Michael Z. Lin | Lightnews

Michael Lin, MD PhD

@michaelzlin.bsky.social

2.7K followers 210 following 180 posts

Harvard → UCLA → HMS → UCSD → Associate Prof. of Neurobiology & Bioengineering at Stanford → Molecules, medicines, & SARSCoV2. Bad manners blocked.

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Michael Z. Lin is a Taiwanese-American biochemist and bioengineer. He is a professor of neurobiology and bioengineering at Stanford University. He is best known for his work on engineering optically and chemically controllable proteins. .. more

Neuroscience 42%

Biology 41%

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Michael Lin, MD PhD @michaelzlin.bsky.social · 10d

"Your idea might not work, unlike these other proposals using existing technology. So, lower score for approach."

(Gets it to work, submits proposal to use it...)

"You need to add Dr. X as co-PI. He's good at using existing tech on this question. He just got lots of $$$ for it actually"

Michael Lin, MD PhD @michaelzlin.bsky.social · 10d

The quote is from the founding documents of the BRAIN Initiative. Its support has allowed voltage imaging to attain performance levels predicted to be impossible not so long ago.

So thx to NINDS, NIMH, and NIH for investing in technology development!

obamawhitehouse.archives.gov/node/300741

Michael Lin, MD PhD @michaelzlin.bsky.social · 10d

The Lin Lab is excited to bring voltage imaging to #SfN2025!

On Tuesday we'll present new ASAP sensors for spikes and subthreshold potentials, showing how even simple equipment can record multi-unit electrical activity "at the speed of thought"

See you in San Diego @sfn.org!

Michael Lin, MD PhD @michaelzlin.bsky.social · 12d

That, and voltage indicators residing in a thin layer of membrane, is what makes voltage imaging inherently more challenging than calcium imaging, even when the voltage indicators provide more signal per event per molecule than calcium indicators (and they do)

Michael Lin, MD PhD @michaelzlin.bsky.social · 12d

The traces also illustrate well why you *must* image at 400 Hz or faster. The AP-induced ASAP4e transient only lasts for one frame (≤2.5 ms). If you image at 30 Hz (33 ms integration) then you'll average down the response to noise.

Michael Lin, MD PhD @michaelzlin.bsky.social · 12d

So calcium transients mask real spike patterns, and may give a misleading, or at least over-persistent, impression of how sub-second sensations or motions are encoded.

Michael Lin, MD PhD @michaelzlin.bsky.social · 12d

They also performed calcium imaging with GCaMP6f. This gives a nice comparison of how calcium and voltage differ in kinetics.

Essentially the entire voltage trace above (4 sec) would fit into one medium-sized calcium transient below.

Michael Lin, MD PhD @michaelzlin.bsky.social · 12d

The FOV is 0.38mm x 0.15mm, containing 19 labelled neurons. ASAP4e spikes had dF/F of 40% and SNR of 5.5 – 7.4.

The results show nicely that voltage recordings with ASAP4e aren't difficult. You just have to image at ≥400 frames per second.

Michael Lin, MD PhD @michaelzlin.bsky.social · 12d

Head-mounted 2-photon miniscope voltage imaging!

Weijian Yang's group at UC Davis sped up 2p scanning by multiplexing to achieve 400-Hz voltage imaging of ~20 neurons, using ASAP4e

These are the first freely moving single-cell voltage recordings as far as I know.

URL: www.cell.com/cell-reports...

High-speed neural imaging with multiplexed miniaturized two-photon microscopy

Zhang et al. develop two types of multiplexed miniaturized two-photon microscopes (M-MINI2Ps) that increase imaging speed via beam multiplexing while preserving spatial resolution and demonstrate thei...

www.cell.com

Michael Lin, MD PhD @michaelzlin.bsky.social · 20d

Actually they don't want to pay very much for them afterwards either

Michael Lin, MD PhD @michaelzlin.bsky.social · 20d

Somewhere in there: thinking, reading, analyzing, advising, listening, presenting, writing papers.

Might be easier for others. Choosing to specialize in technology development is selecting difficulty mode for grant-writing... people want the tools but they don't want to pay for them in advance.

Michael Lin, MD PhD @michaelzlin.bsky.social · 20d

Was up until 5:30 am writing a grant, then up again at 730 for another full day to finish it today. Now done! 🎉

As academics know, it's not one job. It might be 4. With funding rates at 5%, grant-writing is 1 full-time job. Then there's letters, reviews, committee work, teaching — endless deadlines

Reposted by Michael Z. Lin

Cornelius Gati @gati.bsky.social · 20d

Excited to share our latest @nature.com: How does naloxone (Narcan) stop an opioid overdose? We determined the first GDP-bound μ-opioid receptor–G protein structures and found naloxone traps a novel "latent” state, preventing GDP release and G protein activation.💊🧪 🧵👇 www.nature.com/articles/s41...

Reposted by Michael Z. Lin

Ming Tommy Tang @tommytang.bsky.social · 21d

A pan-KRAS inhibitor and its derived degrader elicit multifaceted anti-tumor efficacy in KRAS-driven cancers www.cell.com/cancer-cell...

Michael Lin, MD PhD @michaelzlin.bsky.social · 24d

No problem!

Michael Lin, MD PhD @michaelzlin.bsky.social · Oct 21

My daughter made a series of Halloween cats using air clay. Can you recognize them all?

Michael Lin, MD PhD @michaelzlin.bsky.social · Oct 4

Would you mind posting a link to the article; I couldn't find it. Thanks!

Michael Lin, MD PhD @michaelzlin.bsky.social · Sep 30

Had the pleasure of visiting Prague as part of an advisory commission for the Czech Academy of Sciences Institute of Biotechnology. Got to check out exciting science and the impressive ultra-high resolution MS machine.

Great to see people working hard to expand knowledge, with public support too!

Reposted by Marc Lynch, Nancy Kanwisher, Jesse M. Shapiro , and 6 more Marc Lynch, Nancy Kanwisher, Jesse M. Shapiro, Rosemary A. Joyce, American Library Association, Joseph Schafer, Juan Cole, Keith Head, Michael Z. Lin

Carl T. Bergstrom @carlbergstrom.com · Sep 20

I cannot overstate how remarkable it is that under GOP rule, US federal health regulations have been captured by fringe crackpots who espouse views that the vast majority of the US public—and nearly 100% of health professionals—reject.

Gift link:

Kennedy’s Vaccine Panel Votes to Limit Access to Covid Shots

www.nytimes.com

Michael Lin, MD PhD @michaelzlin.bsky.social · Sep 11

First clouds over Stanford since spring

Michael Lin, MD PhD @michaelzlin.bsky.social · Sep 6

I addressed this as well in the original thread. Thanks Christophe for linking to it

Michael Lin, MD PhD @michaelzlin.bsky.social · Aug 28

Thus the arbitrary 95% standard and how it is applied leads to contradictory conclusions, making scientists seem to hapless and clueless. So it harms public understanding and scientific support to insist on painting results in black or white rather than how they actually are: shades of gray.

Michael Lin, MD PhD @michaelzlin.bsky.social · Aug 28

And this is not just an academic exercise. How many times do you read in the news there is no association between risk factor X and outcome Y, only to read the opposite a few months later? These inconsistencies are often due to these Type 2 errors of declaring no difference when there was one.

Michael Lin, MD PhD @michaelzlin.bsky.social · Aug 28

It's more informative, accurate, and comprehensive than our current rules of saying yes or no when the answer is almost always different degrees of maybe. It would do justice to the concept of statistics, which is the supposed to be the science of quantifying degrees of certainty.

Michael Lin, MD PhD @michaelzlin.bsky.social · Aug 28

Then one can calmly and rationally consider whether that result provides some support for a hypothesis, together with what is mechanistically likely.

Again this would be for the 95% of non-clinical experiments that aren't addressing a hypothesis with treatment-chaning or financial implications.

Michael Lin, MD PhD @michaelzlin.bsky.social · Aug 28

This would be much more factual than "There was no significant difference between Groups A and B" or, even worse but too common, "There was no difference between Groups A and B".

Michael Lin, MD PhD @michaelzlin.bsky.social · Aug 28

Allow papers and proposals to show the graph of outcome distributions by condition and to state any possible or likely differences by the actual confidence level. For example, "Group B had 50% higher levels than Group A on average; the distributions were 90% likely non-random".

Michael Lin, MD PhD @michaelzlin.bsky.social · Aug 28

The defense of these arbitrary requirements is that they are necessary to prevent a high false-positive rate. But we don't have to generate a bunch of false negatives and throw out all discussion of actual likely differences to counteract that. There is a simple, easy, clear, and logical solution.

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