This work was made possible by amazing collaborators including @biedererlab.bsky.social, Tony Koleske, James Rothman, @pdc-lab.bsky.social, Gary Desir, Xinran Liu, and funding from NIH, @wellcometrust.bsky.social, @kavliatyale.bsky.social, Brain Research Foundation, Shank2 Foundation. (5/5)
X-rays can resolve ultrastructure - milestone for ultrastructure imaging w/o cutting. Thanks to an amazing team -
@carlesbosch.bsky.social
@adrianawanner.bsky.social
Ana Diaz and collaborators
@crick.ac.uk
@psich.bsky.social and
@esrf.fr
and funders
@wellcometrust.bsky.social
@ukri.org
Indeed, we show that "pan-ExM" enables tracing of the thinnest neuronal wires (spine necks and thin axons) and can be scaled up to produce connectomes. Combining with antibody labeling enables “molecular connectomics”, which can unite cellular/molecular and systems understandings of the brain. (4/5)
We developed a "pan-expansion" protocol that works well in brain tissue, using a ~20x iterative expansion compatible with pan-protein and lipid stains to reveal dense, nanoscale ultrastructure of neuronal circuits (~20 nm effective resolution) with a confocal microscope. (2/5)
Because this protocol retains proteins in the gel, it is natively compatible with antibody labeling, allowing localization of synaptic proteins, cell-type and subcellular markers with ultrastructural resolution, effectively a sort of “multicolor electron microscopy”. (3/5)
Our new paper showcasing molecular connectomics with pan-expansion microscopy is out in @natbiotech.nature.com! www.nature.com/articles/s41...
This wonderful collaboration with @bewersdorflab.bsky.social was led by Ons M'Saad (now founder/CEO of Panluminate) and @allisonphysics.bsky.social. (1/5)
Connectomics is Method of the Year 2025!!
@natmethods.nature.com
just released the news nature.com/articles/s41... In my perspective piece, I afford some predictions into the future and compare how we are doing vs. genomics www.nature.com/articles/s41...
#paper!
X-rays can resolve #ultrastructure in tissues non-destructively.
www.nature.com/articles/s41...
Shoutout to key collaborators at @crick.ac.uk and @psich.bsky.social Ana Diaz, @adrianawanner.bsky.social and @andreas-t-schaefer.bsky.social, and to the whole team that made this possible.
Our Method of the Year 2025 is...drumroll please...EM-based connectomics!!
Our Editorial introduces our choice and highlights six Comments and other related content in this special issue. Please join us in celebrating EM-based connectomics! 🎉🧠🔬
www.nature.com/articles/s41...
Happy to share the first paper from my journey at @psich.bsky.social towards X-ray connectomics, now out in @natmethods.nature.com: www.nature.com/articles/s41...
