Gene circuit-driven amplified selection enables evolution of fast-growing Escherichia coli https://www.biorxiv.org/content/10.64898/2026.08.05.743033v1
Nicholas Southern
@neuroscinikolai.bsky.social
PhD Student @ https://niopeklab.de/ Engineering switchable proteins💡 Views and opinions are my own 🇺🇸 in 🇩🇪
Nice method analogous to our RAMPhaGE system but applied to conjugation instead of phages for gene evolution
bioRxiv Synthetic Biology@biorxiv-synthbio.bsky.social · 4w agoContinuous site-directed mutagenesis and selection in Escherichia coli https://www.biorxiv.org/content/10.64898/2026.07.18.739322v1
Can we program a kinase like a switch? Inspired by natural autoinhibitory complexes, we designed miniproteins against active- and inactive-like conformations of Focal Adhesion Kinase. Depending on the targeted state, the resulting binders either activated or inhibited the kinase.
Protein Surface Site Determines the Evolutionary Accessibility of Allosteric Regulation https://www.biorxiv.org/content/10.64898/2026.07.02.735819v1
New preprint! We used protein domain insertion to tighten the editing window of the TadA8e adenine base editor. Bulky domain insertions concentrated editing around position A5, maintained robust on-target activity, and reduced Cas-independent off-target editing. 🧬 doi.org/10.64898/202...
Domain Insertion Improves the Precision of a CRISPR Adenine Base Editor
Adenine base editors (ABEs) enable efficient A:T to G:C conversion, but their broad activity windows frequently cause unintended bystander edits. We hypothesized that insertion of a bulky, inert prote...
biorxiv.org
If you missed the preprint, now is a good time to read the journal version of @grocklin.bsky.social et al’s fantastic paper on multiplexed HDX measurements Large-scale discovery, analysis and design of protein energy landscapes doi.org/10.1038/s415...
bioRxiv Biophysics@biorxiv-biophys.bsky.social · last yr.Large-scale discovery, analysis, and design of protein energy landscapes https://www.biorxiv.org/content/10.1101/2025.03.20.644235v1
Bridge recombinase enables versatile rewriting of bacterial genomes https://www.biorxiv.org/content/10.64898/2026.04.29.721476v1
Excited to share that our AzoTag paper is now out in @natchem.nature.com! 🥳 We demonstrate de novo chemo-optogenetics through the rational design of photoresponsive small molecules and selection of their artificial protein binding pairs. www.nature.com/articles/s41...
De novo chemo-optogenetics through the rational design of photoresponsive molecules and selection of their artificial protein binding pairs - Nature Chemistry
Optical manipulation of proteins is central to modulating and characterizing biomolecular functions in cell biology, but tools based on natural proteins are difficult to reconfigure for desired photoc...
nature.com
Out now in Nature Biotechnology! Alejandro González-Delgado and a fantastic team of collaborators worked across nine labs to get retron recombineering up-and-running in fifteen bacterial species. Molecular parts on addgene: www.addgene.org/browse/artic... Happy editing!
Nature Biotechnology@natbiotech.nature.com · 4mo agoGenome editing of phylogenetically distinct bacteria using cross-species retron-mediated recombineering - @seth-shipman.bsky.social @gladstoneinst.bsky.social go.nature.com/4tZluOU
Don't be shy to take on a little two-week side project. These five months will be the most precious three years of your academic journey.
GROQ-seq Datasets Across Transcription Factors (LacI, RamR, VanR), T7 RNA Polymerase and TEV Protease https://www.biorxiv.org/content/10.64898/2026.04.15.718744v1
I am so excited to share our new findings with you! We provide the structural evidence for a direct protein-to-DNA information pathway, showing how a bacterial enzyme 'reads' its own structure to 'write' DNA. www.science.org/doi/10.1126/...
🔈Paper out! We turned the most fascinating phage host-switch mechanism, diversity-generating retroelements, into a programmable mutagenesis tool, DGRec. You can perform targeted hypermutation of any 50-200bp sequence directly in vivo in E. coli www.nature.com/articles/s41...
Diversity-generating retroelements for programmable targeted hypermutagenesis - Nature Biotechnology
Diversity-generating retroelements are engineered for directed evolution in E.coli.
nature.com
New paper from the lab on phage-assisted evolution of allosteric light-switches now out in Nature Comms. Congratulations to Nick and all co-authors! www.nature.com/articles/s41...
Phage-assisted evolution of allosteric protein switches - Nature Communications
Allostery enables proteins to respond to signals but remains difficult to engineer. Here, Southern et al. developed a phage-assisted evolution framework for allosteric protein switches yielding high-p...
nature.com
Nicholas Southern@neuroscinikolai.bsky.social · 4mo ago1/28 How do you optimize a dynamic protein property that emerges from multiple states? Our finally published paper in @NatureComms takes on one of the hardest problems in protein engineering with phage assisted evolution: evolving allosteric switches🧵
1/28 How do you optimize a dynamic protein property that emerges from multiple states? Our finally published paper in @NatureComms takes on one of the hardest problems in protein engineering with phage assisted evolution: evolving allosteric switches🧵
Check out this incredible new method for the directed evolution of protein ON/OFF switches!!! www.cell.com/cell/fulltex...
Light-directed evolution of dynamic, multi-state, and computational protein functionalities
Optovolution leverages optogenetics and the yeast cell cycle to impose rapid, tunable selection, enabling the continuous evolution of light-responsive regulators, logic gates, and other complex protei...
cell.com
Vorholt Lab re-created endosymbiosis in the lab: injected bacteria into a fungus and evolved a heritable partnership. Evolution, fast-forwarded. doi.org/10.1038/s415...
Inducing novel endosymbioses by implanting bacteria in fungi - Nature
A study presents an approach to establish and track a new endosymbiotic partnership by implanting bacteria in a non-host fungus and shows that stable inheritance of the implanted bacteria is possible ...
doi.org
🎉🎉 Our paper on temperature-dependent protein control using AsLOV2 variants is now published at @natchembio.nature.com: www.nature.com/articles/s41... including some new insights from extend variant characterizations.
Modular engineering of thermoresponsive allosteric proteins - Nature Chemical Biology
Thermogenetics enables spatiotemporal control of protein activity using temperature. Now, engineering of a compact, insertable thermoresponsive protein module diversifies the classes of proteins amena...
nature.com
Jan Mathony@jmathony.bsky.social · last yr.New paper alert! We introduce the modular allosteric thermo-control of protein activity. Employing the AsLOV2 domain and mutants thereof as thermoreceptors, we engineered diverse hybrid proteins, whose activity can be controlled by small temperature changes (37-40/41 °C). doi.org/10.1101/2025...
Our research on magneto-sensitive fluorescent proteins and some of their applications has now been published! Huge thank you to the many many people involved in making this happen. 🧪 www.nature.com/articles/s41...
Quantum spin resonance in engineered proteins for multimodal sensing - Nature
A recently developed class of magneto-sensitive fluorescent proteins are engineered to alter the properties of their response to magnetic fields and radio frequencies, enabling multimodal sensing of b...
nature.com
Nature has a trick to evolve multimeric proteins via gene duplication. 🧬One copy compensates, the other explores.🧬 Although this has only been a theory so far. Until now: Directed evolution of multimeric proteins by dual-compensatory gene duplication. www.biorxiv.org/content/10.6...
With the state of biomedical science in the U.S. becoming increasingly uncertain, definitely consider these options if you’re a student. I’ve had a great experience doing my PhD in Germany—strong research, supportive environment, and a reasonable cost of living. Happy to share advice if interested!
Harmit Singh Malik@harmitmalik.bsky.social · last yr.Many US students don’t know how to seek opportunities outside the US. With some help from our colleagues in EU and Canada, we could put together a consolidated website of PhD opportunities and scholarships outside the US, organized by field. There might still be time for this year in some places.
Join us for a 📢 #CIBSS / SFB 1381 Joint Seminar 🗓 13 Jan 2026 | 12:00–13:00 👉 @jmathony.bsky.social (#uniheidelberg) 🎙 Engineering stimulus-controlled proteins through modular domain recombination 📍 Lecture Hall, Institute of Biology I, Hauptstr. 1 🔗 kurzlinks.de/4mlv #SynBio #ProteinEngineering
1/ Check out our newest paper where we ask: How fast can we experimentally discover binders from scratch? And we mean scratch: a blinded study. TLDR: 26 days. And the binders work…and led to new cancer biology. We’re coming for you AI…. chemrxiv.org/engage/chemr...
Bacterial genomes encode a rich repertoire of antiphage systems, but we still know surprisingly little about when these systems are actually expressed. In this preprint, Lucas Paoli et al, ask what shapes antiphage systems expression in native contexts. www.biorxiv.org/content/10.6...
Environment and physiology shape antiphage system expression
Bacteria and archaea encode on average ten antiphage systems. Quorum sensing, cellular, or transcription factors can regulate specific systems (CRISPR-Cas, CBASS). Yet, a systematic assessment of anti...
biorxiv.org
We are hiring a lab manager, for our research group, the Synthetic Neurobiology group (aka Boyden Lab) at MIT/HHMI (on the MIT campus, Cambridge, MA)! Please apply if you're qualified and interested, and spread the word! hhmi.wd1.myworkdayjobs.com/External/job...
Laboratory Manager II - Boyden Lab
Primary Work Address: 77 Massachusetts Avenue, Cambridge, MA, 02139 Current HHMI Employees, click here to apply via your Workday account. The Synthetic Neurobiology Group (Boyden Lab) at the MIT McGov...
hhmi.wd1.myworkdayjobs.com
Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells https://www.biorxiv.org/content/10.64898/2025.12.11.693673v1
An ultra-low background far-red light-responsive optogenetic tool based on an engineered biliverdin-binding domain https://www.biorxiv.org/content/10.1101/2025.11.29.691301v1
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.
Nicholas Southern@neuroscinikolai.bsky.social · last yr.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.