Jason Yu
@jasonyjc.bsky.social
PhD Student at U of T Biochemistry 🇨🇦 | Rubinstein Lab | Cryo-EM | Mycobacteria
https://scholar.google.com/citations?hl=en&user=PRTcXNsAAAAJ
https://scholar.google.com/citations?hl=en&user=PRTcXNsAAAAJ
Reposted by Jason Yu
Mycobacterium tuberculosis is an outlier in many ways. One of them is keeping a high degree of functional redundancy despite its obligate pathogen lifestyle. In this review, we reflect on the biological meaning of M. tuberculosis functional redundancies.
journals.plos.org/plospathogen...
journals.plos.org/plospathogen...
Essential redundancies fuel Mycobacterium tuberculosis adaptation to the host
Redundancy in biology is, at a glance, counterintuitive because if the function of two gene products completely overlaps then, throughout the course of evolution, one of the genes will likely accumula...
journals.plos.org
December 7, 2025 at 12:07 PM
Mycobacterium tuberculosis is an outlier in many ways. One of them is keeping a high degree of functional redundancy despite its obligate pathogen lifestyle. In this review, we reflect on the biological meaning of M. tuberculosis functional redundancies.
journals.plos.org/plospathogen...
journals.plos.org/plospathogen...
Reposted by Jason Yu
Does this create an Achilles’ heel, and can you drug it? Turns out: yes.
Congrats to Barbara, Vanisha, Liz, and the rest of the team.
www.nature.com/articles/s41...
Congrats to Barbara, Vanisha, Liz, and the rest of the team.
www.nature.com/articles/s41...
Transcription co-inhibition alters drug resistance evolution and enhances Mycobacterium tuberculosis clearance from granulomas - Nature Microbiology
Targeting two distinct steps of the transcription process yields synergistic antibiotics that kill non-replicating Mycobacterium tuberculosis and reduce drug resistance.
www.nature.com
December 3, 2025 at 11:10 AM
Does this create an Achilles’ heel, and can you drug it? Turns out: yes.
Congrats to Barbara, Vanisha, Liz, and the rest of the team.
www.nature.com/articles/s41...
Congrats to Barbara, Vanisha, Liz, and the rest of the team.
www.nature.com/articles/s41...
Reposted by Jason Yu
Exciting collab with Paul Palme, Peter Imming, & Adrian Richter!
Guided by @courbongautier.bsky.social's structure of myco ATP synthase bound to a squaramide, they have made SQAs that are less toxic, more potent, more stable than AstraZeneca's SQ31f
#MedChem #TB #NTM
pubs.acs.org/doi/full/10....
Guided by @courbongautier.bsky.social's structure of myco ATP synthase bound to a squaramide, they have made SQAs that are less toxic, more potent, more stable than AstraZeneca's SQ31f
#MedChem #TB #NTM
pubs.acs.org/doi/full/10....
Design, Synthesis, and Biological Evaluation of Mono- and Diamino-Substituted Squaramide Derivatives as Potent Inhibitors of Mycobacterial Adenosine Triphosphate (ATP) Synthase
Amides of squaric acid are new drug candidates with activity against mycobacteria. Like the approved drug bedaquiline, these compounds achieve efficacy by inhibiting mycobacterial ATP synthase. Howeve...
pubs.acs.org
November 27, 2025 at 11:53 PM
Exciting collab with Paul Palme, Peter Imming, & Adrian Richter!
Guided by @courbongautier.bsky.social's structure of myco ATP synthase bound to a squaramide, they have made SQAs that are less toxic, more potent, more stable than AstraZeneca's SQ31f
#MedChem #TB #NTM
pubs.acs.org/doi/full/10....
Guided by @courbongautier.bsky.social's structure of myco ATP synthase bound to a squaramide, they have made SQAs that are less toxic, more potent, more stable than AstraZeneca's SQ31f
#MedChem #TB #NTM
pubs.acs.org/doi/full/10....
Reposted by Jason Yu
🚀 Hiring: Cryo-EM Application Scientist, Marketing!
Develop and deliver high-impact scientific marketing content, illustrate the value of new #CryoSPARC features and #cryoEM advances, and help scientists understand how our tools can help solve their problems.
structura.bio/careers/appl...
Develop and deliver high-impact scientific marketing content, illustrate the value of new #CryoSPARC features and #cryoEM advances, and help scientists understand how our tools can help solve their problems.
structura.bio/careers/appl...
Structura Bio | Structura Bio
structura.bio
November 20, 2025 at 9:00 PM
🚀 Hiring: Cryo-EM Application Scientist, Marketing!
Develop and deliver high-impact scientific marketing content, illustrate the value of new #CryoSPARC features and #cryoEM advances, and help scientists understand how our tools can help solve their problems.
structura.bio/careers/appl...
Develop and deliver high-impact scientific marketing content, illustrate the value of new #CryoSPARC features and #cryoEM advances, and help scientists understand how our tools can help solve their problems.
structura.bio/careers/appl...
Reposted by Jason Yu
#NewResearch
A bile acid-bound structure of toxin TcdB revealed the mechanism of inhibition and guided the design of a synthetic bile acid that alleviated C. difficile infection in mice.
#MicroSky 🦠💊
www.nature.com/articles/s41...
A bile acid-bound structure of toxin TcdB revealed the mechanism of inhibition and guided the design of a synthetic bile acid that alleviated C. difficile infection in mice.
#MicroSky 🦠💊
www.nature.com/articles/s41...
Structure-guided design of a synthetic bile acid that inhibits Clostridioides difficile TcdB toxin - Nature Microbiology
A bile acid-bound structure of toxin TcdB revealed the mechanism of inhibition and guided the design of a synthetic bile acid that alleviated Clostridioides difficile infection in mice.
www.nature.com
November 18, 2025 at 2:07 PM
#NewResearch
A bile acid-bound structure of toxin TcdB revealed the mechanism of inhibition and guided the design of a synthetic bile acid that alleviated C. difficile infection in mice.
#MicroSky 🦠💊
www.nature.com/articles/s41...
A bile acid-bound structure of toxin TcdB revealed the mechanism of inhibition and guided the design of a synthetic bile acid that alleviated C. difficile infection in mice.
#MicroSky 🦠💊
www.nature.com/articles/s41...
Reposted by Jason Yu
With the Wilmanns lab @embl.org we reveal cryoEM structures of an essential, bifunctional acyl-CoA carboxylase from mycobacteria. @wertheimufscripps.bsky.social
This ~ 600 kDa enzyme is asymmetric, rotatory, has unusual stoichiometry, and unique E5 subunits.
www.biorxiv.org/content/10.1...
This ~ 600 kDa enzyme is asymmetric, rotatory, has unusual stoichiometry, and unique E5 subunits.
www.biorxiv.org/content/10.1...
www.biorxiv.org
November 17, 2025 at 1:38 PM
With the Wilmanns lab @embl.org we reveal cryoEM structures of an essential, bifunctional acyl-CoA carboxylase from mycobacteria. @wertheimufscripps.bsky.social
This ~ 600 kDa enzyme is asymmetric, rotatory, has unusual stoichiometry, and unique E5 subunits.
www.biorxiv.org/content/10.1...
This ~ 600 kDa enzyme is asymmetric, rotatory, has unusual stoichiometry, and unique E5 subunits.
www.biorxiv.org/content/10.1...
Reposted by Jason Yu
Our November issue is available at journals.iucr.org/d/issues/202...
On the cover: recent studies demonstrate that the range of samples suitable for cryo-EM single-particle analysis is expanding towards increasingly more native samples. Read the review at shorturl.at/mitjg
On the cover: recent studies demonstrate that the range of samples suitable for cryo-EM single-particle analysis is expanding towards increasingly more native samples. Read the review at shorturl.at/mitjg
November 5, 2025 at 1:29 PM
Our November issue is available at journals.iucr.org/d/issues/202...
On the cover: recent studies demonstrate that the range of samples suitable for cryo-EM single-particle analysis is expanding towards increasingly more native samples. Read the review at shorturl.at/mitjg
On the cover: recent studies demonstrate that the range of samples suitable for cryo-EM single-particle analysis is expanding towards increasingly more native samples. Read the review at shorturl.at/mitjg
Reposted by Jason Yu
On a gruelling hunt for rare associated molecules in your #cryoEM particle stack and not sure where to look?
Discover practical tips and tricks in our new case study using #CryoSPARC v4.7.1 where we find and refine a low-population interaction partner!
guide.cryosparc.com/processing-d...
Discover practical tips and tricks in our new case study using #CryoSPARC v4.7.1 where we find and refine a low-population interaction partner!
guide.cryosparc.com/processing-d...
October 30, 2025 at 1:33 PM
On a gruelling hunt for rare associated molecules in your #cryoEM particle stack and not sure where to look?
Discover practical tips and tricks in our new case study using #CryoSPARC v4.7.1 where we find and refine a low-population interaction partner!
guide.cryosparc.com/processing-d...
Discover practical tips and tricks in our new case study using #CryoSPARC v4.7.1 where we find and refine a low-population interaction partner!
guide.cryosparc.com/processing-d...
Reposted by Jason Yu
New lab preprint!
@zestytoast.bsky.social tagged a scarce mycobacterial protein in M. smegmatis with TwinStep but got… something? @kjamali.bsky.social's ModelAngelo built models & @martinsteinegger.bsky.social's FoldSeek IDed them as the biotin-containing MCC & LCC complexes
🧵
tinyurl.com/ukny4ptz
@zestytoast.bsky.social tagged a scarce mycobacterial protein in M. smegmatis with TwinStep but got… something? @kjamali.bsky.social's ModelAngelo built models & @martinsteinegger.bsky.social's FoldSeek IDed them as the biotin-containing MCC & LCC complexes
🧵
tinyurl.com/ukny4ptz
October 30, 2025 at 3:21 AM
New lab preprint!
@zestytoast.bsky.social tagged a scarce mycobacterial protein in M. smegmatis with TwinStep but got… something? @kjamali.bsky.social's ModelAngelo built models & @martinsteinegger.bsky.social's FoldSeek IDed them as the biotin-containing MCC & LCC complexes
🧵
tinyurl.com/ukny4ptz
@zestytoast.bsky.social tagged a scarce mycobacterial protein in M. smegmatis with TwinStep but got… something? @kjamali.bsky.social's ModelAngelo built models & @martinsteinegger.bsky.social's FoldSeek IDed them as the biotin-containing MCC & LCC complexes
🧵
tinyurl.com/ukny4ptz
Reposted by Jason Yu
Excited to release BoltzGen which brings SOTA folding performance to binder design! The best part of this project is collaborating with a broad network of leading wetlabs that test BoltzGen at an unprecedented scale, showing success on many novel targets and pushing the model to its limits!
October 26, 2025 at 10:40 PM
Excited to release BoltzGen which brings SOTA folding performance to binder design! The best part of this project is collaborating with a broad network of leading wetlabs that test BoltzGen at an unprecedented scale, showing success on many novel targets and pushing the model to its limits!
Reposted by Jason Yu
Learn how our hunt for the native structure of top antimalarial target PfATP4🧂led to the discovery of PfABP, an unknown essential binding partner, out now! @natcomms.nature.com 👉 rdcu.be/eLRlH 🦠🔬❄️
A team effort led by @mehsehret.bsky.social & Anurag Shukla @akhilvaidya.bsky.social! #cryoEM #malaria
A team effort led by @mehsehret.bsky.social & Anurag Shukla @akhilvaidya.bsky.social! #cryoEM #malaria
Endogenous structure of antimalarial target PfATP4 reveals an apicomplexan-specific P-type ATPase modulator
Nature Communications - Here, the authors present the 3.7 Å cryoEM structure of native sodium efflux pump PfATP4 from Plasmodium falciparum, revealing a bound protein that they term...
rdcu.be
October 20, 2025 at 12:55 PM
Learn how our hunt for the native structure of top antimalarial target PfATP4🧂led to the discovery of PfABP, an unknown essential binding partner, out now! @natcomms.nature.com 👉 rdcu.be/eLRlH 🦠🔬❄️
A team effort led by @mehsehret.bsky.social & Anurag Shukla @akhilvaidya.bsky.social! #cryoEM #malaria
A team effort led by @mehsehret.bsky.social & Anurag Shukla @akhilvaidya.bsky.social! #cryoEM #malaria
Reposted by Jason Yu
Check out our preprint! With new molecular mechanisms, 140 subtomogram averages, and ~600 annotated cells under different conditions, we @embl.org were able to describe bacterial populations with in-cell #cryoET. And there’s a surprise at the end 🕵️
www.biorxiv.org/content/10.1...
#teamtomo
www.biorxiv.org/content/10.1...
#teamtomo
October 15, 2025 at 6:26 AM
Check out our preprint! With new molecular mechanisms, 140 subtomogram averages, and ~600 annotated cells under different conditions, we @embl.org were able to describe bacterial populations with in-cell #cryoET. And there’s a surprise at the end 🕵️
www.biorxiv.org/content/10.1...
#teamtomo
www.biorxiv.org/content/10.1...
#teamtomo
Reposted by Jason Yu
Helical Reconstruction of Amyloids in cryoSPARC?
We present guidelines, limitations & future perspectives for processing amyloids in cryoSPARC @structurabio.bsky.social.
Great collaboration of the Kelly Lab and @landerlab.bsky.social #cryoEM #amyloid www.biorxiv.org/content/10.1...
We present guidelines, limitations & future perspectives for processing amyloids in cryoSPARC @structurabio.bsky.social.
Great collaboration of the Kelly Lab and @landerlab.bsky.social #cryoEM #amyloid www.biorxiv.org/content/10.1...
October 5, 2025 at 4:16 AM
Helical Reconstruction of Amyloids in cryoSPARC?
We present guidelines, limitations & future perspectives for processing amyloids in cryoSPARC @structurabio.bsky.social.
Great collaboration of the Kelly Lab and @landerlab.bsky.social #cryoEM #amyloid www.biorxiv.org/content/10.1...
We present guidelines, limitations & future perspectives for processing amyloids in cryoSPARC @structurabio.bsky.social.
Great collaboration of the Kelly Lab and @landerlab.bsky.social #cryoEM #amyloid www.biorxiv.org/content/10.1...
Reposted by Jason Yu
New week, new tool: Find our Protein Domain Designer tool to generate publication-ready protein domain diagrams here: domaindesigner.farnunglab.com
September 29, 2025 at 3:01 PM
New week, new tool: Find our Protein Domain Designer tool to generate publication-ready protein domain diagrams here: domaindesigner.farnunglab.com
Reposted by Jason Yu
I am thrilled to release ProteinDJ: a high-performance and modular protein design pipeline. Our open-source workflow incorporates #RFdiffusion, #ProteinMPNN, #FAMPNN, #AlphaFold2 and #Boltz-2. It is a fast, free, and fun way to design proteins (1/5)
doi.org/10.1101/2025.09.24.678028 #proteindesign
doi.org/10.1101/2025.09.24.678028 #proteindesign
September 28, 2025 at 9:16 PM
I am thrilled to release ProteinDJ: a high-performance and modular protein design pipeline. Our open-source workflow incorporates #RFdiffusion, #ProteinMPNN, #FAMPNN, #AlphaFold2 and #Boltz-2. It is a fast, free, and fun way to design proteins (1/5)
doi.org/10.1101/2025.09.24.678028 #proteindesign
doi.org/10.1101/2025.09.24.678028 #proteindesign
Reposted by Jason Yu
Finally in @nature.com 🎉
We uncovered step-wise mTORC1 activation on membrane: RAG–Ragulator recruits, RHEB pushes closer, and direct membrane contacts by RAPTOR + mTOR trigger full kinase activity.👉 The membrane is not just a platform — it’s part of the mechanism.
www.nature.com/articles/s41...
We uncovered step-wise mTORC1 activation on membrane: RAG–Ragulator recruits, RHEB pushes closer, and direct membrane contacts by RAPTOR + mTOR trigger full kinase activity.👉 The membrane is not just a platform — it’s part of the mechanism.
www.nature.com/articles/s41...
Structural basis for mTORC1 activation on the lysosomal membrane - Nature
Cryo-electron microscopy was used to study human mechanistic target of rapamycin complex 1 (mTORC1) activation on lysosomal membranes, showing progressive recruitment by RAG–Ragulator, RHEB and R...
www.nature.com
September 17, 2025 at 9:35 PM
Finally in @nature.com 🎉
We uncovered step-wise mTORC1 activation on membrane: RAG–Ragulator recruits, RHEB pushes closer, and direct membrane contacts by RAPTOR + mTOR trigger full kinase activity.👉 The membrane is not just a platform — it’s part of the mechanism.
www.nature.com/articles/s41...
We uncovered step-wise mTORC1 activation on membrane: RAG–Ragulator recruits, RHEB pushes closer, and direct membrane contacts by RAPTOR + mTOR trigger full kinase activity.👉 The membrane is not just a platform — it’s part of the mechanism.
www.nature.com/articles/s41...
Reposted by Jason Yu
We finally wrote up the paper for LocScale-2.0.
edu.nl/pvhxv
Please try it out. LocScale is evolving & we are actively building in new features and improvements. Your feedback will help us shape the next steps.
Code: cryotud.github.io/locscale/
Work by @alok-bharadwaj.bsky.social and Reinier.
edu.nl/pvhxv
Please try it out. LocScale is evolving & we are actively building in new features and improvements. Your feedback will help us shape the next steps.
Code: cryotud.github.io/locscale/
Work by @alok-bharadwaj.bsky.social and Reinier.
We are happy to release LocScale2.0: a tool for context-aware, confidence-weighted cryoEM map optimisation.
Taking two half maps as input, LcoScale-2.0 produces feature-enhanced maps along with a robust confidence score that guides objective map interpretation.
cryotud.github.io/locscale/
Taking two half maps as input, LcoScale-2.0 produces feature-enhanced maps along with a robust confidence score that guides objective map interpretation.
cryotud.github.io/locscale/
September 15, 2025 at 7:39 AM
We finally wrote up the paper for LocScale-2.0.
edu.nl/pvhxv
Please try it out. LocScale is evolving & we are actively building in new features and improvements. Your feedback will help us shape the next steps.
Code: cryotud.github.io/locscale/
Work by @alok-bharadwaj.bsky.social and Reinier.
edu.nl/pvhxv
Please try it out. LocScale is evolving & we are actively building in new features and improvements. Your feedback will help us shape the next steps.
Code: cryotud.github.io/locscale/
Work by @alok-bharadwaj.bsky.social and Reinier.
Reposted by Jason Yu
This one is a bit of a departure from the usual and definitely a work in progress!
We found that by using ab initio reconstruction at very high res, in very small steps, we could crack some small structures that had eluded us - e.g. 39kDa iPKAc (EMPIAR-10252), below.
Read on for details... 1/x
We found that by using ab initio reconstruction at very high res, in very small steps, we could crack some small structures that had eluded us - e.g. 39kDa iPKAc (EMPIAR-10252), below.
Read on for details... 1/x
September 13, 2025 at 12:05 AM
This one is a bit of a departure from the usual and definitely a work in progress!
We found that by using ab initio reconstruction at very high res, in very small steps, we could crack some small structures that had eluded us - e.g. 39kDa iPKAc (EMPIAR-10252), below.
Read on for details... 1/x
We found that by using ab initio reconstruction at very high res, in very small steps, we could crack some small structures that had eluded us - e.g. 39kDa iPKAc (EMPIAR-10252), below.
Read on for details... 1/x
Reposted by Jason Yu
🧬 Transcription elongation by RNA polymerase II relies on a web of elongation factors. Our new work shows how IWS1 acts as a modular scaffold to stabilize & stimulate elongation. Fantastic work by Della Syau! www.biorxiv.org/content/10.1...
August 29, 2025 at 10:14 AM
🧬 Transcription elongation by RNA polymerase II relies on a web of elongation factors. Our new work shows how IWS1 acts as a modular scaffold to stabilize & stimulate elongation. Fantastic work by Della Syau! www.biorxiv.org/content/10.1...
Reposted by Jason Yu
Nature research paper: Structural basis for the dynamic regulation of mTORC1 by amino acids
go.nature.com/3V8r3Lw
go.nature.com/3V8r3Lw
Structural basis for the dynamic regulation of mTORC1 by amino acids - Nature
Using cryo-electron microscopy, the interactions of Sestrin2 and CASTOR1 with GATOR2 were resolved, revealing how mTORC1 activation is regulated and how nutrient availability triggers signalling for cellular growth.
go.nature.com
August 24, 2025 at 3:00 PM
Nature research paper: Structural basis for the dynamic regulation of mTORC1 by amino acids
go.nature.com/3V8r3Lw
go.nature.com/3V8r3Lw
Reposted by Jason Yu
Our #CryoET story on how a top antimalarial drug candidate perturbs the native malarial translation machinery is out @natsmb.nature.com🥳 rdcu.be/eBbrH
A massive team effort led by @leonieanton.bsky.social Meseret Haile & Wenjing Cheng in collaboration with Jerzy Dziekan & the Alan Cowman! #TeamTomo
A massive team effort led by @leonieanton.bsky.social Meseret Haile & Wenjing Cheng in collaboration with Jerzy Dziekan & the Alan Cowman! #TeamTomo
Integrated structural biology of the native malarial translation machinery and its inhibition by an antimalarial drug
Nature Structural & Molecular Biology - Integrated structural biology approach leveraging in situ cryo-electron tomography reveals molecular details of the native malarial translation...
rdcu.be
August 18, 2025 at 12:13 PM
Our #CryoET story on how a top antimalarial drug candidate perturbs the native malarial translation machinery is out @natsmb.nature.com🥳 rdcu.be/eBbrH
A massive team effort led by @leonieanton.bsky.social Meseret Haile & Wenjing Cheng in collaboration with Jerzy Dziekan & the Alan Cowman! #TeamTomo
A massive team effort led by @leonieanton.bsky.social Meseret Haile & Wenjing Cheng in collaboration with Jerzy Dziekan & the Alan Cowman! #TeamTomo
Reposted by Jason Yu
Have no fear if you weren't in the packed audience this week for @martinpacesa.bsky.social's awesome seminar, because you can check out the recording 👇
youtu.be/qQihl6If9vU
youtu.be/qQihl6If9vU
BindCraft: one-shot design of functional protein binders
YouTube video by Boston Protein Design and Modeling Club
youtu.be
August 15, 2025 at 8:56 PM
Have no fear if you weren't in the packed audience this week for @martinpacesa.bsky.social's awesome seminar, because you can check out the recording 👇
youtu.be/qQihl6If9vU
youtu.be/qQihl6If9vU
Reposted by Jason Yu
Now out in Structure: Paper on high-resolution #cryoEM using the 100 kV Tundra cryo-TEM by Dimple Karia, Adrian Koh, @abhaykot.bsky.social, @lingboyu.bsky.social, @landerlab.bsky.social and many others. Happy to have contributed to this effort. Check it out:
www.sciencedirect.com/science/arti...
www.sciencedirect.com/science/arti...
Sub-3 Å resolution protein structure determination by single-particle cryo-EM at 100 keV
Cryoelectron microscopy (cryo-EM) has transformed structural biology by providing high-resolution insights into biological macromolecules. We report s…
www.sciencedirect.com
July 30, 2025 at 9:50 PM
Now out in Structure: Paper on high-resolution #cryoEM using the 100 kV Tundra cryo-TEM by Dimple Karia, Adrian Koh, @abhaykot.bsky.social, @lingboyu.bsky.social, @landerlab.bsky.social and many others. Happy to have contributed to this effort. Check it out:
www.sciencedirect.com/science/arti...
www.sciencedirect.com/science/arti...
Reposted by Jason Yu
When particles have orientation bias, the resulting maps are often streaked along the missing directions. In this case study, we cover why orientation bias produces anisotropic #cryoEM maps and how you may be able to recover from it!
guide.cryosparc.com/processing-d...
guide.cryosparc.com/processing-d...
July 23, 2025 at 12:29 PM
When particles have orientation bias, the resulting maps are often streaked along the missing directions. In this case study, we cover why orientation bias produces anisotropic #cryoEM maps and how you may be able to recover from it!
guide.cryosparc.com/processing-d...
guide.cryosparc.com/processing-d...
Reposted by Jason Yu
I am pleased to announce Reactor—the complex formation calculator for multi-component protein complex formation experiments. Developed by the Farnung Lab @harvardmed.bsky.social.
reactor-farnunglab.pythonanywhere.com 1/n
reactor-farnunglab.pythonanywhere.com 1/n
Reactor - The complex formation calculator
reactor-farnunglab.pythonanywhere.com
July 22, 2025 at 1:13 PM
I am pleased to announce Reactor—the complex formation calculator for multi-component protein complex formation experiments. Developed by the Farnung Lab @harvardmed.bsky.social.
reactor-farnunglab.pythonanywhere.com 1/n
reactor-farnunglab.pythonanywhere.com 1/n