Nicholas Southern
@neuroscinikolai.bsky.social
740 followers 1.8K following 23 posts
PhD Student @ https://niopeklab.de/ Engineering switchable proteins💡 Views and opinions are my own 🇺🇸 in 🇩🇪
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neuroscinikolai.bsky.social
Excited to share my main PhD work is finally out! 🥳

We built a phage-assisted evolution platform to evolve allosteric protein switches (POGO-PANCE) and introduce cumulative, targeted mutations/Indels (RAMPhaGE)!

See how we evolved ultra-strong, light-switchable AraC variants 🌚🌞
neuroscinikolai.bsky.social
Since it’s binding based, it makes sense you can delete these regions but it is neat that you dont majorly affect positioning using the typical sgRNA length, though circular permutation might yield different results overall. Thanks for the detailed insights, and best of luck with your submission! 😄
neuroscinikolai.bsky.social
Also its so interesting seeing how robust these proteins are to large scale deletions like this, as you would imagine the spacing of the domains themselves to one another would greatly impact your ability to truncate them. Did you guys also consider playing w/ sgRNA content like in the OG paper? 😄
neuroscinikolai.bsky.social
Hahaha also although you can’t edit, you can at least delete posts here as I am sure people on my feed noticed as I was writing on my preprint with the same typo 5 times in a row 🤦
neuroscinikolai.bsky.social
Thanks for the full response Andrew! I suppose it makes sense you’re mostly optimising for ease/time here although you still need to order the sgRNA libraries. As for small deletions, I certainly agree but I also imagine having connective residues could help string deleted junctions together
Reposted by Nicholas Southern
martinowk.bsky.social
In the early years of my PhD I remember being asked if we'd ever treat or cure diseases like HIV or Huntington's. I remember saying maybe, but not knowing if I believed. Seeing research pay off as real impact on human lives is - incredible.

www.bbc.com/news/article...

www.bbc.com/news/article...
Huntington's disease successfully treated for first time
One of the most devastating diseases finally has a treatment that can slow its progression and transform lives, tearful doctors tell BBC.
www.bbc.com
Reposted by Nicholas Southern
jorg-vogel-lab.bsky.social
Looking for a new approach to studying or eliminating phages? Check out our study introducing anti-phage ASOs (antisense oligos) out in @Nature today. nature.com/articles/s4158…
neuroscinikolai.bsky.social
You know I liked this paper, but I was more curious why they went this route for library construction versus trying to improve their earlier MISER strategy given that recombineering efficiency has seen some advances since. Maybe someone @savagecatsonly.bsky.social can help me 😄
neuroscinikolai.bsky.social
I’ll eventually get caught up, but I listen while pipetting so there’s a lot of “day science” to get through first (right now on recording 21 with Daniel Kahneman 😅😂)
neuroscinikolai.bsky.social
Been having a lot of fun lately listening to the Night Science Podcast after stumbling on it from the article series by @itaiyanai.bsky.social and Martin Lercher, definitely recommend it if you have a passing interest in the creative aspects of how the scientific process is conducted 😄
neuroscinikolai.bsky.social
Really interesting and impressive work!!!
Reposted by Nicholas Southern
soreklab.bsky.social
Preprint: De-novo design of proteins that inhibit bacterial defenses

Our approach allows silencing defense systems of choice. We show how this approach enables programming of “untransformable” bacteria, and how it can enhance phage therapy applications

Congrats Jeremy Garb!
tinyurl.com/Syttt
🧵
Synthetically designed anti-defense proteins overcome barriers to bacterial transformation and phage infection
Bacterial defense systems present considerable barriers to both phage infection and plasmid transformation. These systems target mobile genetic elements, limiting the efficacy of bacteriophage-based t...
www.biorxiv.org
Reposted by Nicholas Southern
biorxiv-synthbio.bsky.social
Growth, dissolution and segregation of genetically encoded RNA droplets by ribozyme catalysis https://www.biorxiv.org/content/10.1101/2025.08.29.673008v1
Reposted by Nicholas Southern
martinpacesa.bsky.social
Exciting to see our protein binder design pipeline BindCraft published in its final form in @Nature ! This has been an amazing collaborative effort with Lennart, Christian, @sokrypton.org, Bruno and many other amazing lab members and collaborators.

www.nature.com/articles/s41...
Reposted by Nicholas Southern
skiles.blue
A terrorist targeted federal workers last week. There wasn’t much reporting on it. But I’m not finished thinking about it! 🧵

An anti-vaxxer fired more than 500 gunshots into CDC Atlanta, shattering 150 “blast-proof” windows on 6 buildings. Employees were pinned down in terror.
Reposted by Nicholas Southern
biorxiv-biophys.bsky.social
De novo design of light-regulated dynamic proteins using deep learning https://www.biorxiv.org/content/10.1101/2025.08.12.669910v1
Reposted by Nicholas Southern
natmethods.nature.com
PANCS-Binders (phage-assisted noncontinuous selection of protein binders) screens multiple high-diversity protein libraries against a panel of dozens of targets for high-throughput binder discovery. @chembiobryan.bsky.social @mstyles-chembiol.bsky.social

www.nature.com/articles/s41...
Reposted by Nicholas Southern
natmethods.nature.com
natmethods.nature.com
ProDomino is a machine learning-based method that predicts domain insertion sites and helps guide the engineering of functional multi-domain proteins.

www.nature.com/articles/s41...
Reposted by Nicholas Southern
daylab.bsky.social
Pretty sure my grandfather, who was a NASA engineer that worked on Saturn and Apollo missions in Alabama in the 1960s and 1970s, would be alarmed to see what’s happening now. This is faded but here is a technical drawing he produced for fiber optic viewing of the liquid oxygen supply for Saturn V.
Reposted by Nicholas Southern
martinpacesa.bsky.social
I am super excited to announce that I will be starting my lab at the Department of Pharmacology of the University of Zurich in Switzerland next year!
Reposted by Nicholas Southern
biorxiv-bioeng.bsky.social
Engineering site-specific nucleic acid-protein conjugates by utilizing a natural RNAylation reaction https://www.biorxiv.org/content/10.1101/2025.07.11.664405v1
Reposted by Nicholas Southern
hannahledvina.bsky.social
Words cannot describe how excited I am to share the findings from the second half of my postdoc in @aaronwhiteley.bsky.social's lab where we discover that bacteria use functional amyloids to defend themselves from predatory bacteria. rdcu.be/euu5Y. See thread for details on this epic adventure 1/.
Functional amyloid proteins confer defence against predatory bacteria
Nature - Escherichia coli uses curli fibres, oligomers of the functional amyloid CsgA, as a barrier to protect against the predatory bacteria Bdellovibrio bacteriovorus and Myxococcus xanthus in a...
rdcu.be
Reposted by Nicholas Southern
martinpacesa.bsky.social
We have written up a tutorial on how to run BindCraft, how to prepare your input PDB, how to select hotspots, and various other tips and tricks to get the most out of binder design!

github.com/martinpacesa...