Super-resolution microscopes reveal new details of cells and disease | Hacker News Reader

Super-resolution microscopes reveal new details of cells and disease

knowablemagazine.org

82 pointsrbanffy13 comments

I love when I come across something super niche on HN where I actually know someone working in it. A friend of mine from college (university), Ibrahim Cissé, now runs a lab[0] in this space, and while the description of his work is way over my head, I imagine some of you might find it interesting:

> Laboratory Ibrahim Cissé > Single Molecule and Super-Resolution imaging in live cells > We leverage expertise in Single-Molecule and Super-Resolution imaging in live cells to study collective behaviors (e.g., protein clustering) emerging from weak or transient biomolecular interactions in mammalian cells. We unveil, often for the first time, that these clusters exist in living cells, and we expand both on the imaging approaches and the cellular and molecular biology techniques to discover the biophysical mechanisms of action and their function in vivo.

Or for a quick layman's explanation, here's a YouTube video of him describing his work when he won a MacArthur Fellowship [1].

I'm grateful for HN for reminding me of him and giving me an excuse to look up his work a little more in-depth.

[0]: https://www.ie-freiburg.mpg.de/cisse

[1]: https://www.youtube.com/watch?v=iXYof3RQ_WU

“runs a lab” is putting it lightly. He’s a Max Planck institute director. This means essentially limitless funds for his own research and can shape hiring of faculty in his institute.

Haha fair, I think I thought the Max Planck role was prestigious but 1) didn't know what it entailed and 2) maybe feared to almost boast about knowing such a cool person.

Thank you for saying that and helping me better understand what it means.

Sorry for being a bit off-topic. Biology wasn't my forte in high school, I wish I had read this article back then https://jsomers.net/i-should-have-loved-biology/ and seen that video (9:08 min) https://youtu.be/WFCvkkDSfIU?si=12bbZajsUnYagD4_&t=15

This looks really good, thanks for sharing!

There are biotech companies like Eikon Therapeutics (https://www.eikontx.com/ ) where super-resolution microscopy in living cells is a central part of the platform.

There is also one widespread approach that isn't mentioned in the article: expansion microscopy. Expansion takes the scifi-sounding approach of: what if you could make your sample physically bigger? See the Wikipedia page for more: https://en.wikipedia.org/wiki/Expansion_microscopy

Couple more notes:

1. Stephen Hell has been theorizing about how to do super-res microscopy since the mid-90s, so the article saying it was sci-fi "20 years ago" is off by about 10 years.

2. Stephen Hell has recently given the world another new technique, MINFLUX, which seems to be his best gift to super-res researchers so far. :)

That’s a very good magazine iirc. I discovered it during the pandemic and remember how stunned i was that i had been unaware of such a high quality science magazine. Thanks for reminder that i should drive by this website more often.

> As the probes twinkle on and off, computational models estimate exactly where each molecule is located — and reconstruct a high-resolution image of the sample.

How do time and motion fit in with these techniques? I'm dimly aware that the molecular machinery inside cells moves pretty fast, and that a lot of things move around randomly. In normal size ranges that kind of thing would naturally make it hard to get a clear picture. Do these imaging techniques require that stuff be frozen or specially prepared? Or do the techniques themselves work so fast that they can get a snapshot regardless?

Yes. This isn't for dynamic events.

The cells are "fixed" (with paraformaldehyde (PFA) for example), so yes these are snapshots but not because the technique is fast. These techniques can actually be quite slow because you need to collect enough blinks to reconstruct the final image.

You can track things in live cells with MINFLUX, one of the recent super-resolution techniques coming from Stefan Hell's lab. Edit: add MINFLUX review: https://arxiv.org/pdf/2410.15902

Other commenters are wrong. Live-cell can be done with older single-molecule localization microscopy using techniques like PAINT. The fluorophore is usually strategically added in a way that binding-unbinding events cause excitation. Algorithms can then infer identity of single fluorophores based on their excitation pattern/strength and can predict whether it's two distinct fluorophore molecules or the same molecule moving over multiple frames of image acquisition.

Reply on news.ycombinator.com