing a single stranded origami, there's no good way to make sideways connections. The αKL solves this problem by looping out a 4-base sequence, which joins helices side-by-side.

The library of existing single-stranded connectors. 180-degree and 120-degree kissing loops connect two strands loop-to-loop. Branched kissing loops can branch a third strand from a 180-degree kissing loop at a 90-degree angle, but that forces any connections away from the connection because the bKL sequence needs to be long enough to be stable. Paranemic crossovers (PX) can be used to connect helices side-by-side, however they require complete crossover of the strand. The aKL joins neighboring helices by a short loop producing from the side of the helix.

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Erik Poppleton @poppleton.phd · 01/04/2026

In addition to carrying genetic data, DNA and RNA can also be designed to fold into 'molecular breadboards' with nanometer addressability. To enable tightly-packed RNA origami, we developed a new motif, the αKL, which we're excited to share in our preprint!🧬🧪 1/🧵 www.biorxiv.org/content/10.6...

Scientific diagram showing the alphaKL. Left panels shows various atomic force microscope images of structures built using the motif, while the right panel shows a computer rendering of the motif.

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Erik Poppleton @poppleton.phd · 06/02/2026

The plot thickens in the sponges-vs-ctenophores-as-animal-outgroup drama…

Screenshot of a Science Magazine headline announcing the retraction of “Integrative phylogenetic positions sponges at the root of the animal tree”

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Erik Poppleton @poppleton.phd · 28/12/2025

Is the AotY list mostly the big melodeath releases from this year? Yeah, call me basic. Was it a good year for melodeath? Also yes. Can’t get the texture of the guitar on the Amorphis album out of my head. #metalSky #AotY2025

Top-12 album list:

Återstod - ÅTERSTOD + Meißel split
Amorphis - Borderland
Blackbraid - Blackbraid III

Shadow of Intent - Imperium Delirium
Allegaeon - The Ossuary Lens The Halo Effect - March Of The Unheard

Grief Ritual - Collapse
Aephanemer - Utopie
Lorna Shore - I Feel The Everblack Festering Within Me

Rivers of Nihil - Rivers of Nihil
Eluveitie - Anv
Unreqvited - A Pathway to the Moon

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Erik Poppleton @poppleton.phd · 02/12/2025

98% is apparently a very wide percentile in the distribution…

Duolingo year in review showing 36537 XP is also 98%

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Erik Poppleton @poppleton.phd · 20/11/2025

I think I’m gonna have to retract this meme I made… 🧬

Strong doge vs weak doge meme where the strong is labeled DNA saying “still readable after being in a dead mammoth for 1.6 million years” and the weak labeled RNA saying “oh no! Is that a hydroxide ion?”

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Erik Poppleton @poppleton.phd · 28/10/2025

I recently pushed an update to the #oxDNA to PDB converter which makes the backmapped structures work out-of-the-box with all-atom simulation tools (the previous version didn't correctly remove the phosphate from the 5' end). Here's a 2-minute demo on how to prepare an oxDNA structure for GROMACS! 🧬

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Erik Poppleton @poppleton.phd · 17/09/2025

Why does this keep happening??

Screenshot of a Bluesky post containing a screenshot of a Reddit post saying “The Hatman does NOT respect gender pronouns past 450mg” in a quote post of Melania Trump looming in a hat.

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Erik Poppleton @poppleton.phd · 01/08/2025

This is just... not true? His thesis was on sequences which resemble miRNA in the HIV genome which affect CD4 expression. It's an impressive thesis, especially from a globetrotting rockstar. But neither it, nor the associated paper is highly cited, let alone by anything to do with vaccines. 🧪

Screenshot from Google Scholar showing Bryan "Dexter" Holland's publications. The paper has been cited 34 times and the thesis 4 times.

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Erik Poppleton @poppleton.phd · 15/06/2025

It should be obvious from the title, but the first 30 pages introduced baroque styles with some historical tales, some deeper cuts from Escher’s catalogue, and the historical/mathematical context of Gödel’s Incompleteness Theorem. Then dropped some AI musings which are still relevant today.

Page 26 from GEB which reads in part:
“By the early 1950's, mechanized intelligence seemed a mere stone's throw away; and yet, for each barrier crossed, there always cropped up some new barrier to the actual creation of a genuine thinking machine. Was there some deep reason for this goal's mysterious recession?
No one knows where the borderline between non-intelligent behavior and intelligent behavior lies; in fact, to suggest that a sharp borderline exists is probably silly. But essential abilities for intelligence are certainly:
to respond to situations very flexibly; to take advantage of fortuitous circumstances;
to make sense out of ambiguous or contradictory messages; to recognize the relative importance of different elements of a
situation;
to find similarities between situations despite differences which
may separate them;
to draw distinctions between situations despite similarities which
may link them;
to synthesize new concepts by taking old concepts and putting
them together in new ways;
to come up with ideas which are novel.
Here one runs up against a seeming paradox. Computers by their very nature are the most inflexible, desireless, rule-following of beasts. Fast though they may be, they are nonetheless the epitome of unconsciousness.
How, then, can intelligent behavior be programmed? Isn't this the most blatant of contradictions in terms? One of the major theses of this book is that it is not a contradiction at all. One of the major purposes of this book is to urge each reader to confront the apparent contradiction head on, to savor it, to turn it over, to take it apart, to wallow in it, so that in the end the reader might emerge with new insights into the seemingly unbreachable gulf between the formal and the informal, the animate and the inanimate, the flexible and the inflexible.”

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Erik Poppleton @poppleton.phd · 03/05/2025

They really hid it in Fig S28-i… looks like a 500-minute doubling time, compared with 200-minute for the parent strain. Also much lower maximum OD600. 🧪

A plot showing growth of the first version of Syn57, which is essentially a flat line (“near unculturable in liquid), vs the second version which has a 500 minute doubling time and saturates around 0.6 OD600.

A plot which contains the growth curve of the parent strain which has about a 200 minute doubling time and a maximum OD600 around 1.4

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Erik Poppleton @poppleton.phd · 24/02/2025

Wow, this one from @cnn.com might be the worst political graphic I’ve ever seen. 1. Party colors are very important in German politics (they often just call CDU “blacks”). You can’t just choose random colors. 2. “22.6% Others” hides two of the big stories: the collapse of FDP and the gains by Linke.

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Erik Poppleton @poppleton.phd · 11/02/2025

I bow down to the great Bossett. But also, can anybody explain why Echidna+Quasar had such a low score?? I tried googling the combination but got nothing.

The result of a word association game where you try to get as far apart as possible the words used were Ontology, Camisole, Carburetor, Echidna, Quasi, Melancholy, and Coriander. This gave a score of 94.31 which was higher than 99.92% of people.

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Erik Poppleton @poppleton.phd · 01/02/2025

I think I figured out why California can’t build its high-speed rail system! New ETA: 2070

A screenshot from Wikipedia saying:
“The California High-Speed Rail Authority's (CHSRA) board approved on 15 November 2017 an early train operator contract with DB Engineering & Consulting USA.[9] The firm is the U.S. arm of Deutsche Bahn AG. As early train operator, DB Engineering & Consulting will assist CHSRA with planning, designing and implementing the state's high-speed rail program.”

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Erik Poppleton @poppleton.phd · 24/01/2025

We made the oxView export so we could 3D print structures. The Molecular Nodes visualization is going to be much more flexible as far as blender styling and is also able to load trajectories. Here are some tiny resin prints of Holliday junctions I made for an outreach project.

Tiny resin 3D prints of Holliday junctions, an X-shaped structure made of helical DNA molecules

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Erik Poppleton @poppleton.phd · 31/12/2024

This was the year where things I wasn’t expecting absolutely blew me away and much of what I was excited for was meh (except Time II, that slapped). Here’s to more surprises in 2025! #metalsky #metalsky2024 #AOTY

The Body & Dis Fig - Orchards of a Futile Heaven

The album cover shows a mushroom-shaped cloud of fireballs raining from the sky.

Linkin Park - From Zero

The album cover is an abstract image of pinks and grays that looks like an oil slick.

Dvne - Voidkind

The album art shows a giant figure clad in red robes with gold filigree, with another figure in white which is also an opening in the chest of the larger figure. A crowd of people enter the smaller figure and there are far too many arms.

Thy Shining Curse - Theurgia

The art shows two hooded, metal-faced figures facing each other holding skulls.

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Erik Poppleton @poppleton.phd · 02/12/2024

Assuming that unpaired scaffolds are actually unpaired is a poor assumption! This is the same conclusion we came to in the Leaf-Spring Nanoengine paper, where a part of the spring, designed to be single-stranded, formed hairpins which stabilized the closed state. 🧬 www.nature.com/articles/s41...

Screenshot of text from a scientific paper:
Dynamic reconfiguration was then explored for 2D and 3D voxel shapes (Fig. 4). Similarly to monomers (Fig. 2E), intramonomer interfaces on “vertex” voxels were switched between flexible and rigid states by addition of invader or connector strands. The length of the ssDNA scaffold tether was found to affect yields of possible monomer geometries (fig. S45). The 354-nt tether has a theoretical maximum ssDNA contour length of ~240 nm, but in oxDNA simulations, the tether was predicted to have secondary structure (fig. S10). Experimentally, structures with tether spacings of 7 to 33 nm formed with high yields (Ndesigns = 7, 79 to 89%; figs. S137 and S138). Yields were lower for the 62-nm tether spacing but recovered after addition of short complementary strands to remove secondary structure from the scaffold, increasing the range of possible structural reconfigurations (fig. S46).

The part about oxDNA simulations predicting secondary structure is highlighted.

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Erik Poppleton @poppleton.phd · 02/12/2024

I finally got around to reading this and Fig 3e is so cute! 🧬

A part of a figure from a scientific paper showing a design schematic for a dinosaur assembled from 'DNA origami voxels'. The dinosaur was then functionalized with flourophores and imaged with DNA-PAINT, resulting in a super-resolution microscope image of blue dots outlining a very small dinosaur.

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Erik Poppleton @poppleton.phd · 23/11/2024

I’m not sure how you would make this more obvious, but this article is a letter to the editor, not a case report or review. Seeing lots of people saying this displays the rot of scientific publishing, and while publishing is rotten to the core, this isn’t it. 🧪

A screenshot of the issue table of contents for a surgery journal including “Practice of neurosurgery on Saturn” under the “Correspondence” header, not under “Case Reports” or “Reviews”

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Erik Poppleton @poppleton.phd · 17/11/2024

This tidbit is amazing! I love these examples where computers start behaving more like biology instead of rigid logic machines. Also there’s a typo at the top of page 3 in the description of MD, idk if it’s too late to fix for typesetting.

A screenshot of text from the paper describing a mysterious optimization where the code was made 1% faster by copying a memory write and then never accessing it again.

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Erik Poppleton @poppleton.phd · 12/11/2024

The Nature cover for those who haven't seen it

The Cover of the March 2006 issue of Nature highlighting the article introducing DNA origami. The cover image shows how a smiley face drawn as a bunch of tubes rastering back and forth becomes an almost perfect AFM image of the design implemented in self-assembled DNA.

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Erik Poppleton @poppleton.phd · 11/11/2024

I'm over 2 years late doing this, but somebody recently pointed out to me that I never updated the PyPi repository to say that oxDNA Analysis Tools was merged into the oxDNA repository. If you're still using the PyPi version, make sure you update to the new source! 🧬

Screenshot of the PyPi page for oxDNA Analysis Tools which now says that it was merged with the main oxDNA repository in July 2022.

(I'm using this post to test a custom feed builder, it's not that important)

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Erik Poppleton @poppleton.phd · 10/11/2024

From the Wikipedia article on Brazil’s electricity grid, it’s almost all hydro. Pleasantly surprised to see wind and solar in the next two slots too! en.m.wikipedia.org/wiki/Electri...

A pie chart and line graph showing Brazil’s electricity generation. In 2023 hydro power made up 47.8% of the generating capacity followed by solar (15.5) and wind (12.0)

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Erik Poppleton @poppleton.phd · 03/11/2024

Another, similar paper provided a fantastic euphemism for “killed by volcano” in science speak. (Some guts too). www.science.org/doi/10.1126/...

A screenshot of a Science article with this text highlighted:
“Upon entry into shallow
marine waters, the ash flow would have formed a turbid cloud, leading to complications for respiration, locomotion, and digestion. The digestive system of Protolenus (Hupeolenus) sp. is infilled by material of the same composition as the surrounding matrix, suggesting that
this individual may have accidentally ingested water-suspended ash prior to death. Smothering by ash would have also hindered mobility”

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Erik Poppleton @poppleton.phd · 18/10/2024

I chose pumpkin as my medium for the Japanese spider crab day of #invertober2024!

A Japanese spider crab carved into a pumpkin lot by a candle inside

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Erik Poppleton @poppleton.phd · 17/10/2024

Attention new Bsky users: as the butterfly site, you’re legally required to quote this skeet with an original bug pic you took yourself! (don’t forget the alt text)

A black and orange butterfly poses on a club of flower buds against a background of foliage. The light passing through the wings makes it appear to glow.

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Erik Poppleton @poppleton.phd · 07/10/2024

Does it matter…? Hmmm, let’s check Project 2025… And this doesn’t even begin to cover the social effects that Trump’s presence has on science and the international perception of the US as a place that’s good to work.

Page from project 2025 calling for breaking up and privatizing NOAA.

Page from Project 2025 calling for splitting up the NIH into state-level entities and criticizing NIH investigations into sexual assault and funding research into gender-affirming care.

Page from Project 2025 calling to an end to all international aid regarding climate change. Further denies that climate change has material impact on people’s lives in developing countries.

Page from Project 2025 calling for banning all applied research at the National Labs and criticizing the use of NSF funding for technology transitions to a cleaner economy.

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Erik Poppleton @poppleton.phd · 06/10/2024

My contribution to days 2-6 of #Invertober2024! I haven’t drawn in years and this is so much fun!

An ink drawing of an malachite butterfly

An ink drawing of a common cuddlefish over a crowd of grasping tentacles

A page containing both two fried egg jellyfish and a greater bee fly. The first jellyfish has too many lines and looks too flat compared with the second.

An ink drawing of a Mexican redknee tarantula

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Erik Poppleton @poppleton.phd · 01/10/2024

Anybody else getting permission denied errors when you try to get a BibTeX citation through Google Scholar? Seems to be happening to my colleagues as well... 🧪

Google error showing permission denied for a Google Scholar BibTeX URL

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Erik Poppleton @poppleton.phd · 24/09/2024

Here, as a demonstration of this I asked Dall-E 3 to draw a hand, and it does fine. It has seen a bunch of images labeled "hand". But then if I ask it to draw an image of a gymnast doing pommel horse, the guy has 4 fingers on one hand and the other is in a silly place.

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Erik Poppleton @poppleton.phd · 16/09/2024

I was an early refugee from Science Twitter and arrived to find the posters had gotten here before us. Those early months were…strange…exciting…and filled with that smell of new possibilities (or maybe that was just Alf).

Bluesky 10 million users celebration card showing number 85878

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Erik Poppleton @poppleton.phd · 15/09/2024

And then there’s this 15th century painting in the National Gallery of London where the artist seems to have gone out of his way to pose the horses in such a way as to show their nards (particularly the second panel).

A busy two-panel painting showing the story of David and Goliath which has lots of horses. A suspicious number of horses are turned towards the viewer such that you can see their nards.

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Erik Poppleton @poppleton.phd · 14/09/2024

I had to look up J. Robert Latham and his campaign website background is a really weird closeup of hands. #utpol

White text of libertarian policy positions on ending government involvement in family law over a background which is an extreme closeup of hands.

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Erik Poppleton @poppleton.phd · 13/09/2024

On today’s episode of the Molpigs Podcast we’re (re)introducing the team! This one is more meta than our usual researcher interviews and might be interesting to early career researchers in other fields as well! (Especially if you first conference is coming up) 🧪 Links to all feeds: podcast.molpi.gs

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Erik Poppleton @poppleton.phd · 13/09/2024

The power of Brazilian social media can be summed up in a Spotify search for “Come to Brazil”.

A screenshot of a Spotify search for “Come to Brazil” revealing numerous songs with exactly that title. The one by The Offspring is highlighted as currently playing.

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Erik Poppleton @poppleton.phd · 26/08/2024

A fine outbreak of Eriogaster arbusculae (Alpen-Wollafter) high in the French Alps #inverteFest

A bundle of black caterpillars with white spots and hairs cluster on orange foliage. One particularly large individual has orange spots in addition to white.

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Erik Poppleton @poppleton.phd · 12/08/2024

One of these days I’m going to stop panicking at the drugstore and buying *almost*, but not quite, the right thing. These are tabs for cleaning your dishwasher, not tabs for cleaning your plates. (Previous hits have been conditioner instead of shampoo and body lotion instead of face lotion)

A brightly-colored and friendly package with German text containing four things which look like dishwasher tabs, but upon actually reading the package are in fact tabs for cleaning your dishwasher.

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Erik Poppleton @poppleton.phd · 03/08/2024

Friends? Friends that you should not hug.

A tan butterfly with orange and black spots perches on the lid of a water bottle.

A mauve stinger jellyfish floats near the surface of water which has the texture of blown glass.

A honeybee crawls out of a trumpet vine flower

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Erik Poppleton @poppleton.phd · 05/07/2024

Even having a PhD in RNA research, I really enjoyed this wander through the history of the field with one of the greats. So many chance encounters and brazen jumps into the unknown required for breakthroughs. Also wild how the entire field essentially came from a few highly productive labs.

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