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Alex Naka @gottapatchemall.bsky.social · 8d

thanks!!

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Alex Naka @gottapatchemall.bsky.social · 8d

it's been seriously inspiring to watch the progress on this, E11 is kicking ass

Andrew Payne @andrewcpayne.bsky.social · 8d

E11 Bio is excited to unveil PRISM technology for mapping brain wiring with simple light microscopes. Today, brain mapping in humans and other mammals is bottlenecked by accurate neuron tracing. PRISM uses molecular ID codes and AI to help neurons trace themselves.

Read more: e11.bio/blog/prism

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Reposted by Alex Naka

Andrew Payne @andrewcpayne.bsky.social · 8d

E11 Bio is excited to unveil PRISM technology for mapping brain wiring with simple light microscopes. Today, brain mapping in humans and other mammals is bottlenecked by accurate neuron tracing. PRISM uses molecular ID codes and AI to help neurons trace themselves.

Read more: e11.bio/blog/prism

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Reposted by Alex Naka

BejaLab @bejalab.bsky.social · 21d

I LOVE their curtain test!!

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Ofer Yizhar @oyiz.bsky.social · 21d

Really cool stuff! Engineered excitatory opsins responding to 15nW light

BejaLab @bejalab.bsky.social · 21d

WAChRs are excitatory opsins sensitive to indoor lighting www.biorxiv.org/content/10.1...

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Alex Naka @gottapatchemall.bsky.social · 21d

Combining with something like a commercially available AR headset is also probably a good direction - something patient friendly that still allows control over statistics of visual input

Alex Naka @gottapatchemall.bsky.social · 21d

Great question, the short answer is no I do not.

There are some avenues here though e.g. coexpress with another less sensitive channelrhodopsin. And I guess if you have to choose between attenuating or amplifying light from the environment, it’s easier to attenuate

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Alex Naka @gottapatchemall.bsky.social · 21d

But it might be something to do with our transfection protocol - we’ve been hesitant to put too much time into optimizing there since there are many degrees of freedom and we knew just using AAV would solve things

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Alex Naka @gottapatchemall.bsky.social · 21d

Thanks! I’m fortunate to work with people who will basically run through walls to get data

Re AAV vs lipofection - best guess is that it’s to do with higher and more variable copy number from lipofection; seems like it’s easy to make cells unhappy when lipofecting certain opsins in

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Alex Naka @gottapatchemall.bsky.social · 21d

Tremendous effort by some very talented people: Amanda Tose, Alberto Nava, Sara McGrath, and @mardinly, among many others

This lowercase science is brought to you by uppercase Science
science.xyz/news/new-fr...

Opening New Frontiers in Optogenetic Research, Sensitive Proteins Respond to Ambient Light | Science Corporation

Science Corporation is a clinical-stage medical technology company.

science.xyz

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Alex Naka @gottapatchemall.bsky.social · 21d

We have a ton of fun details and other results that didn't make it into here, but we'll be dropping more soon.

Please send thoughts/feedback. And holler at us if you want to try WAChRs out for your own experiments, we'll send you some

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Alex Naka @gottapatchemall.bsky.social · 21d

We also did a low-tech experiment we call the curtain test. It's basically peekaboo: cover the rig with a curtain for a while, then open it again. WAChRs respond pretty well.

Simple - but a sanity check for being able to do something like optogenetic vision restoration.

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Alex Naka @gottapatchemall.bsky.social · 21d

In particular, WAChRs can drive decent photocurrents with very low intensity light.

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Alex Naka @gottapatchemall.bsky.social · 21d

We picked three finalists that offer a trade-off between speed and sensitivity: WAChR-f/m/s

We benchmarked these against some existing optogenetic tools on our manual patch clamp rig ("Patchrig Swayze").

We think they offer superior performance for a lot of applications.

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Alex Naka @gottapatchemall.bsky.social · 21d

We kept Mr. Patchino very busy while we iteratively searched for improvements - several hundred new WAChR variants for this project (and 1750+ so far in our broader campaign).

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Alex Naka @gottapatchemall.bsky.social · 21d

We ran an ML-guided directed evolution campaign to optimize WAChR. To do this, we developed a system that uses automated patch clamp to quickly screen opsin functional properties.

(We named him Al Patchino)

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Alex Naka @gottapatchemall.bsky.social · 21d

We used the K+ selective opsin WiChR as a starting point pmc.ncbi.nlm.nih.gov/articles/PM...

WiChR is a strong, sensitive optogenetic silencer. We applied a mutation that breaks K+ selectivity, which converts it into an excitatory channel. We call this mutant WAChR (pronounced "watcher").

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Alex Naka @gottapatchemall.bsky.social · 21d

Preprint here
www.biorxiv.org/content/10....

Short thread below

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Alex Naka @gottapatchemall.bsky.social · 21d

My group at Science has been running a big campaign to engineer new channelrhodopsins.

Excited to share the first results from it today: a suite of highly sensitive new opsins.

We call them "WAChRs".

Everyday indoor office lighting is enough to activate them pretty strongly.

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Reposted by Alex Naka

Hideaki E. Kato @emekato.bsky.social · 21d

Happy to share our new preprint on the red-shifted channelrhodopsin ChR024, recently discovered by Inoue Lab (biorxiv.org/content/10.1...
), highlighting its long-wavelength absorption and ion conductance:
biorxiv.org/content/10.1...

Many thanks to our wonderful lab members and collaborators!

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Reposted by Alex Naka

lacey @byelacey.bsky.social · Jun 24

mac is here on this #makeaterriblecomicday2025 to school you all in THREAT MANAGEMENT SYSTEMS do not get caught off guard or Who Knows What Might Happen

a six panel comic titled "threat management: the complete guide". each panel is a hastily drawn white dog with large jowls detailing the steps on how to bark at things.

panel 1: step 1: scan all known dimensions. (the dog is staring into the middle distance, eyes seemingly going in different directions, while the background is reminiscent of the space odyssey stargate scene)

panel 2: lock in. (the dog's face is drawn in close up, biting his lip and growling)

panel 3: sound the alarm (the dog is barking, jowls flapping)

panel 4: cover the area in drool (the dog is spitting)

panel 5: refer to step 3 (the dog, head in the air, continues barking)

panel 6: ensure the people understand the urgency of the situation, then repeat step 3. (the dog is stomping, and huffing, looking toward the reader)

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womensartbluesky.bsky.social @womensartbluesky.bsky.social · May 25

Alexandra Buckle, contemporary printmaker known for her woodland scenes created via linocuts #WomensArt

Print featuring a lush green woodland scene with dappled bright sunlight and reflections on a stream to the right

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Brian Grubb @briancgrubb.bsky.social · May 14

not sure how i can be expected to focus on anything else today now that i've seen the promo photo from the Madden movie with Christian Bale as Al Davis and Nicolas Cage as John Madden

promo photo from the upcoming Madden movie with Christian Bale as Al Davis and Nicolas Cage as John Madden

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Alex Naka @gottapatchemall.bsky.social · May 2

Snake venom protection by a cocktail of varespladib and broadly neutralizing human antibodies
www.cell.com/cell/fulltex...

broad spectrum antivenom

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Alex Naka @gottapatchemall.bsky.social · May 1

ATLAS: a rationally designed anterograde transsynaptic tracer
www.nature.com/articles/s41...

very cool

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