James Fraser
@fraserlab.com
Professor and Chair @UCSF/@UCSF_BTS - dynamic structural biology and open science - (he/him) - fraserlab.com
it's not my style - but it does have a place for those in less protected positions. Luckily @prereview.bsky.social has a great mechanism for this!
See the persistent pseudonyme option:
See the persistent pseudonyme option:
September 12, 2025 at 5:31 PM
it's not my style - but it does have a place for those in less protected positions. Luckily @prereview.bsky.social has a great mechanism for this!
See the persistent pseudonyme option:
See the persistent pseudonyme option:
Can’t square that with:
September 9, 2025 at 2:34 PM
Can’t square that with:
My view: posting a preprint is already an explicit invitation for community feedback. Authors shouldn’t have to opt in - especially to hear when ORCID-authenticated reviews are posted on some of their trusted partners that they include on their reviews and context side bar
September 8, 2025 at 3:59 PM
My view: posting a preprint is already an explicit invitation for community feedback. Authors shouldn’t have to opt in - especially to hear when ORCID-authenticated reviews are posted on some of their trusted partners that they include on their reviews and context side bar
These results suggest that stabilizing Orf9b’s (lipid-bound) dimeric state could be a future therapeutic target. Disrupting lipid interactions might bias Orf9b towards a form that can’t bind Tom70, restoring immune activation.
February 18, 2025 at 10:22 PM
These results suggest that stabilizing Orf9b’s (lipid-bound) dimeric state could be a future therapeutic target. Disrupting lipid interactions might bias Orf9b towards a form that can’t bind Tom70, restoring immune activation.
CJ measured key rate constants that constrained a model to show how lipid binding shifts Orf9b’s equilibrium towards the homodimer, preventing Tom70 interaction. The lipid-free form comes to equilibrium in seconds, whereas the lipid-bound form takes hours-days!
February 18, 2025 at 10:22 PM
CJ measured key rate constants that constrained a model to show how lipid binding shifts Orf9b’s equilibrium towards the homodimer, preventing Tom70 interaction. The lipid-free form comes to equilibrium in seconds, whereas the lipid-bound form takes hours-days!
Here, we developed a quantitative biophysical model to describe the coupled equilibria of Orf9b dimerization and Tom70 binding, revealing how lipid binding tunes the system.
![ODE for Tom70/Orf9b interactions:
1. d[Orf9b-FITC]/dt = -k1[Orf9b-FITC][Tom70]+k2[Orf9b-FITC:Tom70]
2. d[Orf9b β-monomer]/dt = 2(-k3[Orf9b β-monomer]^2+k4[Orf9b dimer])-kα[Orf9b β-
monomer]^2+kβ[Orf9b α-monomer]
3. d[Orf9b dimer]/dt = k3[Orf9b β-monomer]^2-k4[Orf9b dimer]
4. d[Tom70]/dt = -k1[Orf9b-FITC][Tom70]-k5[Orf9b α-monomer][T]+k6[Orf9b α-
monomer:Tom70]+k2[PT]
5. d[Orf9b α-monomer:Tom70]/dt = k5[Orf9b α-monomer][Tom70]-k6[Orf9b α-
monomer:Tom70]
6. d[Orf9b α-monomer]/dt = -k5[Orf9b α monomer][Tom70]-kβ[Orf9b α-monomer]+k6[Orf9b
α-monomer:Tom70]+kα[Orf9b β-monomer]^2](https://cdn.bsky.app/img/feed_thumbnail/plain/did:plc:72iipghcsu54juasln5jswpx/bafkreiapucgptz5f327xiworglyp5uopftoztgjqwnp6lxrm3dzikb2eyu@jpeg)
February 18, 2025 at 10:22 PM
Here, we developed a quantitative biophysical model to describe the coupled equilibria of Orf9b dimerization and Tom70 binding, revealing how lipid binding tunes the system.
We show that Orf9b exists in a dynamic equilibrium between a homodimeric and monomeric state. The monomer binds to the mitochondrial protein Tom70, suppressing immune responses. Lipid binding to Orf9b stabilizes the homodimer, acting as a switch to slow down Tom70 engagement.
February 18, 2025 at 10:22 PM
We show that Orf9b exists in a dynamic equilibrium between a homodimeric and monomeric state. The monomer binds to the mitochondrial protein Tom70, suppressing immune responses. Lipid binding to Orf9b stabilizes the homodimer, acting as a switch to slow down Tom70 engagement.
New acknowledgement of @elife.bsky.social lack of Impact Factor in proofs... see response!
February 5, 2025 at 6:54 PM
New acknowledgement of @elife.bsky.social lack of Impact Factor in proofs... see response!
Continuing the ☘️🍪▶️📄. Yesterday I was EXTREMELY disappointed to only receive 6 preprints (🧵) for 18 Caramel deLites.
We have "preprint hating cookie thieves" (great name for a rock band!) on the 4th floor!
I'm trying again - this time with the innovation of Scotch tape attached to the cookie box!
We have "preprint hating cookie thieves" (great name for a rock band!) on the 4th floor!
I'm trying again - this time with the innovation of Scotch tape attached to the cookie box!
February 4, 2025 at 4:24 PM
Continuing the ☘️🍪▶️📄. Yesterday I was EXTREMELY disappointed to only receive 6 preprints (🧵) for 18 Caramel deLites.
We have "preprint hating cookie thieves" (great name for a rock band!) on the 4th floor!
I'm trying again - this time with the innovation of Scotch tape attached to the cookie box!
We have "preprint hating cookie thieves" (great name for a rock band!) on the 4th floor!
I'm trying again - this time with the innovation of Scotch tape attached to the cookie box!
Streptogramins are promising antibiotics for treating resistant bacterial infections, but their efficacy is threatened by Vat enzymes, which inactivate streptogramins by acetylation (blocking a key interaction with the ribosome). So we set out to block the blocker!
February 3, 2025 at 4:58 PM
Streptogramins are promising antibiotics for treating resistant bacterial infections, but their efficacy is threatened by Vat enzymes, which inactivate streptogramins by acetylation (blocking a key interaction with the ribosome). So we set out to block the blocker!
Our latest work on tackling streptogramin resistance in collaboration with the Seiple lab is now up as a preprint. We (led by Pooja Asthana) targeted a resistance enzyme, VatD, with fragment-based drug discovery!
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
February 3, 2025 at 4:58 PM
Our latest work on tackling streptogramin resistance in collaboration with the Seiple lab is now up as a preprint. We (led by Pooja Asthana) targeted a resistance enzyme, VatD, with fragment-based drug discovery!
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
New strategy for discovering preprints.
Cookies to Offline RSS feed!
🍪🍀
Cookies to Offline RSS feed!
🍪🍀
February 3, 2025 at 4:23 PM
New strategy for discovering preprints.
Cookies to Offline RSS feed!
🍪🍀
Cookies to Offline RSS feed!
🍪🍀
Next, we took inspiration from more polar fragments binding lower in the original binding site and designed KABLE (Kemp eliminase ALBE). With a few additional mutations from a single round of screening it has a catalytic efficiency (600,000 M⁻¹s⁻¹) on par with the natural enzymes.
January 31, 2025 at 6:20 PM
Next, we took inspiration from more polar fragments binding lower in the original binding site and designed KABLE (Kemp eliminase ALBE). With a few additional mutations from a single round of screening it has a catalytic efficiency (600,000 M⁻¹s⁻¹) on par with the natural enzymes.
Yuda Chen noticed that some of the fragments resembled coumarins. So they redesigned the binding site and created FABLE (Fluorescent ABLE) —a protein that binds turn-on fluorophores.
ABLE->FABLE generalist to a specialist sensor with 100-fold turn-on fluorescence enhancement!
ABLE->FABLE generalist to a specialist sensor with 100-fold turn-on fluorescence enhancement!
January 31, 2025 at 6:20 PM
Yuda Chen noticed that some of the fragments resembled coumarins. So they redesigned the binding site and created FABLE (Fluorescent ABLE) —a protein that binds turn-on fluorophores.
ABLE->FABLE generalist to a specialist sensor with 100-fold turn-on fluorescence enhancement!
ABLE->FABLE generalist to a specialist sensor with 100-fold turn-on fluorescence enhancement!
Lena Bergmann and Galen Correy used X-ray crystallography as a binding assay.
ABLE turned out to be a generalist, binding 43 fragments in two distinct conformations.
(side note, Nick and Justin Biel started this as COVID hit... but it paused until Lena picked it back up!)
ABLE turned out to be a generalist, binding 43 fragments in two distinct conformations.
(side note, Nick and Justin Biel started this as COVID hit... but it paused until Lena picked it back up!)
January 31, 2025 at 6:20 PM
Lena Bergmann and Galen Correy used X-ray crystallography as a binding assay.
ABLE turned out to be a generalist, binding 43 fragments in two distinct conformations.
(side note, Nick and Justin Biel started this as COVID hit... but it paused until Lena picked it back up!)
ABLE turned out to be a generalist, binding 43 fragments in two distinct conformations.
(side note, Nick and Justin Biel started this as COVID hit... but it paused until Lena picked it back up!)
Thrilled to take a break from doom and gloom to share our latest work collaborating with the DeGrado lab! We took a de novo designed protein, screened it for ligand binding using X-rays, and used the hits to evolve two wildly different functions: fluorescent turn-on and Kemp elimination catalysis. 🧵
January 31, 2025 at 6:20 PM
Thrilled to take a break from doom and gloom to share our latest work collaborating with the DeGrado lab! We took a de novo designed protein, screened it for ligand binding using X-rays, and used the hits to evolve two wildly different functions: fluorescent turn-on and Kemp elimination catalysis. 🧵
I've had such a lucky life in science. From time to time my mind drifts and I think about my two greatest mentors passing away too young. It stops me cold in my tracks. I've been staring at this picture for 15 minutes...
January 23, 2025 at 6:38 PM
I've had such a lucky life in science. From time to time my mind drifts and I think about my two greatest mentors passing away too young. It stops me cold in my tracks. I've been staring at this picture for 15 minutes...
Treating myself to a visit to the synchrotron for Thanksgiving with Galen and Julius - Photons on! 💎💫
November 26, 2024 at 6:48 PM
Treating myself to a visit to the synchrotron for Thanksgiving with Galen and Julius - Photons on! 💎💫
I recall this used to be a problem for Science too - but they have a good solution (figure legend on right, scrollable!) @richardsever.bsky.social
November 18, 2024 at 6:18 PM
I recall this used to be a problem for Science too - but they have a good solution (figure legend on right, scrollable!) @richardsever.bsky.social
Haven't complained about this in a while, but now that @biorxivpreprint.bsky.social has such a great full text view for web... I HATE how clicking on the image brings up a magnified image that gets covered dynamically with the figure legend when you mouse over it... SO ANNOYING!!!!
November 18, 2024 at 6:14 PM
Haven't complained about this in a while, but now that @biorxivpreprint.bsky.social has such a great full text view for web... I HATE how clicking on the image brings up a magnified image that gets covered dynamically with the figure legend when you mouse over it... SO ANNOYING!!!!
Just added the @bsky.app logo and links to our lab website members page (fraserlab.com/members) - these types of links are a great feature (along with the timeline, cartoon, and easter 🥚 pictures)... thanks to @tomo.science for providing the foundation - (to copy: fraserlab.com/2020/05/03/C...)
November 16, 2024 at 11:34 PM
Just added the @bsky.app logo and links to our lab website members page (fraserlab.com/members) - these types of links are a great feature (along with the timeline, cartoon, and easter 🥚 pictures)... thanks to @tomo.science for providing the foundation - (to copy: fraserlab.com/2020/05/03/C...)
Great drinks with Gira and Damian too!!!
November 13, 2024 at 4:11 PM
Great drinks with Gira and Damian too!!!
Lab Halloween Costumes - (imagine the minus sign)...
November 1, 2023 at 12:27 AM
Lab Halloween Costumes - (imagine the minus sign)...
I see this all the time - you don't need to wait for a journal to ask you to review - JUST REVIEW THE PREPRINT and post your review!
We do it all the time: fraserlab.com/reviews
The majority of the time, a journal asks us to include the review in their process AFTER we post!
We do it all the time: fraserlab.com/reviews
The majority of the time, a journal asks us to include the review in their process AFTER we post!
October 4, 2023 at 3:22 PM
I see this all the time - you don't need to wait for a journal to ask you to review - JUST REVIEW THE PREPRINT and post your review!
We do it all the time: fraserlab.com/reviews
The majority of the time, a journal asks us to include the review in their process AFTER we post!
We do it all the time: fraserlab.com/reviews
The majority of the time, a journal asks us to include the review in their process AFTER we post!