William J Nicolas
@wjnicol.bsky.social
Senior scientist @ Exelixis | Cryo-EM facility lead
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PhD @ CNRS | LBM-Bayer lab
Postdoc @ Jensen/Meyerowitz lab Caltech
Cryo-EM facility manager @ Gonen lab HHMI
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Website: www.wjnicolas.com
Twitter handle: @WiwiSFC
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PhD @ CNRS | LBM-Bayer lab
Postdoc @ Jensen/Meyerowitz lab Caltech
Cryo-EM facility manager @ Gonen lab HHMI
--
Website: www.wjnicolas.com
Twitter handle: @WiwiSFC
Pinned
William J Nicolas
@wjnicol.bsky.social
· Mar 27
Structure of the lens MP20 mediated adhesive junction - Nature Communications
Human lens clarity and function depends on well-organized cell junctions. Here, the authors used MicroED to reveal the 3.5 Å structure of MP20, showing that MP20 tetramers form adhesive junctions esse...
www.nature.com
Happy to share the latest work from the Gonen lab! A collective effort to solve the structure of the lens membrane protein central to keeping our lenses transparent!
Fluorescent targeted FIB milling, LCP and microED made this possible!
www.nature.com/articles/s41...
Fluorescent targeted FIB milling, LCP and microED made this possible!
www.nature.com/articles/s41...
Reposted by William J Nicolas
Initial attempt at replicating in relion (parameters in next post). This is for Aca2-RNA, using a 100k subset of the 2D-classified particles (no prior 3D cleanup).
A 1-class ab initio in relion, then local refinement in relion (1.8deg searches+blush) gives a nominally 3.3Å map; 3.5 Å w/out blush.
A 1-class ab initio in relion, then local refinement in relion (1.8deg searches+blush) gives a nominally 3.3Å map; 3.5 Å w/out blush.
September 26, 2025 at 2:28 AM
Initial attempt at replicating in relion (parameters in next post). This is for Aca2-RNA, using a 100k subset of the 2D-classified particles (no prior 3D cleanup).
A 1-class ab initio in relion, then local refinement in relion (1.8deg searches+blush) gives a nominally 3.3Å map; 3.5 Å w/out blush.
A 1-class ab initio in relion, then local refinement in relion (1.8deg searches+blush) gives a nominally 3.3Å map; 3.5 Å w/out blush.
Reposted by William J Nicolas
A molecular-resolution look into the near-native architecture of the spinach chloroplast🌱. This one was a long time in the oven, but we're happy to finally share our "version of record". What long-standing debates did we settle? Check back for a short thread🧵 on Monday. #TeamTomo #PlantScience 🧪🧶🧬🔬🌾
🌱 Using ‘compelling’ methods, including #CryoET, researchers mapped spinach thylakoid membranes at single-molecule precision, revealing how photosynthetic complexes are organised and settling long-standing debates on chloroplast architecture.
buff.ly/j3TSIkn
buff.ly/j3TSIkn
September 20, 2025 at 7:24 PM
A molecular-resolution look into the near-native architecture of the spinach chloroplast🌱. This one was a long time in the oven, but we're happy to finally share our "version of record". What long-standing debates did we settle? Check back for a short thread🧵 on Monday. #TeamTomo #PlantScience 🧪🧶🧬🔬🌾
Absolutely!
PSA: 9 billion USD in research funds stolen by publishers over a 5 year period for open access fees - this takes away from your ability to pay your people what they are worth. Preprints forever.
September 21, 2025 at 10:12 PM
Absolutely!
Reposted by William J Nicolas
If you are thinking about the future of structural biology, we are too! Our two cents (Jürgen Plitzko and I) just got published online here: authors.elsevier.com/sd/article/S...
August 23, 2025 at 11:21 PM
If you are thinking about the future of structural biology, we are too! Our two cents (Jürgen Plitzko and I) just got published online here: authors.elsevier.com/sd/article/S...
Reposted by William J Nicolas
New Title Alert: AITom- an open-source platform for AI driven cellular electron cryo-tomography analysis.
Learn more here: buff.ly/LLGhjvY
#SBGrid #SBGridSoftware #StructuralBiology
Learn more here: buff.ly/LLGhjvY
#SBGrid #SBGridSoftware #StructuralBiology
Research
Xu Lab of Computational Biology
buff.ly
August 12, 2025 at 4:03 PM
New Title Alert: AITom- an open-source platform for AI driven cellular electron cryo-tomography analysis.
Learn more here: buff.ly/LLGhjvY
#SBGrid #SBGridSoftware #StructuralBiology
Learn more here: buff.ly/LLGhjvY
#SBGrid #SBGridSoftware #StructuralBiology
Reposted by William J Nicolas
New preprint: In situ Architecture of #Plasmodesmata.
Using #cryoET, #AlphaFold & proteomics, we uncover the native organization of plant intercellular nanopores.
🔗 doi.org/10.1101/2025...
🧪🧵1/n
#teamtomo #PlantScience #Physcomitrium #Arabidopsis #cryoEM
Using #cryoET, #AlphaFold & proteomics, we uncover the native organization of plant intercellular nanopores.
🔗 doi.org/10.1101/2025...
🧪🧵1/n
#teamtomo #PlantScience #Physcomitrium #Arabidopsis #cryoEM
July 26, 2025 at 3:38 PM
New preprint: In situ Architecture of #Plasmodesmata.
Using #cryoET, #AlphaFold & proteomics, we uncover the native organization of plant intercellular nanopores.
🔗 doi.org/10.1101/2025...
🧪🧵1/n
#teamtomo #PlantScience #Physcomitrium #Arabidopsis #cryoEM
Using #cryoET, #AlphaFold & proteomics, we uncover the native organization of plant intercellular nanopores.
🔗 doi.org/10.1101/2025...
🧪🧵1/n
#teamtomo #PlantScience #Physcomitrium #Arabidopsis #cryoEM
Reposted by William J Nicolas
Our methods paper made it to bioRxiv:
doi.org/10.1101/2025...
Full #cryoET workflows for #plant tissues. Plus some general tricks and tweaks on serial Lift-Out and cryo-FLM. 🧪🧵1/5
#teamtomo #PlantScience #Physcomitrium #Arabidopsis #cryoEM #CLEM
doi.org/10.1101/2025...
Full #cryoET workflows for #plant tissues. Plus some general tricks and tweaks on serial Lift-Out and cryo-FLM. 🧪🧵1/5
#teamtomo #PlantScience #Physcomitrium #Arabidopsis #cryoEM #CLEM
February 19, 2025 at 6:06 AM
Our methods paper made it to bioRxiv:
doi.org/10.1101/2025...
Full #cryoET workflows for #plant tissues. Plus some general tricks and tweaks on serial Lift-Out and cryo-FLM. 🧪🧵1/5
#teamtomo #PlantScience #Physcomitrium #Arabidopsis #cryoEM #CLEM
doi.org/10.1101/2025...
Full #cryoET workflows for #plant tissues. Plus some general tricks and tweaks on serial Lift-Out and cryo-FLM. 🧪🧵1/5
#teamtomo #PlantScience #Physcomitrium #Arabidopsis #cryoEM #CLEM
'cux good data don't wait!
July 24, 2025 at 4:11 PM
'cux good data don't wait!
Reposted by William J Nicolas
Outstanding work from Christine, Stan and the whole team on this beautiful story. Wow.
Happy to share our latest work on the structure and assembly of holocentric kinetochores! Huge thanks to Ines for a very fruitful collaboration, Claudio for all the support, and congratulations to Christine and all co-authors!
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
July 17, 2025 at 1:44 PM
Outstanding work from Christine, Stan and the whole team on this beautiful story. Wow.
Reposted by William J Nicolas
Neural net picker with a truly general model - no per dataset training required (at least if it works as advertised). Want to try this on some messy/mixed samples where other approaches struggle!
July 9, 2025 at 1:03 PM
Neural net picker with a truly general model - no per dataset training required (at least if it works as advertised). Want to try this on some messy/mixed samples where other approaches struggle!
Reposted by William J Nicolas
Running Phenix and stuck?
Now you can ask the new Phenix chatbot anything from the 600-page tutorial about how to run any program.
Big thanks to Tom Willinger for making this happen!
Try it out: phenix-online.org/version_docs...
Now you can ask the new Phenix chatbot anything from the 600-page tutorial about how to run any program.
Big thanks to Tom Willinger for making this happen!
Try it out: phenix-online.org/version_docs...
June 23, 2025 at 5:15 AM
Running Phenix and stuck?
Now you can ask the new Phenix chatbot anything from the 600-page tutorial about how to run any program.
Big thanks to Tom Willinger for making this happen!
Try it out: phenix-online.org/version_docs...
Now you can ask the new Phenix chatbot anything from the 600-page tutorial about how to run any program.
Big thanks to Tom Willinger for making this happen!
Try it out: phenix-online.org/version_docs...
Frostbyte 🥶 socks provided by @hammerspace.com
June 16, 2025 at 3:48 PM
Frostbyte 🥶 socks provided by @hammerspace.com
Reposted by William J Nicolas
And it’s done! Thanks to everyone who came out for the first edition of FrostByte, our event for the local computational cryo-EMers in the Bay Area ❄️
Special thanks to @joshdcryoem.bsky.social and Ariana Peck for help organizing 🙏
Special thanks to @joshdcryoem.bsky.social and Ariana Peck for help organizing 🙏
June 12, 2025 at 1:45 AM
And it’s done! Thanks to everyone who came out for the first edition of FrostByte, our event for the local computational cryo-EMers in the Bay Area ❄️
Special thanks to @joshdcryoem.bsky.social and Ariana Peck for help organizing 🙏
Special thanks to @joshdcryoem.bsky.social and Ariana Peck for help organizing 🙏
Reposted by William J Nicolas
This paper combines two sort-of-crazy (in the best sense) approaches in cryoEM sample preparation:
(1) Native, soft-landing electrospray ion beam deposition, followed by (2) deposition of amorphous ice, and reheating and freezing by laser flash melting. Has potential for time-resolved studies.
(1) Native, soft-landing electrospray ion beam deposition, followed by (2) deposition of amorphous ice, and reheating and freezing by laser flash melting. Has potential for time-resolved studies.
June 9, 2025 at 6:43 AM
This paper combines two sort-of-crazy (in the best sense) approaches in cryoEM sample preparation:
(1) Native, soft-landing electrospray ion beam deposition, followed by (2) deposition of amorphous ice, and reheating and freezing by laser flash melting. Has potential for time-resolved studies.
(1) Native, soft-landing electrospray ion beam deposition, followed by (2) deposition of amorphous ice, and reheating and freezing by laser flash melting. Has potential for time-resolved studies.
Reposted by William J Nicolas
Reposted by William J Nicolas
Reposted by William J Nicolas
This is a view from the surface of Comet 67P.
The busy particles in the foreground are cosmic rays or bits of dust and ice.
The dots moving in the background are stars.
The busy particles in the foreground are cosmic rays or bits of dust and ice.
The dots moving in the background are stars.
May 23, 2025 at 5:27 PM
This is a view from the surface of Comet 67P.
The busy particles in the foreground are cosmic rays or bits of dust and ice.
The dots moving in the background are stars.
The busy particles in the foreground are cosmic rays or bits of dust and ice.
The dots moving in the background are stars.
Reposted by William J Nicolas
Excited to share our new @science.org paper! Led by postdocs Ruchao Peng and Xin Xu, we used cryo-EM/ET to reveal the influenza ribonucleoprotein complex structure and its strand-sliding mechanism for RNA synthesis, paving the way for new antivirals.
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Molecular basis of influenza ribonucleoprotein complex assembly and processive RNA synthesis
Influenza viruses replicate and transcribe their genome in the context of a conserved ribonucleoprotein (RNP) complex. By integrating cryo–electron microscopy single-particle analysis and cryo–electro...
www.science.org
May 15, 2025 at 7:51 PM
Excited to share our new @science.org paper! Led by postdocs Ruchao Peng and Xin Xu, we used cryo-EM/ET to reveal the influenza ribonucleoprotein complex structure and its strand-sliding mechanism for RNA synthesis, paving the way for new antivirals.
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Reposted by William J Nicolas
Mass Spec + lasers + cryoEM = COOL SCIENCE!
New research from @coonlab.bsky.social and the Grant Lab combines mass spec to land proteins on TEM grids, a laser to restore protein structure, and cryoEM imaging and analysis to produce 3D reconstructions.
www.mcponline.org/article/S153...
New research from @coonlab.bsky.social and the Grant Lab combines mass spec to land proteins on TEM grids, a laser to restore protein structure, and cryoEM imaging and analysis to produce 3D reconstructions.
www.mcponline.org/article/S153...
Laser-Induced Rehydration of Cryo-Landed Proteins Restores Native Structure
The use of native mass spectrometry (MS) to land biological molecules for subsequent
cryogenic electron microscopy (cryoEM) imaging and three-dimensional reconstruction
has gained momentum in recent y...
www.mcponline.org
May 14, 2025 at 3:12 PM
Mass Spec + lasers + cryoEM = COOL SCIENCE!
New research from @coonlab.bsky.social and the Grant Lab combines mass spec to land proteins on TEM grids, a laser to restore protein structure, and cryoEM imaging and analysis to produce 3D reconstructions.
www.mcponline.org/article/S153...
New research from @coonlab.bsky.social and the Grant Lab combines mass spec to land proteins on TEM grids, a laser to restore protein structure, and cryoEM imaging and analysis to produce 3D reconstructions.
www.mcponline.org/article/S153...
Reposted by William J Nicolas
In the Bay Area? Love computational cryo-EM/ET?
Come join us for the first edition of FrostByte - a meeting for the local computational cryo-EM methods community!
Details and registration at frostbyte-cryoem.github.io
Thanks to @joshdcryoem.bsky.social and Ariana Peck for help organizing!
Come join us for the first edition of FrostByte - a meeting for the local computational cryo-EM methods community!
Details and registration at frostbyte-cryoem.github.io
Thanks to @joshdcryoem.bsky.social and Ariana Peck for help organizing!
May 12, 2025 at 8:01 PM
In the Bay Area? Love computational cryo-EM/ET?
Come join us for the first edition of FrostByte - a meeting for the local computational cryo-EM methods community!
Details and registration at frostbyte-cryoem.github.io
Thanks to @joshdcryoem.bsky.social and Ariana Peck for help organizing!
Come join us for the first edition of FrostByte - a meeting for the local computational cryo-EM methods community!
Details and registration at frostbyte-cryoem.github.io
Thanks to @joshdcryoem.bsky.social and Ariana Peck for help organizing!
Reposted by William J Nicolas
Hey #TeamTomo,
Ever been in need of a tutorial about the fundamentals of cryo-electron tomography? From preprocessing raw frames to high-res subtomogram averaging?
That's why @florentwaltz.bsky.social and I made this website!
tomoguide.github.io
Follow the thread 1 /🧵
#CryoET #CryoEM 🔬🧪
Ever been in need of a tutorial about the fundamentals of cryo-electron tomography? From preprocessing raw frames to high-res subtomogram averaging?
That's why @florentwaltz.bsky.social and I made this website!
tomoguide.github.io
Follow the thread 1 /🧵
#CryoET #CryoEM 🔬🧪
Welcome to TomoGuide
A step-by-step Cryo-ET guide
tomoguide.github.io
May 6, 2025 at 4:27 PM
Hey #TeamTomo,
Ever been in need of a tutorial about the fundamentals of cryo-electron tomography? From preprocessing raw frames to high-res subtomogram averaging?
That's why @florentwaltz.bsky.social and I made this website!
tomoguide.github.io
Follow the thread 1 /🧵
#CryoET #CryoEM 🔬🧪
Ever been in need of a tutorial about the fundamentals of cryo-electron tomography? From preprocessing raw frames to high-res subtomogram averaging?
That's why @florentwaltz.bsky.social and I made this website!
tomoguide.github.io
Follow the thread 1 /🧵
#CryoET #CryoEM 🔬🧪
Reposted by William J Nicolas
"Science is an investment.
We will put forward a new 500 million package for 2025-2027 to support the best and the brightest researchers and scientists from Europe and around the world."
— President @vonderleyen.ec.europa.eu at the ‘Choose Europe for Science' event at La Sorbonne 🇫🇷
We will put forward a new 500 million package for 2025-2027 to support the best and the brightest researchers and scientists from Europe and around the world."
— President @vonderleyen.ec.europa.eu at the ‘Choose Europe for Science' event at La Sorbonne 🇫🇷
May 5, 2025 at 10:16 AM
"Science is an investment.
We will put forward a new 500 million package for 2025-2027 to support the best and the brightest researchers and scientists from Europe and around the world."
— President @vonderleyen.ec.europa.eu at the ‘Choose Europe for Science' event at La Sorbonne 🇫🇷
We will put forward a new 500 million package for 2025-2027 to support the best and the brightest researchers and scientists from Europe and around the world."
— President @vonderleyen.ec.europa.eu at the ‘Choose Europe for Science' event at La Sorbonne 🇫🇷
Reposted by William J Nicolas
Sad
This is an astonishing deliberate reversal of technological progress, the stuff Dark Ages are made of. www.nytimes.com/2025/05/01/u...
May 2, 2025 at 2:17 PM
Sad