Ever felt constrained by the "4-color limit" in fluorescence imaging?

We use DNA-barcoded labeling to build high-plex panels, enabling imaging of 15 targets across the full fluorescence spectrum.

doi.org/10.64898/202...

Grateful to @sinemsaka.bsky.social and all authors for making this possible.

2026 essay competition

Oh wow. I know people here have THOUGHTS. Write them up & submit!!

I love that all essays have to be public before entering. This is exactly the type of conversation we need more of. (Also cash prizes + philanthropy is listening)

Now which on my list should I pick 🤔?

astera.org/essay-compet...

Alright people, re-upping this on your feed. Space is limited so please register soon!

www.neurosas.org/advanced-cou...

Start your independent as an ELISIR fellow right after your PhD, in one of the most terrific places in Europe !

Looks super cool! Is this type of co-culture prepared from separate animals/stages or from one preparation?

This #microscopymonday is a cleaning day. Watch how a #microglia cell mops up and phagozytoses debris and junk in a very messy neuronal co-culture. BTW, it was a proper cleaning job → the neurons made it and formed nice networks
Phase contrast imaging started at DIV1. One frame per 20 min.

All-at-once RNA folding with 3D motif prediction framed by evolutionary information - Nature Methods Structural RNAs exhibit a vast array of recurrent short three-dimensional (3D) elements found in loop regions involving non-Watson–Crick interactions that help arrange canonical double helices into tertiary structures. Here we present CaCoFold-R3D, a probabilistic grammar that predicts these RNA 3D motifs (also termed modules) jointly with RNA secondary structure over a sequence or alignment. CaCoFold-R3D uses evolutionary information present in an RNA alignment to reliably identify canonical helices (including pseudoknots) by covariation. Here we further introduce the R3D grammars, which also exploit helix covariation that constrains the positioning of the mostly noncovarying RNA 3D motifs. Our method runs predictions over an almost-exhaustive list of over 50 known RNA motifs (‘everything’). Motifs can appear in any nonhelical loop region (including three-way, four-way and higher junctions) (‘everywhere’). All structural motifs as well as the canonical helices are arranged into one single structure predicted by one single joint probabilistic grammar (‘all-at-once’). Our results demonstrate that CaCoFold-R3D is a valid alternative for predicting the all-residue interactions present in a RNA 3D structure. CaCoFold-R3D is fast and easily customizable for novel motif discovery and shows promising value both as a strong input for deep learning approaches to all-atom structure prediction as well as toward guiding RNA design as drug targets for therapeutic small molecules.

Integrated prediction of RNA secondary structure jointly with 3D motifs and pseudoknots guided by evolutionary information.
@aakaran31.bsky.social and @rivaselenarivas.bsky.social

link.springer.com/article/10.1...

A deep learning pipeline for accurate and automated restoration, segmentation, and quantification of dendritic spines Garcia et al. present RESPAN, a pipeline that enables automated dendritic spine analysis through seamless integration of deep learning image restoration and segmentation capabilities with comprehensiv...

Excited to highlight a new paper from my graduate student Sergio Bernal Garcia who, together withLuke Hammond, developed RESPAN, a new deep-learning pipeline automating the segmentation of neuronal morphology and dendritic spines from fluorescent microscopy images:
www.cell.com/cell-reports...

🧠🦈Excited to present our latest work🧠🦈Interested in brain evolution? And shark embryos? Then read on… Our work sheds light on the deep origins of our brain’s most complex regions.

A proteome-wide screen for membrane-interactions in intrinsically disordered regions of transmembrane proteins reveals a role in disease Transmembrane proteins mediate essential cellular processes including signaling, transport, and ion flux. Besides their well-characterized structured domains, most contain intrinsically disordered reg...

A proteome-wide screen for membrane-interactions in intrinsically disordered regions of transmembrane proteins reveals a role in disease www.biorxiv.org/content/10.1...

Brain Surfaces of 70 primate species

1
To predict the behaviour of a primate, would you rather base your guess on a closely related species or one with a similar brain shape? We looked at brains & behaviours of 70 species, you’ll be surprised!

🧵Thread on our new preprint with @r3rt0.bsky.social , doi.org/10.1101/2025...

Love this!

Tooting my own horn here, but if you’re interested in some of the practical considerations mentioned at the end of the article, you can check out this perspective from earlier in my postdoc: www.cell.com/neuron/fullt...

Graphical abstract for "Vocal communication is seasonal in social groups of wild, free-living house mice." The abstract has, from top to bottom, a title, four middle image panels, and two bottom text panels. Image title: "Vocal communication in social groups of wild-free living house mice" Middle image panels from left to right: (1) An aerial snap shot of the region where the study site is located, an agricultural landscape in rural Switzerland. (2) An image of the study site, a small barn in the forest inhabited by mice. (3) An image of a radio frequency identification (RFID) box used to track mouse social interactions. A mouse is entering the box from the left while another sits outside. (4) A spectrogram showing example vocalizations - one low frequency squeak and one ultrasonic call - recorded from an RFID box. Bottom panels: Left: Data Collection  - 10 years of RFID-based tracking data (from 6,946 mice) - 15 months of acoustic monitoring (totaling 6,594 hours) - Machine learning for vocal detection and labeling (CNN) Right: Key Findings - Vocalization is seasonal (most in spring and summer) - Vocalization is associated with the presence of pups - Vocalization is correlated with social group dynamics

Very happy to share the latest from my postdoc‬!

10 yrs of mouse social networks + 1.25 yrs of acoustic data ➡️ insight into vocalization & sociality in a wild population of your favorite lab model 🐁

paper: bit.ly/4n93yyD
data: bit.ly/4lfFBEk
code: bit.ly/4kNnMwx

#bioacoustics #neuroskyence

1/8

It’s a quill? A sea pen? No—it’s a gill filament! 🪶🪸🐟

Under the microscope, this fish gill structure looks just like a sea pen.
Fascinating how nature keeps circling back to the same shapes.

Want to learn how gills develop?
👉 www.biorxiv.org/content/10.1...

#FluorescenceFriday #Zebrafish

Brightly labelled pyramidal cells in the mouse retrosplenial cortex. Blood vessels are visible of various thicknesses in darker colours.

#neuroskyence folks: as my postdoc grant is running out soon, I am looking for new opportunities in systems neuroscience!

Keywords: patch clamp ephys, opto, mouse behavior, (in vivo) voltage imaging. Would love to return to the Basal Ganglia.

Sharing appreciated, and happy #FluorescenceFriday !

Advertisement for PhD position

My lab at @ethzurich.bsky.social is looking for a motivated PhD student. We develop chemical tools for advanced fluorescence microscopy 🔬 and work at the interface of synthetic chemistry ⚗️ and protein engineering 🦠. Sharing with skilled Master students appreciated. More info at tinyurl.com/2dbjk5ty

🚨iGluSnFR4 is finally out!🚨🧪

We present iGluSnFR4f and 4s, a novel pair of genetically-encoded glutamate indicators designed for high-fidelity imaging of synaptic activity in the living brain. ⬇️

www.biorxiv.org/content/10.1...

🎥 Below: iGluSnFR4s detecting minis in cultures w/ TTX

#Neuroscience

eSylites: Synthetic Probes for Visualization and Topographic Mapping of Single Excitatory Synapses The spatiotemporal organization of the postsynaptic density (PSD) is a fundamental determinant of synaptic transmission, information processing, and storage in the brain. The major bottleneck that prevents the direct and precise representation of the nanometer-scaled organization of excitatory glutamatergic synapses is the size of antibodies, nanobodies, and the genetically encoded fluorescent tags. Here, we introduce small, high affinity synthetic probes for simplified, high contrast visualization of excitatory synapses without the limitations of larger biomolecules. In vitro binding quantification together with microscopy-based evaluation identified eSylites, a series of fluorescent bivalent peptides comprising a dye, linker, and sequence composition that show remarkable cellular target selectivity. Applied on primary neurons or brain slices at nanomolar concentrations, eSylites specifically report PSD-95, the key orchestrator of glutamate receptor nanodomains juxtaposed to the presynaptic glutamate release sites that mediate fast synaptic transmission. The eSylite design minimizes a spatial dye offset and thereby enables visualization of PSD-95 with improved localization precision and further time-resolved discrimination. In particular, we find that individual dendritic spines can contain separate nanodomains enriched for either PSD-95 or its closest homologues, PSD-93 or SAP102. Collectively, these data establish eSylites as a broadly applicable tool for simplified excitatory synapse visualization, as well as a high-end microscopy compatible probe for resolving the PSD organization with unprecedented resolution.

🚀 Excited to share our latest work in #JACS on eSylites!

—Synthetic, high-affinity #ChemicalBiology probes for #SuperResolution #Synapse visualization & precise mapping in neurons and brain slices—without the need for antibodies, tags, or transfection!

📢 Read more: pubs.acs.org/doi/10.1021/...

Crick BioImage Analysis Sympsoium Logo

Calling all...
🔬 Microscopists
💻 BioImage Analysts
👩‍🔬 Life Scientists

📅 Save the Date

The 5th edition of the Crick BioImage Analysis Symposium will take place on November 24/25th 2025.

More details to follow...

#CBIAS2025

How to communicate the value of curiosity-driven research The burden of proof is on us, as researchers, to explain why what we do is valuable to society.

We must learn to showcase the practical significance of basic research, demonstrating how seemingly arcane investigations yield transformative applications, writes @tonyzador.bsky.social www.thetransmitter.org/outreach/how...

RNA-binding proteins and glycoRNAs form domains on the cell surface for cell-penetrating peptide entry Mammalian cells present RNA-binding proteins on the cell surface that form clustered domains containing glycoRNAs.

#RBPs and #glycoRNAs are amazing! Congrats! Great work!
#RNA #RNAsky

RNA-binding proteins and glycoRNAs form domains on the cell surface for cell-penetrating peptide entry: Cell www.cell.com/cell/fulltex...

Peroxisomal core structures segregate diverse metabolic pathways - Nature Communications Peroxisomes contain detergent resistant core structures. Bäcker et al. show that these core structures contain diverse enzymes and serve to enable metabolic compartmentalization of the peroxisome lume...

nature.com/articles/s41467-025-57053-9
Finally this work is out - we show that short sequence motifs direct proteins to specific peroxisomal sub-domains. Fantastic collaboration with @bangebalcony.bsky.social , Johannes Freitag @unimarburg.bsky.social and many more! @uio.no @cancelluio.bsky.social

How energy determines spatial localisation and copy number of molecules in neurons - Nature Communications Various factors can be involved in the quantities of mRNAs and proteins in neurons. In this study, the authors show that the drive to save energy determines transcript quantities and their location wh...

#Spatialbiology
www.nature.com/articles/s41...

Making intrabodies from antibodies just got easier! Learn how we made 𝟭𝟵 intrabodies to bind and light up peptides and histone modifications in live cells. And thanks to Academia, all sequences are freely available. (video credit: Yuko Sato @YukoSatoT2) (1/15)
www.biorxiv.org/content/10.1...

Schematic overview on how MicroSpit operates. It can split superimposed structures in fluorescent image channels by using a suitably trained AI.

Concrete example for how MicroSplit unmixes four superimposed structures.

Immagine you could image two cellular structures in the same fluorescent channel and still reliably get them separated afterwards…
What would you do with this?

Now… what would you do if that also worked with 4 structures at once? 👇 #MicroSplit #preview🧵

Protein codes promote selective subcellular compartmentalization Cells have evolved mechanisms to distribute ~10 billion protein molecules to subcellular compartments where diverse proteins involved in shared functions must assemble. Here, we demonstrate that proteins with shared functions share amino acid sequence ...

Protein codes promote selective subcellular compartmentalization | Science www.science.org/doi/10.1126/...

Home This site contains the complete version of the Fiji Training Manual that is written and maintained by Cameron Nowell of the Monash Institue of Pharmaceutical Science. This manual is provided under the...

Answering the call of @haesleinhuepf.bsky.social, Christian Tischer, Pete Bankhead, @kbias.bsky.social @bethcimini.bsky.social
My Fiji training notes are now FAIR. All online in an open format to download and use for teaching and training. All in Google Doc or PDF formats
bit.ly/4hkfEBF

A portrait of Daisy Roulland-Dussoix from Wikipedia: https://en.wikipedia.org/wiki/Daisy_Roulland-Dussoix

Do you know Daisy Roulland-Dussoix? She is one of the discoverers of restriction enzymes, who’s findings paved the way for the development of recombinant DNA and cloning technologies. Accordingly, the finding was rewarded with a #NobelPrize. But the prize didn’t go to her.
🧵👇

A pyramidal neuron from the prefrontal cortex. #microscopymonday
Labelled with DiI, imaged with the FV3000 CLSM, & depicted using @kwolbachia.bsky.social new KTZ_bw_kawa LUT.

There are new stable red fluorescent proteins coming, but organic fluorophores are fighting back! Impressive photostability of Phoenix Fluor 555 for live-cell imaging with HaloTag, just out in @naturemethods.bsky.social:
doi.org/10.1038/s415...