Excited to introduce ScaRCaMP — a highly blue-light resistant red GECI. 🔴
Now live on bioRxiv and marking my first PhD preprint (2nd for the Marko lab).
Would love feedback from the community!!
We never got the press coverage of the drop in FY2024 because by the time it was known there were bigger stories to cover. But we went from a declining situation (at least when it comes to time-efficiency of grant-writing) to a disaster.
Note there was already a drop in FY2024 which ended 9/2024 under Biden
Don't know why exactly but it's consistent with anecdotal experience of tightening paylines even before the election, and the ever-decreasing appetite for risk and need for abundant "preliminary data" (more like definitive data)
That's per applicant, not application, and only for R01s or equivalent. Per-app rates were below 8% in most institutes, so the average applicant applied ~2x
The % drop was fairly uniform by career stage:
New 10.0% = 44% less
At Risk 16.9% = 37% less
Established 19.6% = 40% less
ESI 18.9% = 37% less
NIH funding rate per applicant dropped 38% in FY2025 vs 2022, from 27.1% to 16.7%
Here's a breakdown by career stage. Why FY2022 vs FY2025?
• FY2022 was first FY with budget passed and administered by Biden
• FY2025 budget was in CR until 3/15/2025, so budget and most grants were under the Trump WH
Roger's passing 10y ago was a loss not just for science but for society at large. Some of what plagues some fields today (the constant overselling and jockeying for attention) would likely be curtailed with just a few frank comments from him.
Roger, you are very much missed.
What fewer people knew about, however, was Roger's kindness and integrity. He never claimed more than he deserved, letting the science speak for itself, and giving credit wherever due. He'd give an honest opinion when asked, whether positive or negative, something I really valued.
Roger's contribution to GFP wasn't its discovery or its first demonstration outside jellyfish, but in understanding its chemistry, and then using that to engineer BFP, CFP, YFP, and a series of indicators, including the first FRET and single-FP calcium indicators.
Roger arguably deserved his own Nobel Prize earlier, for the invention of fluorescent calcium dyes such as Fura-2 (beginning as PhD student self-taught in organic synthesis), which are widely used as indicators of neuronal firing, myocyte contraction, and GPCR activation.
Roger was an interdisciplinary chemical biologist long before those terms existed. His BA was in chemistry & physics, and his PhD in physiology. He combined the deepest understanding of chemistry (since high school, below) with curiosity for the hardest biological questions.
Today I'd like to honor the memory of my mentor and friend, Roger Tsien, born 1952 February 1. Today would have been Roger's 74th birthday.
Most know Roger for his 2008 Chemistry Nobel Prize with Shimomura and Chalfie. Roger made GFP into the versatile imaging method it is now.
In some countries the outbreak of bloodshed inspires the opposition party to call for the leader to resign
For #fluorescentfriday, an image contributed by my daughter showing GFP in a vial.
Specifically mClover3, of course.
Mamdani has only been Mayor for a day & criminals are already fleeing New York
Somehow managed to survive crossing these streets until I was 5 years old.
Look closely and you'll see the Buddha of Baguashan. Would walk up to it nearly every day, along a stream where housewives did their laundry.
Back in my birthplace, Taiwan. Within 2 generations it went from agrarian and poor to creating the 2-nm technology that drives the world economy. My grandparents grew up as farmers, my parents still save every last grain of rice. Step out of Taipei and you realize the old Taiwan is still there.
Immunity debt's "...explanatory power has faded as the number of non-covid infections has kept rising each year...
A growing number of scientists believe that the SARS-CoV-2 virus may instead be subtly altering our immune systems." 🛟😷medsky
Thanks too to @spencerlaveresmith.bsky.social, @michaelgoard.bsky.social, @andyalexander.bsky.social, Sung-Soo Kim, Mathieu Louis, and MCDB students for thought-provoking discussions. It's inspiring to see so many people advancing the frontiers of neuroscience with sharp ideas and smart execution.
Had a really nice visit to UCSB, learning about the awesome neuroscience research there and presenting our work on voltage imaging in the molecular cellular and developmental biology seminar series.
Thanks to my host Ikuko Smith, who might have the best office view in all of UC!
That's exactly right, but if you want ms temporal resolution, well then you have to image at near kHz speeds
Which then means the quality of the optics and camera are more important now.
Oh not your review, which was really great (and thanks for citing us).
True at slower speeds GECIs have higher SNRs. The problem becomes when people assume SNR differences in the cell are proportional to molecular performance. It may be okay within a design (eg GCaMP3 vs 6) but not between designs.
It depends on how much you are willing to overexpress the GCaMP. Brinks and Cohen estimated the abundance difference as 100x. We find we can overexpress GCaMP to get 100x more per cell body, but then get into the realm of lower dF/F.
www.sciencedirect.com/science/arti...
In fact, I should point out that we recently worked with Promega to improve bioluminescent imaging in the brain further. We identified cephalofurimazine-9 (CFz9), a modification of the original CFz, as a substrate with higher sustainable brightness in the brain.
www.nature.com/articles/s41...
Our hope is to speed up biological and therapeutic discovery for all researchers by visualizing a wide variety of cells, pathogens, pathways etc, all noninvasively and using simple inexpensive equipment. So far the results are looking good!
The visit (at Promega that is) was especially illuminating and motivating. It was great to learn that the in vivo NanoLuc substrates we identified together with the Promega chemists are really catching on in the biomedical research community, especially for tumor and immune cell detection.
Had the pleasure of visiting @promegacorporation.bsky.social's chemistry group in beautiful San Luis Obispo. Thanks to Wenhui Zhou and the other amazing chemists for hosting me!
Didn't get a photo at Promega itself but here's one from our vineyard visit afterwards. Just a typical SLO evening.
It's like saying fewer people have worked on engineering airplanes than cars, so there are fewer pilots than drivers — each part might be true, but the former didn't cause the latter. Rather it's an inherently harder problem where both engineering and usage require specialized and expensive methods.
In sum, the belief that GEVIs haven't been engineered as much as GECIs and thus voltage imaging is less commonly performed than calcium imaging links two true statements as cause-effect when they are more related as effect-effect: both are effects of the difficulty of working with voltage.
Eventually this will get cleared up, maybe after we get a chance to present our comparisons between GECIs and GEVIs at different rates. For now though just a reminder that simple explanations are not always 100% correct.
