Nicholas Southern
@neuroscinikolai.bsky.social
PhD Student @ https://niopeklab.de/
Engineering switchable proteins💡
Views and opinions are my own
🇺🇸 in 🇩🇪
Engineering switchable proteins💡
Views and opinions are my own
🇺🇸 in 🇩🇪
Pinned
Phage-Assisted Evolution of Allosteric Protein Switches https://www.biorxiv.org/content/10.1101/2025.06.12.659331v1
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 🌚🌞
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 🌚🌞
Especially today, as the administration sidelines evidence-based policy decisions and pressures scientific institutions, this bears repeating:
A strong, well-funded, and politically independent scientific ecosystem is vital to innovation, national security, and public health. The stakes are clear.
A strong, well-funded, and politically independent scientific ecosystem is vital to innovation, national security, and public health. The stakes are clear.
I left the US in 2022 to pursue a PhD abroad, partly out of concern for the sustainability of our politics.
I’m grateful to live where people reckon with the dangers of unchecked power, and I stand—both as an American and a scientist—with those who defend truth, integrity, and limits on authority.
I’m grateful to live where people reckon with the dangers of unchecked power, and I stand—both as an American and a scientist—with those who defend truth, integrity, and limits on authority.
October 18, 2025 at 12:48 PM
Especially today, as the administration sidelines evidence-based policy decisions and pressures scientific institutions, this bears repeating:
A strong, well-funded, and politically independent scientific ecosystem is vital to innovation, national security, and public health. The stakes are clear.
A strong, well-funded, and politically independent scientific ecosystem is vital to innovation, national security, and public health. The stakes are clear.
Reposted by Nicholas Southern
Great to see our MOSAIC story about an easy, cloning-free efficient protocol for mutating plasmids using recombineering is out now officially and the cover story of ASC Synthetic Biology pubs.acs.org/toc/asbcd6/1... ! Great shoutout to Marijn van den Brink, Tim Althuis and Christophe Danelon!
ACS Synthetic Biology
We introduce MOSAIC, a highly efficient protocol for the editing of plasmids and generation of combinatorial plasmid libraries. This quick protocol employs the single-stranded DNA annealing protein Cs...
pubs.acs.org
October 17, 2025 at 8:39 AM
Great to see our MOSAIC story about an easy, cloning-free efficient protocol for mutating plasmids using recombineering is out now officially and the cover story of ASC Synthetic Biology pubs.acs.org/toc/asbcd6/1... ! Great shoutout to Marijn van den Brink, Tim Althuis and Christophe Danelon!
Reposted by Nicholas Southern
1/10 Genome maintenance by telomerase is a fundamental process in nearly all eukaryotes. But where does it come from?
Today, we report the discovery of telomerase homologs in a family of antiviral RTs, revealing an unexpected evolutionary origin in bacteria.
www.biorxiv.org/content/10.1...
Today, we report the discovery of telomerase homologs in a family of antiviral RTs, revealing an unexpected evolutionary origin in bacteria.
www.biorxiv.org/content/10.1...
Antiviral reverse transcriptases reveal the evolutionary origin of telomerase
Defense-associated reverse transcriptases (DRTs) employ diverse and distinctive mechanisms of cDNA synthesis to protect bacteria against viral infection. However, much of DRT family diversity remains ...
www.biorxiv.org
October 17, 2025 at 5:22 PM
1/10 Genome maintenance by telomerase is a fundamental process in nearly all eukaryotes. But where does it come from?
Today, we report the discovery of telomerase homologs in a family of antiviral RTs, revealing an unexpected evolutionary origin in bacteria.
www.biorxiv.org/content/10.1...
Today, we report the discovery of telomerase homologs in a family of antiviral RTs, revealing an unexpected evolutionary origin in bacteria.
www.biorxiv.org/content/10.1...
Reposted by Nicholas Southern
Mapping the diverse topologies of protein-protein interaction fitness landscapes https://www.biorxiv.org/content/10.1101/2025.10.14.682342v1
October 15, 2025 at 3:03 AM
Mapping the diverse topologies of protein-protein interaction fitness landscapes https://www.biorxiv.org/content/10.1101/2025.10.14.682342v1
Reposted by Nicholas Southern
New Hot Topics piece from @rphillips3.bsky.social and Stephanie Page in @npp-journal.bsky.social describing emerging insights on roles of molecularly-defined cell types in the lateral septum, which serves as a hub for coordinating diverse social behaviors.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Role of molecularly defined lateral septum cell types and circuits in social behaviors - Neuropsychopharmacology
Neuropsychopharmacology - Role of molecularly defined lateral septum cell types and circuits in social behaviors
www.nature.com
September 30, 2025 at 9:30 PM
New Hot Topics piece from @rphillips3.bsky.social and Stephanie Page in @npp-journal.bsky.social describing emerging insights on roles of molecularly-defined cell types in the lateral septum, which serves as a hub for coordinating diverse social behaviors.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Reposted by Nicholas Southern
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...
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
September 24, 2025 at 12:41 PM
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...
www.bbc.com/news/article...
www.bbc.com/news/article...
Reposted by Nicholas Southern
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…
September 10, 2025 at 3:40 PM
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…
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 😄
September 8, 2025 at 7:55 AM
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 😄
Reposted by Nicholas Southern
🚀 New publication alert! 🚀
We just published in @natbiotech.nature.com:
👉 Targeted DNA ADP-ribosylation triggers templated repair in bacteria and base mutagenesis in eukaryotes
doi.org/10.1038/s415...
We just published in @natbiotech.nature.com:
👉 Targeted DNA ADP-ribosylation triggers templated repair in bacteria and base mutagenesis in eukaryotes
doi.org/10.1038/s415...
Targeted DNA ADP-ribosylation triggers templated repair in bacteria and base mutagenesis in eukaryotes - Nature Biotechnology
Append editing of ADP-ribosyl to thymine is used for precise modifications in bacteria and eukaryotes.
doi.org
September 4, 2025 at 6:51 PM
🚀 New publication alert! 🚀
We just published in @natbiotech.nature.com:
👉 Targeted DNA ADP-ribosylation triggers templated repair in bacteria and base mutagenesis in eukaryotes
doi.org/10.1038/s415...
We just published in @natbiotech.nature.com:
👉 Targeted DNA ADP-ribosylation triggers templated repair in bacteria and base mutagenesis in eukaryotes
doi.org/10.1038/s415...
Reposted by Nicholas Southern
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
🧵
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
September 2, 2025 at 10:48 AM
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
🧵
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
🧵
Reposted by Nicholas Southern
Growth, dissolution and segregation of genetically encoded RNA droplets by ribozyme catalysis https://www.biorxiv.org/content/10.1101/2025.08.29.673008v1
August 30, 2025 at 4:14 AM
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
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...
www.nature.com/articles/s41...
August 27, 2025 at 4:14 PM
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...
www.nature.com/articles/s41...
Reposted by Nicholas Southern
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.
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.
August 17, 2025 at 1:35 AM
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.
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
De novo design of light-regulated dynamic proteins using deep learning https://www.biorxiv.org/content/10.1101/2025.08.12.669910v1
August 13, 2025 at 2:50 PM
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
Reposted by Nicholas Southern
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...
www.nature.com/articles/s41...
August 6, 2025 at 7:49 PM
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...
www.nature.com/articles/s41...
Reposted by Nicholas Southern
Work by @bene837.bsky.social @jmathony.bsky.social @dominikniopek.bsky.social @uniheidelberg.bsky.social
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...
www.nature.com/articles/s41...
August 4, 2025 at 3:26 PM
Reposted by Nicholas Southern
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.
July 29, 2025 at 12:08 AM
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
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!
July 25, 2025 at 7:48 AM
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
Engineering site-specific nucleic acid-protein conjugates by utilizing a natural RNAylation reaction https://www.biorxiv.org/content/10.1101/2025.07.11.664405v1
July 17, 2025 at 3:46 AM
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
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
July 2, 2025 at 8:10 PM
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/.
Reposted by Nicholas Southern
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...
github.com/martinpacesa...
June 30, 2025 at 7:45 PM
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...
github.com/martinpacesa...
Reposted by Nicholas Southern
Let’s we flip this script.
“Is academia producing too few jobs?”
“Is academia producing too few jobs?”
June 30, 2025 at 12:53 PM
Let’s we flip this script.
“Is academia producing too few jobs?”
“Is academia producing too few jobs?”
Reposted by Nicholas Southern
We have developed an entirely new mechanism of action for gene knockdown -> trafficking of targeted mRNAs to the lysosomal, using lysosomal trafficking oligonucleotides (LyTONs)!
Published in @chemicalscience.rsc.org
Led by Disha Kashyap
#chemsky 🧪
pubs.rsc.org/en/content/a...
Published in @chemicalscience.rsc.org
Led by Disha Kashyap
#chemsky 🧪
pubs.rsc.org/en/content/a...
Engineering antisense oligonucleotides for targeted mRNA degradation through lysosomal trafficking
Antisense oligonucleotides (ASOs) can modulate gene expression at the mRNA level, providing the ability to tackle conventionally undruggable targets and usher in an era of personalized medicine. A key...
pubs.rsc.org
June 23, 2025 at 8:01 AM
We have developed an entirely new mechanism of action for gene knockdown -> trafficking of targeted mRNAs to the lysosomal, using lysosomal trafficking oligonucleotides (LyTONs)!
Published in @chemicalscience.rsc.org
Led by Disha Kashyap
#chemsky 🧪
pubs.rsc.org/en/content/a...
Published in @chemicalscience.rsc.org
Led by Disha Kashyap
#chemsky 🧪
pubs.rsc.org/en/content/a...
Reposted by Nicholas Southern
Happy to announce the first paper from my PhD at Korbel group at @embl.org has finally been published:
embopress.org/doi/full/10.1038…
Collaborating with @typaslab.bsky.social, @hennig-lab.bsky.social and the EMBL PEPCF, we designed de novo inhibitors to a bacterial phage defense system 1/🧵
embopress.org/doi/full/10.1038…
Collaborating with @typaslab.bsky.social, @hennig-lab.bsky.social and the EMBL PEPCF, we designed de novo inhibitors to a bacterial phage defense system 1/🧵
June 19, 2025 at 8:10 AM
Happy to announce the first paper from my PhD at Korbel group at @embl.org has finally been published:
embopress.org/doi/full/10.1038…
Collaborating with @typaslab.bsky.social, @hennig-lab.bsky.social and the EMBL PEPCF, we designed de novo inhibitors to a bacterial phage defense system 1/🧵
embopress.org/doi/full/10.1038…
Collaborating with @typaslab.bsky.social, @hennig-lab.bsky.social and the EMBL PEPCF, we designed de novo inhibitors to a bacterial phage defense system 1/🧵