Charles Bayly-Jones

New preprint from the Robertson Lab! We used AF ensemble generation for rigidity filtering with generative design to make cryoEM fiducials, enabling rapid inactive states of four drug targets and a beta2 extracellular fiducial to study GPCR activation!
www.biorxiv.org/content/10.6...

Construction of complex and diverse DNA sequences using DNA three-way junctions - Nature Sidewinder enables high-fidelity DNA assembly by separating the information that guides assembly from the final assembled sequence.

Nature research paper: Construction of complex and diverse DNA sequences using DNA three-way junctions

go.nature.com/4qu2ExZ

Not just biomedicine! Chemistry, physics, computer science, climate? Both ARC and NHMRC massively under funded. Success rates abysmal.

Skeptical of claim re budget increase by 250%? Aus R&D expenditure (%GDP) is stagnant, significantly below OECD average.

Inflation. Rising costs. USA exit. ?!?

First steps toward magnetic-elution affinity chromatographies, easily pattern surfaces, microfluidics, also probably cheaper than mag beads for robotic pipelines. Keen to see the data!

The latest research from our team is out in Cell @cp-cell.bsky.social! We used #cryo-EM, #imaging, #BRET, and #biosensors targeted to the lysosome to understand how the KICSTOR-GATOR1 complex turns off #mTORC1 in response to low levels of amino acids.

Excited to share our latest research, out today in Cell (@cellpress.bsky.social)

Using cryo-EM and cell-based studies, we reveal how large nutrient sensing protein complexes form at the lysosomal membrane to turn off mTORC1 and halt anabolic signalling.

Read the paper here: doi.org/10.1016/j.ce...

Most researchers miss out on innovation grants while medical fund sits on $25b Nine in 10 Australian researchers had their “ideas grant” applications rejected last year, even as Australia’s medical investment fund sits on $5 billion more than it was designed to hold.

The government can’t claim that medical research is a priority while failing to treat it as one. Nine in 10 leading researchers in Australia are missing out on government support for world‑class proposals, leaving exceptional talent uncertain about their future.

You're very kind to say so! Thanks Brett

Structure of the lysosomal KICSTOR-GATOR1-SAMTOR nutrient-sensing supercomplex This study reveals how KICSTOR and GATOR1 assemble into a crescent-shaped lysosomal complex that regulates mTORC1 during amino acid starvation and how SAMTOR binds KICSTOR in an S-adenosylmethionine-incompatible conformation to couple methionine sensing to mTORC1 regulation.

Now online! Structure of the lysosomal KICSTOR-GATOR1-SAMTOR nutrient-sensing supercomplex

Check out the manuscript for an exciting and unexpected finding!

👀

Here's an overview of the structure...

doi.org/10.1016/j.ce...

This figure captures how challenging the #cryoEM analysis was, but it doesn't capture the challenges we had to solve in molecular biology, biochemistry, purification, and functional testing. Every step was hard! So glad to see it available.

Thrilled to share our latest work @luptoncj.bsky.social @drellisdon.bsky.social @drmlhalls.bsky.social.

Structure of the lysosomal KICSTOR-GATOR1-SAMTOR nutrient-sensing supercomplex.

🧪🔬#cryoEM
Now online @cellpress.bsky.social.

doi.org/10.1016/j.ce...

AMAZING.

Amazing - thank you both - the annotation spread sheet on zenodo is exactly what I was looking for... very helpful resource :) 🙏

ODD & EVN if possible, I want to run isonet2 🙏

I kind of want to use the ones from the isonet2 paper, but again I'd rather not download and screen through them all just for three or four examples.

Crowd sourcing request!! I'm trialling some dev software and I'm looking for nice public tomograms to use as case studies. Downloading all tomos and looking for good examples is tedious. Can anyone recommend specific tomos from EMPIAR/CZI that have multiple STA targets?

#teamtomo #cryoEM

CryoEM folks, If you want to handle huge STAR file efficiently in Python, please try starfile-rs!

github.com/hanjinliu/star…

Reading a motion data of a particle from a 15 MB file is just like this ↓🤩

Interesting discussion. Pros/cons of PDFs vs digital objects.

As our standards increase, the burden of evidence will so too. These monster figs are a consequence. Why are we still held to prehistoric paper press page limits? Why not have as many ext. data figs as necessary? A PDF can be 100 pgs.

IsoNet2 determines cellular structures at submolecular resolution without averaging www.biorxiv.org/content/10.64898/2025.12.09.693325v1 #cryoEM

Wow! Congratulations Kiarash 🥳 super star. I'm sure I'm going to learn a lot from your work. Looking forward to it. Good luck!

Figure comparing runtime and VRAM utilization between Boltz-2 (baseline), and LMI4Boltz (+memory, and +chunk). Main plot: runtime (y-axis) versus token count (x-axis), showing that all methods scale similarly, with +memory and +chunk handling larger token counts. Inset scatterplot: PDB test lDDT scores from Boltz-2 versus LMI4Boltz, showing a strong linear correlation (values near y = x). Right panels: – Top bar chart: maximum tokens processable on a 24 GB GPU increase from 1596 (Boltz-2) to 2356 (+memory) and 2660 (+chunk). – Bottom bar chart: H200 runtime for 1596 tokens remains comparable across methods.

🧶🧬 We present LMi4Boltz:
www.biorxiv.org/content/10.1...

Boltz-2 is an excellent open source alternative to AlphaFold3. However, high VRAM use restricts modeling large complexes. Using careful memory management, we increase the Boltz-2 size limit by >60% while maintaining execution speed.

Awesome! Such good timing, I can use it today 😁😁 what's your opinion on CTF, better with or without?

Icecream: High-Fidelity Equivariant Cryo-Electron Tomography Cryo-electron tomography (cryo-ET) visualizes 3D cellular architecture in near-native states. Recent deep-learning methods (CryoCARE, IsoNet, DeepDeWedge, CryoLithe) improve denoising and artifact cor...

Our colleagues Vinith Kishore and Valentin Debarnot from the @ivandokmanic.bsky.social lab have come up with an amazing deep learning tool for denoising and filling the missing wedge in #cryoET data. I'm pleased to introduce Icecream🍧

End-to-end protein design in the browser through evedesign. Generate and interactively explore designs in 2D/3D and export them as codon-optimized DNA. The underlying open source framework (released soon) is build to easily add new methods, more on that soon.
🌐 evedesign.bio

Editors are also responsible. Anecdotally I have heard and experienced situations where reviewers provide very strong advice against publishing in current forms, yet this is ignored.

I guess… situations like this are where I really miss seeing the peer review file. Just baffling that this made the cut at Structure

My first thought is masked versus unmasked.

A bit like spiralling publication costs we need to start having a proper discussion around lab equipment servicing costs. These are often completely disproportionate to the cost of instrument and the service that is provided and seem to serve as a cash cow for vendors.