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

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

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...

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

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!

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:

First clouds over Stanford since spring

I think having an arbitrary threshold for statistical significance does more harm than good. It creates artificially black or white conclusions (there was a significant difference or not, with the word significant often omittted leading to bad misunderstandings) when knowledge is actually all gray.

“A legitimate PhD-level expert in anything,” they said. “Show me a diagram of the US presidents since FDR, with their names and years in office under their photos,” I said.

And now the 3rd paper this week using ASAP-family voltage indicators in mice to look at fast neuronal activity. In this case, collaborators Jiannis Taxidis and Peyman Golshani used ASAP3 to record spiking in PV and SST interneurons in the hippocampus. Published yesterday in @natneuro.nature.com

A negative side-effect of technological abundance is that it does not train people to deal with resource-limited conditions. Growing up with the easy ability to produce productivity outputs, people lose appreciation for, and ability to identify, creative and economically resourceful solutions.

Two voltage imaging studies in two days using ASAP fluorescent indicators. First, visualizing electrical brain waves with ASAP3, in Cell. Free link below. Though recorded by EEG for 100 years, how brain waves arise from different neuron types has been unclear. authors.elsevier.com/sd/article/S...

New powerful article up in the New York Times on cancelled and delayed grants www.nytimes.com/interactive/...

Received a 2% (top 2%) score on a NIH R21 grant last fall, and it won't get funded. This decision was made before the new administration, actually, showing that NIH has not lived up to its mission to fund the best science for a while. It's only going to get worse now with the budget cuts.

We had a tremendous conversation about these NIH cuts at @americanprogress.bsky.social with @hardeepsinghmd.bsky.social + @michaelzlin.bsky.social + @cdmenefee.bsky.social + @thehowie.bsky.social that was as timely in early April as it is today www.americanprogress.org/events/resea...

Academia has turned into industry, in that grants and papers are awarded based on measurable productivity metrics. The use of each dollar granted is increasingly scrutinized and costs are driven down through competition. Being an academic feels like running a mom-and-pop CRO sometimes.

If you're interested in optical reporting of neuronal activity, and can get to Venice, there are a couple of spots left at the Neuroscience School of Advanced Studies in Neurophotonics, 5/31 to 6/7. www.neurosas.org/advanced-cou...

It's Star Wars day, so what am I doing? Submitting two papers, of course

Our new paper is out in Science. What is the synaptic plasticity rule in the brain, we asked. It turns out there are multiple, even within individual neurons. Congrats Jake! www.science.org/doi/10.1126/...

A very thoughtful Perspective on our recent paper by Ayelén Groisman and Johannes Letzkus. Thank you! www.science.org/doi/10.1126/...

Carl Sagan was prescient.

Alan Garber for President (or any other person with a good heart and good brains willing to stand up for the rule of law... you know, traditional American qualities)

Where do things stand with the Abrego Garcia case, and where will they go from here? Via "One First," I look at the ridiculousness of the government's position and behavior; the options available to Judge Xinis; and the case's (mounting) broader ramifications: www.stevevladeck.com/p/143-the-st...

It's vastly underreported that the person driving the worst aspects of Trump's agenda is Stephen Miller. Bannon saw Trump as a vessel for his agenda but is now sidelined. Musk came on late and isn't 24/7 in the WH. Stephen Miller has been with Trump the whole time and has fed him every bad idea.

Measles likely came from cows (via rinderpest) around the 6th century BCE. For 2,500 years, we didn’t evolve superhuman resistance—children just died. Real protection only came in the 1960s, with vaccines. Our superpower isn’t evolving into superhumans. It’s outthinking pathogens.

Congrats to my friend David Liu, inventor of base editing, prime editing, and many other genome and molecular engineering methods, for a well deserved Breakthrough Prize David demonstrates how much positive impact comes from combining creativity with scientific insight (and some NIH funding).

77% of funds already appropriated by Congress for neuroscience research are not being spent. Meanwhile Alzheimer's and Parkinson's are not going to cure themselves. www.thetransmitter.org/funding/newl...

Our study on the molecular basis of shifts in receptor recognition by western equine encephalitis virus (WEEV) in the past century, led by Xiaoyi Fan and @wanyuviridae.bsky.social , is online! 👏🎉 www.cell.com/cell/fulltex...

AI was going to transform the world economy. Yesterday it did—not by doing anything useful, but when imbeciles used to it set tariff raters. AI was going to transforming education. Today it has— not by creating better learning platforms but instead by undermining ones have worked for centuries. 🧵

This article does a great job describing the lives of young American scientists: “You roll up your sleeves, try to make or discover something useful and then let the scientific community try to punch holes in your work to make sure that it’s sound”

Despite daily disruptions, scientists try to use logic and creativity to help fellow humans. Thus I would like to report our latest work describing microbial-independent deep assembly and screening, a method that goes from primers to mammalian cell assays in 1 day. www.biorxiv.org/content/10.1...

New hope for families battling Dravet Syndrome. Scientists have developed a new gene replacement therapy that could improve treatments for a rare and life-altering form of epilepsy. 🧵 #Neuroskyence #DravetSyndrome

There are days in life that shake you. I’m shattered 💔 to share that I just found out that the US Government terminated my 2024 NIH Director’s Early Independence Award (~$2 million), threatening my long-promised assistant professor job at Columbia University & academic career... 1/🧵

Helping my sister spread the word about a one-of-a-kind experiential trip to Japan with hot springs, a beer factory, and temple and home stays. Date: 2025 October 13-27 More information at www.sunnyvalesistercity.org/programs_AEP.html

Check out our latest Hot Plasmids post, featuring cool new tools like self-labeling constructs from @dozenoaks.bsky.social, an improved voltage sensor from @michaelzlin.bsky.social, prime editing in dicot plants, and more! blog.addgene.org/hot...

Getting worse

Here’s the secret on Trump and tariffs: he gets to look tough by threatening them but he’s scared to death to use them or honestly, to actually do anything. This is why he only picks on our friends because he looks tough but isn’t. Also:

I guess it's too much to expect reviewers to actually read your proposal before coming up with complaints about it.

🧪 Working to develop #drugs to treat #chikungunya ? Check out new fluorogenic substrates that help read out viral protease activity, developed by @tulsiupadhyay.bsky.social @westberglab.com @eunayoo.bsky.social @michaelzlin.bsky.social et al! pubmed.ncbi.nlm.nih.gov/39981948/

I joined @pbsnews.org tonight to talk about Elon Musk ‘accidentally cancelling’ Ebola prevention And what must do to prepare for and respond to outbreaks all over the world It’s not just the right thing to do, but it keeps us all safer as well Watch ⬇️ youtu.be/4ZzNkcZe5v4

Had an awesome visit to @stowersinstitute.bsky.social in Kansas City. Great to see the amazing research going on there on fundamental questions of how organisms adapt and thrive, in a variety of models from corals to mice.

Looks like a new hemorrhagic virus from bats in Congo is spreading between people. In Jan, 3 children ate a bat and died. Total deaths now 53 out of 431 reported cases. Symptoms were fever, vomiting, diarrhea, nosebleeds, and vomiting of blood. Not Ebola or Marburg. www.nytimes.com/2025/02/25/w...

It's amazing that there are some people who think AI is going to create better drugs on its own when Google Maps can't even identify the shortest route correctly despite tons of real time data.

NIH memo issued yesterday restarts award issuance, confirms they should have restarted after the 1/31 court ruling popular.info/p/breaking-n...

Stunned by attacks on the scientific research system, early career scientists plan a D.C. demonstration and a national ‘Stand Up for Science’ event.

Troubling Second top NIH official, who oversaw awarding of research grants, departs abruptly www.statnews.com/2025/02/13/n... via @statnews.com

Happy to announce our latest study in @nchembio.bsky.social, "Pharmacodynamics of Akt drugs revealed by a kinase-modulated bioluminescent indicator" Drug candidates are routinely evaluated for endurance in blood (pharmacokinetics/PK) But what is actually important is pharmacodynamics (PD)

What's happening in America is that, in the most literal sense, internet trolls have taken over the government.

If you don't reform compromised systems like adults, it seems that eventually armed children will show up and reform things for you.

So Trump-Musk propose to save $7B each year at the cost of making biomedical research a money-losing activity for universities and research institutes. Expect no new hires of biomedical researchers and, in a few years, no new discoveries. Talk about killing the golden goose.