John Ngo

Today I'd like to honor the memory of my mentor and friend, Roger Tsien, born 1952 February 1. Today would have been Roger's 74th birthday.

Most know Roger for his 2008 Chemistry Nobel Prize with Shimomura and Chalfie. Roger made GFP into the versatile imaging method it is now.

Careers - Calico

I'm excited to be hiring an intern to develop new fluorescence-based assays for alpha synuclein aggregation at Calico during summer 2026 😃 🔬

If you're a current PhD student who loves microscopy, unnatural amino acids, and/or synuclein biophysics, please apply!

www.calicolabs.com/careers/?gh_...

Ah yes... "Non-Canonical Amino Acids"... the "accents" of life's alphabet... So hot right now! 🧑‍🔬

Computrs usd a rstrictd alphabt to dsign protins that fold & “mak sns.”

@natbiomedeng.nature.com had a 🔥🔥 week this week! Why don't we have any followers on this site 😆😭

Such a talent! And clearly, one is expressing GFP...

“Force”-ing this back into your feeds since I forgot to add the ReadCube link! rdcu.be/eKLv5

Synthetic mechanotransduction Nature Reviews Bioengineering - Cells convert mechanical forces into biochemical signals through mechanotransduction, a process which can now be synthetically engineered. In this Review, we examine...

Glad you commented! Here’s the ReadCube link! rdcu.be/eKLv5

Synthetic mechanotransduction - Nature Reviews Bioengineering Cells convert mechanical forces into biochemical signals through mechanotransduction, a process which can now be synthetically engineered. In this Review, we examine engineered artificial mechanotrans...

Pleased to share our review on “Synthetic Mechanotransduction” — now live at Nature Reviews Bioengineering.

May the force be with you!

www.nature.com/articles/s44...

Synthetic mechanotransduction Nature Reviews Bioengineering, Published online: 13 October 2025; doi:10.1038/s44222-025-00366-7Cells convert mechanical forces into biochemical signals through mechanotransduction, a process which can now be synthetically engineered. In this Review, we examine engineered artificial mechanotransduction mechanisms, from gene circuits responsive to mechanical cues to synthetic force-generating systems that reshape tissue behaviour and cellular function.

Synthetic mechanotransduction

A Bacteroides fragilis protease activates host PAR2 to induce intestinal pain and inflammation Lakemeyer and colleagues analyze the secretome of gut bacteria to identify factors that target host PAR2. They find that the Bacteroides fragilis protease Bfp1 cleaves and activates PAR2, disrupting i...

After a long journey and much hard work from many talented scientists, our paper is finally out. Take a look if you are interested in proteases and host microbe interactions in the gut. www.cell.com/cell-host-mi...

Engineering synthetic agonists for targeted activation of Notch signaling - Nature Chemical Biology The development of soluble Notch agonists is a challenge because of the mechanical forces needed to activate Notch receptors. Here, bispecific Notch agonist proteins were designed that ‘pull’ on and activate Notch receptors in the presence of desired biomarkers.

Engineered bispecific Notch agonists “pull” on and mechanically activate Notch receptors in the presence of desired biomarkers

www.nature.com/articles/s41...

Leaflet-specific phospholipid imaging using genetically encoded proximity sensors - Nature Chemical Biology An approach combining bioorthogonal chemistry with genetically encoded fluorogen-activating proteins enables subcellular imaging of phospholipids and glycans, as well as the visualization of lipid tra...

Very excited to share new work out today in @natchembio.nature.com on a new approach - FACES - for selectively imaging of phospholipids and other biomolecules at spatial resolutions down to individual membrane leaflets (1/n) www.nature.com/articles/s41...

Wow—thank you so much Evelina! We have long been inspired by your work! Please let us know what you see (and let us know if we can help!). 😎

Many thanks, Gal!!! We’re excited to see the paper live online! =)

Thanks Brian! it was a a fun project led by two super talented students. Glad you like the movies! 😎

Thanks Dan! We hope so. Plasmids are on AddGene… let us know what you see!

4️⃣ Plasmids are on #AddGene!
www.addgene.org/browse/artic...

3️⃣ Future synthetic biology utilities:

Right now, we are fusing these proteins to #synbio effectors and adaptors to:
• control RNA fate,
• boost CRISPR/dCas9 RNA scaffolds,
• reduce off-target labeling
enabling next-gen RNA–protein circuits for synthetic regulation and control.

2️⃣ Advantages in Imaging & Controlling Single mRNAs:

• Single-mRNA sensitivity using 1×mNeonGreen fusions in live #imaging

• Track the localization & translation #mRNAs encoding cytoplasmic, nuclear, mitochondrial & secreted proteins

• Direct #mRNA localization by fusing dMCP to targeting signals

1️⃣ Mechanism & protein engineering:

Through circular permutation + degron masking, we designd dMCP & dPCP to be rapidly degraded unless bound to their cognate #RNA hairpins (MS2 & PP7). Hairpin binding switches them from unstable to bright, RNA-bound reporters via a #degron masking mechanism.

🚀 Our new paper is out @natmethods.nature.com!

Kuffer & Marzilli engineered conditionally stable MS2 & PP7 coat proteins (dMCP & dPCP) that degrade unless bound to RNA, enabling ultra–low-background, single-mRNA imaging in live cells.

🔗 www.nature.com/articles/s41...
🧬 www.addgene.org/John_Ngo/

Do what you love and love what you do, and if you can, leave the world a better, more open, and more understanding place.

My lab at BU is looking to hire a post-doc with experience in biophysics, protein engineering, and chemical (or synthetic) biology. The anticipated start date is Jan 2026. Please send a resume, cover letter, and names/emails for 3 references. We are looking to interview people during Sept/Oct 2025.

Please RT 🙏 If you’re an early career researcher working in the fields of structural or synthetic biology wishing to start your lab then come join us at Imperial. We’re looking to support outstanding individuals for external Career Development Awards/Fellowships.

www.imperial.ac.uk/media/imperi...

Congratulations, Rita!! And thank you for all the awesome work you do. Nature Biomedical Engineering is lucky to have you at the helm!

A world without science is one without hope and progress!

For those who can, and while you are in it, give science, knowledge, possibility, and hope your full effort. We’re counting on you. It’ll be worth it… trust me.

For those who can, and while you are in it, give science, knowledge, possibility, and hope your full effort. We’re counting on you. It’ll be worth it… trust me.

Everybody be you and keep going. Do your best. We are so proud of you!