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Matt Lycas

@lycasworks

Neuroscientist and Super-Resolution Microscopist

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22.12.2024
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Latest posts by Matt Lycas @lycasworks

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All set for some expanding

09.02.2026 23:35 πŸ‘ 7 πŸ” 0 πŸ’¬ 1 πŸ“Œ 0
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πŸ§ͺ We are excited to share this novel open access paper on Phasor Mixing Coefficient to analyze colocalization, developed by folks @i2janelia.bsky.social and @aicjanelia.bsky.social. This is also the first technical paper jointly published with our sister imaging center @malacridalab.bsky.social!

28.01.2026 16:20 πŸ‘ 45 πŸ” 21 πŸ’¬ 2 πŸ“Œ 2
Quantitative Expansion Microscopy for In Situ Estimation of Endogenous Target Abundance Spatially mapping protein abundance in situ can offer important insights into molecular mechanisms and the physiological functions of protein complexes. This is typically achieved by combining super-resolution microscopy to image fluorescently-labeled protein locations with statistical estimators to retrieve abundances, where accuracy is strongly impacted by labeling efficiency. We introduce quantitative expansion microscopy (qExM) as a method to estimate endogenous protein abundance on ExM data, which offers improved antibody targeting through molecular decrowding. Using cryo-fixation, we preserved ultrastructure and enhanced labeling efficiency to improve accuracy in abundance estimations. We benchmark the effectiveness of qExM by quantifying the stoichiometry of well-characterized nuclear pore complex subunits, and find a mean percent error of 9.4%. We further apply qExM to investigate the abundance of mitochondrial respiratory chain complexes in functionally distinct organelle subpopulations, and of mitochondrial respiratory chain super-complexes in differentially activated human T-cells. qExM provides a robust methodological framework for quantifying endogenous protein abundance in expanded samples in situ. ### Competing Interest Statement The authors have declared no competing interest. Swiss National Science Foundation, https://ror.org/00yjd3n13, 310030_215737 International Human Frontier Science Program Organization, https://ror.org/02ebx7v45, RGP0038/2021 European Research Council, CoG 819823 Piko

www.biorxiv.org/content/10.6...

20.01.2026 17:41 πŸ‘ 4 πŸ” 0 πŸ’¬ 0 πŸ“Œ 0

You rock!! Sorry bout that thanks!

20.01.2026 17:29 πŸ‘ 1 πŸ” 0 πŸ’¬ 1 πŸ“Œ 0

Found the unbroken link:

www.biorxiv.org/content/10.6...

20.01.2026 17:26 πŸ‘ 3 πŸ” 1 πŸ’¬ 1 πŸ“Œ 1

@lycasworks.bsky.social developed quantitative expansion (qExM) to estimate endogenous protein quantities in situ. His ExM protocols offer epitope preservation and accessibility so that standard Western Blot antibodies can be used. Also, check out the cristae, supercomplexes, specialized mitos 🀩

20.01.2026 16:48 πŸ‘ 26 πŸ” 4 πŸ’¬ 1 πŸ“Œ 0

🎸Why this is exciting!!πŸ¦–

Quantitative super-resolution often requires genetically encoded tags to get labeling sufficient for quantitative imaging. Here with qExM we use commercial antibodies for endogenous targets.

This opens HUGE opportunities to count in tissues, organisms, or clinical samples!

20.01.2026 16:27 πŸ‘ 2 πŸ” 1 πŸ’¬ 0 πŸ“Œ 0

We then used qExM to measure the abundance of mitochondrial respiratory chain complexes in situ!

We measured the abundances for Complex I, III, and IV.

How they differ in absolute abundances in metabolically distinct subpopulations

And even how T-cell activation changes supercomplex density

20.01.2026 16:24 πŸ‘ 2 πŸ” 2 πŸ’¬ 1 πŸ“Œ 0

We validated qExM first on nuclear pore complexes, attempting to quantify the 8 fold symmetry without using this prior knowledge.

We achieved a mean error of just 9.4% πŸ˜πŸ”¬πŸŽΈ

With these tools in place we moved to tackle protein complex abundances that were unknown....

20.01.2026 16:19 πŸ‘ 6 πŸ” 1 πŸ’¬ 1 πŸ“Œ 0

How does qExM work?

We use cryo-fixation + GMA anchoring to boost antibody labeling efficiency, then apply capture-recapture statistics to dual-labeled samples.

The expansion makes epitopes more accessible while reducing label size relative to targets - perfect for quantitative imaging!

20.01.2026 16:15 πŸ‘ 3 πŸ” 1 πŸ’¬ 1 πŸ“Œ 0

Thank you to our amazing group for this project
@sulianamanley.bsky.social
@kmdouglass.bsky.social
@jclandoni.bsky.social
@tittanoferi.bsky.social
@zimmerli.bsky.social

20.01.2026 16:14 πŸ‘ 2 πŸ” 0 πŸ’¬ 1 πŸ“Œ 0

πŸ”¬πŸš¨New preprint alert! πŸš¨πŸ”¬

We developed quantitative expansion microscopy (qExM) - a method to accurately count proteins in situ by combining expansion microscopy's improved labeling with statistical estimators borrowed from ecology

www.biorxiv.org/content/10.6...

#SuperResolution #CellBiology

20.01.2026 16:12 πŸ‘ 44 πŸ” 18 πŸ’¬ 5 πŸ“Œ 1
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Quantitative Imaging: From Acquisition to Analysis Cold Spring Harbor Laboratory Meetings & Courses -- a private, non-profit institution with research programs in cancer, neuroscience, plant biology, genomics, bioinformatics.

PIs & Group Leaders, do your trainees need to learn light microscopy and image analysis? Send them to us! Financial aid is available! Applications due Friday 1/30. meetings.cshl.edu/courses.aspx...

14.01.2026 16:20 πŸ‘ 23 πŸ” 16 πŸ’¬ 0 πŸ“Œ 4
Introduction - Microscopy Basic Training

I finally got around to writing the discussion section of our lab's basic training course on live cell #microscopy. I explain the tradeoffs involved in designing an imaging experiment and the art of thinking of the experiment as an optimization problem.

leb-epfl.github.io/basic_traini...

13.01.2026 15:07 πŸ‘ 14 πŸ” 4 πŸ’¬ 1 πŸ“Œ 0
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Quantitative Imaging: From Acquisition to Analysis Cold Spring Harbor Laboratory Meetings & Courses -- a private, non-profit institution with research programs in cancer, neuroscience, plant biology, genomics, bioinformatics.

πŸ”¬ πŸ–₯️ Applications are open for the CSHL course Quantitative Imaging: From Acquisition to Analysis (April 6–21, 2026)!

An intensive, hands-on course covering advanced fluorescence microscopy and quantitative image analysis using open-source tools.

πŸ—“οΈ Apply online by Jan 30, 2026

06.01.2026 19:18 πŸ‘ 44 πŸ” 32 πŸ’¬ 1 πŸ“Œ 2

Definitely alien πŸ‘½

05.01.2026 16:51 πŸ‘ 1 πŸ” 0 πŸ’¬ 0 πŸ“Œ 0
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Seal taking a nap off the coast of Cape Town

05.01.2026 09:30 πŸ‘ 3 πŸ” 0 πŸ’¬ 0 πŸ“Œ 0
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A super detailed protocol + video on Cryo-ExM - Cryo-Expansion Microscopy, led by the labs of our former postdocs @marinelap.bsky.social & @ebertiaux.bsky.social.
Clear, practical, and very useful for anyone doing nanoscale imaging πŸš€ app.jove.com/t/68595/expa...

25.12.2025 13:41 πŸ‘ 126 πŸ” 32 πŸ’¬ 0 πŸ“Œ 1
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✨ Blinking #nanobodies that work for single-molecule localization πŸ”¬
Our new preprint shows that the self-blinking dye JF635b restores robust, buffer-free blinking in #nanobodies, enabling reliable #dSTORM, #MINFLUX, and more, without chemical-switching buffers. Opening new possibilities for #ExM!

22.12.2025 10:45 πŸ‘ 76 πŸ” 19 πŸ’¬ 3 πŸ“Œ 2

Thrilled to see our review article "The evolutionary origins of synaptic proteins" highlighted on the cover of Nature Reviews Neuroscience 🀩.

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

@msarscentre.bsky.social 🧠✨🧬🌊πŸͺΌπŸ§½

17.12.2025 15:25 πŸ‘ 120 πŸ” 37 πŸ’¬ 1 πŸ“Œ 2
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Membrane-associated periodic skeleton regulates major forms of endocytosis in neurons through a signaling-driven positive feedback loop Endocytosis enables neurons to internalize molecules, maintaining homeostasis and responsiveness. The neuronal membrane-associated periodic skeleton (MPS), an actin-spectrin-based cytoskeletal lattice...

New preprint showing how the membrane-associated periodic skeleton (MPS) restricts endocytosis in neurons: www.biorxiv.org/content/10.6...
It nicely confirms our work from last year (science.org/doi/10.1126/science.ado2032) and extends it to other compartments in more mature neurons

17.12.2025 11:48 πŸ‘ 30 πŸ” 10 πŸ’¬ 2 πŸ“Œ 0
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New paper from @zhixingchen2.bsky.social's lab!

It turns out that, in addition to its very low phototoxicity, PKmito Deep Red (PKMDR) directly reports on mitochondrial membrane potential (MMP) in live cells through its lifetime!

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

16.12.2025 12:11 πŸ‘ 53 πŸ” 19 πŸ’¬ 4 πŸ“Œ 1

πŸ₯³πŸ₯³πŸ₯³

10.12.2025 15:05 πŸ‘ 1 πŸ” 0 πŸ’¬ 0 πŸ“Œ 0
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FLIM at the Biozentrum πŸ”¬

08.12.2025 12:39 πŸ‘ 1 πŸ” 0 πŸ’¬ 0 πŸ“Œ 0

Absolutely, I will!

05.12.2025 12:18 πŸ‘ 1 πŸ” 0 πŸ’¬ 0 πŸ“Œ 0

NHS ester, but I got some post expansion immunolabeling working on the tardigrades I’ll post once I return from this travel

05.12.2025 11:42 πŸ‘ 0 πŸ” 0 πŸ’¬ 1 πŸ“Œ 0
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Tardigrades looking BIG

27.11.2025 20:15 πŸ‘ 5 πŸ” 0 πŸ’¬ 0 πŸ“Œ 0
The Company of Biologists 100 logo to the left and QR code to the right.
 
Portrait of Jennifer Waters to the left, text to the right
 
100 extraordinary biologists

Jennifer Waters

Jennifer Waters, a FocalPlane Scientific Advisory Board member, is the Director of Core for Imaging Technology & Education, Harvard Medical School, USA. She created MicroList and draws on over 25 years of teaching experience to create accessible microscopy education resources, including the online platform Microtutor.

#100biologists #biologists100

The Company of Biologists 100 logo to the left and QR code to the right. Portrait of Jennifer Waters to the left, text to the right 100 extraordinary biologists Jennifer Waters Jennifer Waters, a FocalPlane Scientific Advisory Board member, is the Director of Core for Imaging Technology & Education, Harvard Medical School, USA. She created MicroList and draws on over 25 years of teaching experience to create accessible microscopy education resources, including the online platform Microtutor. #100biologists #biologists100

We are highlighting Jennifer Waters, a @focalplane.bsky.social Scientific Advisory Board member, Director of CITE, Harvard Medical School, and creator of MicroList (now featured in FocalPlane) and Microtutor, as an extraordinary biologist. #100biologists
@jencwaters.bsky.social

26.11.2025 09:33 πŸ‘ 31 πŸ” 8 πŸ’¬ 0 πŸ“Œ 3
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14.11.2025 13:32 πŸ‘ 4 πŸ” 0 πŸ’¬ 0 πŸ“Œ 0
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Expansion microscopy of a tardigrade I caught outside with the objective I got on eBay

14.11.2025 13:22 πŸ‘ 15 πŸ” 0 πŸ’¬ 2 πŸ“Œ 0