Molpigs
@molpigs.bsky.social
160 followers 29 following 52 posts
We are the MOLecular Programming Interest Group, early-career researchers in the field of molecular programming building our community through podcasts, reading groups and community activities. Links to all podcast feeds and Slack at molpi.gs
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molpigs.bsky.social
We've organized two reading groups on classic papers in molecular programming:
- A celebration of the late Ned Seeman, the founder of DNA nanotechnology
- Foundations of DNA computing

Let's talk about some of the great papers we've read! Each discussion will start as a quote of this post. 🧬
molpigs.bsky.social
Thank you for joining us! We look forward to your report on whether it's easier to teach an immunologist DNA origami or a molecular programmer immunology!
molpigs.bsky.social
Podcast drop🧬! As part of the Molecular Programming Flightplan, we assembled a panel discussion on collaboration! The panel is now available as two podcasts, each with half the panel, and a bonus interview with @programmablematter.bsky.social.

Links to all major feeds here:
podcast.molpi.gs
Reposted by Molpigs
floppleton.bsky.social
Molecular Programmers🧬: @programmablematter.bsky.social summons us to organize a “Flightplan”, a 10-year strategic initiative for the field. The meeting will be July 21-23rd in Seattle and will be moderated by NSF program officers. Travel funding is available!

Apply here: mpflightplan.com/apply-now
Apply now! — MP Decadal Flightplan
mpflightplan.com
molpigs.bsky.social
Follow WONDER for networking opportunities and upcoming mentorship events aimed at increasing female representation and retention in the Molecular Programming field 🧬
wonder-dna.bsky.social
Hello (bluesky) world!
We are WONDER 🧬, an organization aimed at female PhD students, early and late career researchers within DNA Nanotechnology and related fields 😊🧬

Follow us here to stay updated and sign up to our mailing list (link in bio) to never miss out on any news🧬
molpigs.bsky.social
Thank you to everybody who came to our 🧬DNA origami🧬 reading group over the last 7 weeks! We all learned a ton from the discussions and revisiting these classic papers.

What should our next topic be?? Leave us a comment to help us decide.
molpigs.bsky.social
It's time for the finale of the 🧬DNA origami🧬 reading group! This week we're thinking about how to make origami biiiiiig. When previous papers assembled multiple origami, the yield started to crash. This week's paper is an attempt to get around that problem.

www.nature.com/articles/s41...
molpigs.bsky.social
This week in the Molpigs 🧬DNA Origami🧬 Reading Group there are two cool concepts we're exploring: dynamic structures, and using blunt-end stacking as a structural tool instead of treating it as The Enemy. Info on how to join the discussion in the quoted thread!

www.science.org/doi/full/10....
molpigs.bsky.social
This week in the Molpigs 🧬DNA Origami🧬 Reading Group, we're exploring how DNA origami went from tightly packed sheets/blocks, to open wireframes with complex and beautiful geometries. This paper required designing intricate strand routing, let's follow the path!

www.nature.com/articles/nna...
molpigs.bsky.social
Welcome to the halfway point in the 🧬DNA origami🧬 reading group! This week we're reading "Folding DNA into Twisted and Curved Nanoscale Shapes", the second 2009 paper from the Shih lab demonstrating the programmability of DNA origami.

www.science.org/doi/full/10....
molpigs.bsky.social
For week three of our 🧬DNA origami🧬 reading group we're reading the first of two 2009 papers from the Shih lab which demonstrated that you really could fold DNA into any 3D shape! This paper also demonstrated Cadnano, which remains the most used design software today.

www.nature.com/articles/nat...
molpigs.bsky.social
The second meeting of the Origami Reading Group is tonight at 18:00 EST! Come discuss the original DNA Origami with us (spoiler, it’s shockingly sassy). 🧬
molpigs.bsky.social
It's time to put the origami in our DNA Origami Reading Group! This week we're reading Rothemund's "Folding DNA to create nanoscale shapes and patterns" to understand this seminal paper in context! What did Rothemund know, and what did he intuit? Join us to discuss!🧬

www.nature.com/articles/nat...
molpigs.bsky.social
First 🧬DNA Origami reading group🧬 meets today! Our first paper is a precursor to origami, where Yan and colleagues showed that you could build larger structures via scaffolded tile assembly!

www.pnas.org/doi/10.1073/...
molpigs.bsky.social
Excited to start our 🧬DNA origami🧬 reading group next week! We’ll be hosting two weekly sessions:
Tuesday @ 20:15 CET
Thursday @ 18 EST

You can still sign up by joining the reading-group channel on Slack or filling the form for email updates!

Timezone converter:
molpi.gs/timezones#tz...
molpigs.bsky.social
It's time for another Molpigs reading group! This time we'll be routing our brains through the history of DNA origami. We will be starting the week of March 10th and reading 1 paper/week for 7 weeks. Please fill out either the form linked in the next post or join the Molpigs Slack for updates. 🧬🧬🧬
molpigs.bsky.social
And that's the story. Extremely nerdy, not particularly flashy, but this little cube was one of the first demonstrations that there is, in fact, Plenty of Room at the Bottom if you have the ingenuity to get matter to self-assemble for you! 8/8
molpigs.bsky.social
Behold! the final gel! Building the cube up and tearing it down. Lane 4 contains the purified cube. That's cool. Lanes 5-11 are various restriction digests of the cube, which show that it breaks down in ways consistent with it having been a cube with 6 knotted faces in the first place. 7/8
The gel showing assembly and disassembly of the cube.  The important lane is lane 4, which shows a single, high-weight band corresponding to the assembled and purified cube.  Lanes 5-11 are then various restriction enzyme digestions, resulting in either 3, 2 or 1 interlocked DNA circles depending on which sides of the cube are cut by the enzymes.
molpigs.bsky.social
They could prove ligation with exonuclease digestion! Two things in this busy gel:
1. Lane 4 losing the top band meant the cube should be 10 bases-per-side, not 11. This wasn't obvious as DNA has a periodicity of 10.5 bp.
2. Lane 2 keeping the top band from lane 1 means ligation was a success! 6/8
The gel demonstrating successful ligation of the triple-catenene.  Each lane shows many bands containing sub-products, but what's important is the topmost band in each lane, corresponding to the fully-formed triple catenene.  Lanes 1 and 3 are the assembled catenene with 10 and 11 base-pairs per side, respectively.  Lanes 2 and 4 show the same structures after digestion with an exonuclease which will remove any un-ligated strands.  In lane 2, the top band is still present showing successful ligation, while in lane 4, it's gone, showing that for some reason the 11-base loops will not close.
molpigs.bsky.social
Here's the assembly gel where they add 5 strands to their first, circularized strand and then ligate the two halves of the cube together to get an open 'belt'. However they ran into an aggregation problem in the 6th step, which is why they did the purify-and-reconstitute step from figure 1. 5/8
Figure 2 from the paper showing stepwise assembly of the "belt" structure which can be ligated into the cube. Addition of each strand leads to a slightly higher band on the gel, until you ligate two of the 5-strand complexes together, at which point a faint target band appears and a huge aggregate stuck in the well.
molpigs.bsky.social
For modern molecular programmers, ligating the strands looks strange. We almost never do that today! But that was the secret sauce that let them prove they had synthesized a cube with just gels. You see, the ligated DNA strands resulted in knots, which don't fall apart on a denaturing gel. 4/8
molpigs.bsky.social
But keep in mind! This was a crystallography lab borrowing equipment from the neighboring biochemistry lab, doing something never done before. They didn't have any of the fancy equipment that we take for granted today. No AFM, let alone a CryoEM. So how could they prove they had a cube?? 3/8
molpigs.bsky.social
Here's the plan: starting with 10 linear, synthetic DNA strands, Ned's team annealed strands onto a growing belt with intermediate ligation steps, resulting in a final structure which has 6 strands, each one corresponding to one face of the cube 2/8
Figure 1 from the paper showing how you can add strands in a stepwise manner to create a cube, first creating two opposite faces separately with overhangs which can be ligated to form a "belt", then the belt can be purified into three interlocked rings, reconstituted with its strands, and then those can be ligated again to form a cube.
molpigs.bsky.social
In this series on the origins of DNA nanotechnology, we've so far seen a lot of DNA, not a lot of nanostructure and not a lot of technology. Today's paper introduces structure, we're looking at the first well-defined object built out of DNA, the humble cube! 🧬 1/8
www.nature.com/articles/350...