@jvahokos.bsky.social
Reposted
New preprint🚨
Imagine (re)designing a protein via inverse folding. AF2 predicts the designed sequence to a structure with pLDDT 94 & you get 1.8 Å RMSD to the input. Perfect design?
What if I told u that the structure has 4 solvent-exposed Trp and 3 Pro where a Gly should be?
Why to be wary🧵👇
Imagine (re)designing a protein via inverse folding. AF2 predicts the designed sequence to a structure with pLDDT 94 & you get 1.8 Å RMSD to the input. Perfect design?
What if I told u that the structure has 4 solvent-exposed Trp and 3 Pro where a Gly should be?
Why to be wary🧵👇
December 16, 2025 at 3:15 PM
New preprint🚨
Imagine (re)designing a protein via inverse folding. AF2 predicts the designed sequence to a structure with pLDDT 94 & you get 1.8 Å RMSD to the input. Perfect design?
What if I told u that the structure has 4 solvent-exposed Trp and 3 Pro where a Gly should be?
Why to be wary🧵👇
Imagine (re)designing a protein via inverse folding. AF2 predicts the designed sequence to a structure with pLDDT 94 & you get 1.8 Å RMSD to the input. Perfect design?
What if I told u that the structure has 4 solvent-exposed Trp and 3 Pro where a Gly should be?
Why to be wary🧵👇
Reposted
Oh wow, this is 🤯 amazing: ~3-fold acceleration of running #relion on A100 GPUs for realistic single-particle refinement by the group of Guangwen Yang at @tsinghuauniversity.bsky.social
.
What a fantastic example of #OpenSoftwareAcceleratesScience, literally! 😍
dl.acm.org/doi/full/10....
.
What a fantastic example of #OpenSoftwareAcceleratesScience, literally! 😍
dl.acm.org/doi/full/10....
T2-RELION: Task Parallelism, Tensor Core Accelerated RELION for Cryo-EM 3D Reconstruction | Proceedings of the International Conference for High Performance Computing, Networking, Storage and Analysis
dl.acm.org
November 21, 2025 at 12:32 PM
Oh wow, this is 🤯 amazing: ~3-fold acceleration of running #relion on A100 GPUs for realistic single-particle refinement by the group of Guangwen Yang at @tsinghuauniversity.bsky.social
.
What a fantastic example of #OpenSoftwareAcceleratesScience, literally! 😍
dl.acm.org/doi/full/10....
.
What a fantastic example of #OpenSoftwareAcceleratesScience, literally! 😍
dl.acm.org/doi/full/10....
Reposted
“If there’s ever a year to get a flu vaccine, this is the year.”
Even in years with vaccine mismatches, the flu vaccine consistently prevents severe disease and hospitalizations. Now is the time to get a flu shot if you haven't already, because we will likely have a lot of flu activity this year.
Even in years with vaccine mismatches, the flu vaccine consistently prevents severe disease and hospitalizations. Now is the time to get a flu shot if you haven't already, because we will likely have a lot of flu activity this year.
Mutations in #H3N2 #flu viruses have some experts worried we're facing a second bad #influenza season. The new variant, subclade K, may be able to escape antibodies generated by previous infections or this year's flu shot. But some experts are hedging their bets. www.statnews.com/2025/11/20/f...
Is a bad flu season on the way? Experts see reason to be anxious
There are early indications that this flu season could be a bad one.
www.statnews.com
November 20, 2025 at 2:38 PM
“If there’s ever a year to get a flu vaccine, this is the year.”
Even in years with vaccine mismatches, the flu vaccine consistently prevents severe disease and hospitalizations. Now is the time to get a flu shot if you haven't already, because we will likely have a lot of flu activity this year.
Even in years with vaccine mismatches, the flu vaccine consistently prevents severe disease and hospitalizations. Now is the time to get a flu shot if you haven't already, because we will likely have a lot of flu activity this year.
Reposted
CDC FluView is back, and our fears look like reality.
50.8% of circulating H3N2 viruses belong to the 2a.3a.1-K subclade, which have 2 mutations in a very important antigenic site. Our own 2025-2026 vaccine immunogenicity data will be posted in the next couple of weeks.
www.cdc.gov/fluview/surv...
50.8% of circulating H3N2 viruses belong to the 2a.3a.1-K subclade, which have 2 mutations in a very important antigenic site. Our own 2025-2026 vaccine immunogenicity data will be posted in the next couple of weeks.
www.cdc.gov/fluview/surv...
Weekly US Influenza Surveillance Report: Key Updates for Week 45, ending November 8, 2025
Seasonal influenza activity is low.
www.cdc.gov
November 14, 2025 at 8:33 PM
CDC FluView is back, and our fears look like reality.
50.8% of circulating H3N2 viruses belong to the 2a.3a.1-K subclade, which have 2 mutations in a very important antigenic site. Our own 2025-2026 vaccine immunogenicity data will be posted in the next couple of weeks.
www.cdc.gov/fluview/surv...
50.8% of circulating H3N2 viruses belong to the 2a.3a.1-K subclade, which have 2 mutations in a very important antigenic site. Our own 2025-2026 vaccine immunogenicity data will be posted in the next couple of weeks.
www.cdc.gov/fluview/surv...
Reposted
MISO: microfluidic protein isolation enables single-particle cryo-EM structure determination from a single cell colony.
Or from a single dish of HEK cell culture in the case of two membrane proteins.
Out in Nature Methods now! lnkd.in/gpyBSceg
Wonderful collaboration with the Efremov lab.
Or from a single dish of HEK cell culture in the case of two membrane proteins.
Out in Nature Methods now! lnkd.in/gpyBSceg
Wonderful collaboration with the Efremov lab.
November 14, 2025 at 6:38 PM
MISO: microfluidic protein isolation enables single-particle cryo-EM structure determination from a single cell colony.
Or from a single dish of HEK cell culture in the case of two membrane proteins.
Out in Nature Methods now! lnkd.in/gpyBSceg
Wonderful collaboration with the Efremov lab.
Or from a single dish of HEK cell culture in the case of two membrane proteins.
Out in Nature Methods now! lnkd.in/gpyBSceg
Wonderful collaboration with the Efremov lab.
Reposted
CryoSift is now out @actacrystf.iucr.org doi.org/10.1107/S205... Thanks to all involved. Happy processing!
November 7, 2025 at 4:58 PM
CryoSift is now out @actacrystf.iucr.org doi.org/10.1107/S205... Thanks to all involved. Happy processing!
Reposted
We are looking for a computational postdoc to work with us on new optimisation algorithms to make #RELION even better. Join our bubbly team at the @mrclmb.bsky.social in Cambridge, UK. 🤗 RTs appreciated.
mrc.tal.net/vx/appcentre...
mrc.tal.net/vx/appcentre...
Quick Check Needed
mrc.tal.net
October 29, 2025 at 9:17 AM
We are looking for a computational postdoc to work with us on new optimisation algorithms to make #RELION even better. Join our bubbly team at the @mrclmb.bsky.social in Cambridge, UK. 🤗 RTs appreciated.
mrc.tal.net/vx/appcentre...
mrc.tal.net/vx/appcentre...
Reposted
Just out📢 Our new paper published in @natmicrobiol.nature.com describes highly potent cross-neutralizing human monoclonal antibodies against H5Nx influenza viruses. Close collaboration with Sara Andrews lab and Tongqing Zhou lab at the VRC. Link to the article: rdcu.be/eKV9T 1/2
October 14, 2025 at 3:10 PM
Just out📢 Our new paper published in @natmicrobiol.nature.com describes highly potent cross-neutralizing human monoclonal antibodies against H5Nx influenza viruses. Close collaboration with Sara Andrews lab and Tongqing Zhou lab at the VRC. Link to the article: rdcu.be/eKV9T 1/2
Reposted
I'm proud of our new study showing that some people born in the 1990s have high levels of antibodies that cross-react to H3 viruses from the 1990s and....contemporary H1N1 viruses. Such a surprising story led by Grace Li, in collaboration with many Penn-CEIRR labs. 1/
www.medrxiv.org/content/10.1...
www.medrxiv.org/content/10.1...
Childhood immunological imprinting of cross-subtype antibodies targeting the hemagglutinin head domain of influenza viruses
Influenza virus cross-subtype antibodies targeting the hemagglutinin (HA) head are rare. Here, we found that a large proportion of monoclonal antibodies (mAbs) isolated from individuals immunized with...
www.medrxiv.org
September 26, 2025 at 12:49 PM
I'm proud of our new study showing that some people born in the 1990s have high levels of antibodies that cross-react to H3 viruses from the 1990s and....contemporary H1N1 viruses. Such a surprising story led by Grace Li, in collaboration with many Penn-CEIRR labs. 1/
www.medrxiv.org/content/10.1...
www.medrxiv.org/content/10.1...
Reposted
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
In new study led by @ckikawa.bsky.social, we provide near real-time data on human neutralizing antibody landscape to influenza by measuring ~26,000 titers to >100 recent viral strains
Data can inform vaccine selection & evolutionary/epidemiological modeling
www.biorxiv.org/content/10.1...
Data can inform vaccine selection & evolutionary/epidemiological modeling
www.biorxiv.org/content/10.1...
Near real-time data on the human neutralizing antibody landscape to influenza virus to inform vaccine-strain selection in September 2025
The hemagglutinin of human influenza virus evolves rapidly to erode neutralizing antibody immunity. Twice per year, new vaccine strains are selected with the goal of providing maximum protection again...
www.biorxiv.org
September 8, 2025 at 9:48 PM
In new study led by @ckikawa.bsky.social, we provide near real-time data on human neutralizing antibody landscape to influenza by measuring ~26,000 titers to >100 recent viral strains
Data can inform vaccine selection & evolutionary/epidemiological modeling
www.biorxiv.org/content/10.1...
Data can inform vaccine selection & evolutionary/epidemiological modeling
www.biorxiv.org/content/10.1...
Reposted
Wow!
Covid vaccine development and delivery cost $79.4 billion, but the health and economic benefits of vaccination were valued between $4.83 trillion–$37.8 trillion.
A return on investment of $59.8–$475 per dollar invested!!
This is why vaccine equity matters!
www.medrxiv.org/content/10.1...
Covid vaccine development and delivery cost $79.4 billion, but the health and economic benefits of vaccination were valued between $4.83 trillion–$37.8 trillion.
A return on investment of $59.8–$475 per dollar invested!!
This is why vaccine equity matters!
www.medrxiv.org/content/10.1...
The global return-on-investment of COVID-19 vaccines in the first year of the vaccination programme
COVID-19 vaccines played a critical role in reducing global health burden during the COVID-19 pandemic, but their rapid development required extraordinary effort. This study aims to evaluate their glo...
www.medrxiv.org
September 7, 2025 at 8:58 PM
Wow!
Covid vaccine development and delivery cost $79.4 billion, but the health and economic benefits of vaccination were valued between $4.83 trillion–$37.8 trillion.
A return on investment of $59.8–$475 per dollar invested!!
This is why vaccine equity matters!
www.medrxiv.org/content/10.1...
Covid vaccine development and delivery cost $79.4 billion, but the health and economic benefits of vaccination were valued between $4.83 trillion–$37.8 trillion.
A return on investment of $59.8–$475 per dollar invested!!
This is why vaccine equity matters!
www.medrxiv.org/content/10.1...
Reposted
A laser flash melting procedure, followed by rapid revitrification, provides a simple approach to help mitigate the preferred orientation problem that plagues cryo-EM analysis.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Laser flash melting cryo-EM samples to overcome preferred orientation - Nature Methods
Individual proteins tend to adopt preferred orientations when subjected to vitrification for cryo-electron microscopy analysis. A laser flash melting procedure followed by rapid revitrification provid...
www.nature.com
August 29, 2025 at 6:44 PM
A laser flash melting procedure, followed by rapid revitrification, provides a simple approach to help mitigate the preferred orientation problem that plagues cryo-EM analysis.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Reposted
Another day, another preprint on @biorxivpreprint.bsky.social!
Here, we show how new machine learning tools can be leveraged to design new self-assembling protein nanoparticle immunogens in the absence of experimentally determined structures of the building blocks. www.biorxiv.org/cgi/content/...
Here, we show how new machine learning tools can be leveraged to design new self-assembling protein nanoparticle immunogens in the absence of experimentally determined structures of the building blocks. www.biorxiv.org/cgi/content/...
From sequence to scaffold: computational design of protein nanoparticle vaccines from AlphaFold2-predicted building blocks
Self-assembling protein nanoparticles are being increasingly utilized in the design of next-generation vaccines due to their ability to induce antibody responses of superior magnitude, breadth, and du...
www.biorxiv.org
August 22, 2025 at 5:29 PM
Another day, another preprint on @biorxivpreprint.bsky.social!
Here, we show how new machine learning tools can be leveraged to design new self-assembling protein nanoparticle immunogens in the absence of experimentally determined structures of the building blocks. www.biorxiv.org/cgi/content/...
Here, we show how new machine learning tools can be leveraged to design new self-assembling protein nanoparticle immunogens in the absence of experimentally determined structures of the building blocks. www.biorxiv.org/cgi/content/...
Reposted
Nitric oxide promotes cysteine N-degron proteolysis through control of oxygen availability | Important finding by Kim, Tian, Ratcliffe and Keeley @ox.ac.uk @ispt-proteinterm.bsky.social #N-degron www.pnas.org/doi/10.1073/...
Nitric oxide promotes cysteine N-degron proteolysis through control of oxygen availability | PNAS
Selected proteins containing an N-terminal cysteine (Nt-Cys) are subjected to rapid,
O2-dependent proteolysis via the Cys/Arg-branch of the N-degro...
www.pnas.org
August 20, 2025 at 10:39 AM
Nitric oxide promotes cysteine N-degron proteolysis through control of oxygen availability | Important finding by Kim, Tian, Ratcliffe and Keeley @ox.ac.uk @ispt-proteinterm.bsky.social #N-degron www.pnas.org/doi/10.1073/...
Reposted
Good summary of this very important report @nature.com by @maxkozlov.bsky.social www.nature.com/articles/d41...
August 13, 2025 at 3:19 PM
Good summary of this very important report @nature.com by @maxkozlov.bsky.social www.nature.com/articles/d41...
Reposted
🚨 New paper alert! 🚨
Here we show that stabilized influenza hemagglutinin HPAI H5 immunogens improve the quality of elicited antibody responses. Thank you to @open_phil for funding this work! bit.ly/4lgr0rM
Here we show that stabilized influenza hemagglutinin HPAI H5 immunogens improve the quality of elicited antibody responses. Thank you to @open_phil for funding this work! bit.ly/4lgr0rM
Stabilization of H5 highly pathogenic avian influenza hemagglutinin improves vaccine-elicited neutralizing antibody responses
Transmission of highly pathogenic avian influenza from H5 clade 2.3.4.4b has expanded in recent years to infect large populations of birds and mammals, heightening the risk of a human pandemic. Influe...
bit.ly
August 4, 2025 at 5:48 PM
🚨 New paper alert! 🚨
Here we show that stabilized influenza hemagglutinin HPAI H5 immunogens improve the quality of elicited antibody responses. Thank you to @open_phil for funding this work! bit.ly/4lgr0rM
Here we show that stabilized influenza hemagglutinin HPAI H5 immunogens improve the quality of elicited antibody responses. Thank you to @open_phil for funding this work! bit.ly/4lgr0rM
Reposted
We sequenced the anti-RSV-F antibody 131-2a by mass spec and determined its epitope by cryoEM. New insights in postfusion specific binding and antigenic site I. Now published in ACS Infectious Diseases @pubs.acs.org.
pubs.acs.org/doi/10.1021/...
@xdh.bsky.social @hangryhobbit.bsky.social
pubs.acs.org/doi/10.1021/...
@xdh.bsky.social @hangryhobbit.bsky.social
July 22, 2025 at 11:33 AM
We sequenced the anti-RSV-F antibody 131-2a by mass spec and determined its epitope by cryoEM. New insights in postfusion specific binding and antigenic site I. Now published in ACS Infectious Diseases @pubs.acs.org.
pubs.acs.org/doi/10.1021/...
@xdh.bsky.social @hangryhobbit.bsky.social
pubs.acs.org/doi/10.1021/...
@xdh.bsky.social @hangryhobbit.bsky.social
Reposted
Our paper describing how in-host evolution of a recently emerged, highly pathogenic coronavirus modulates entry into cells, membrane fusion and likely pathogenicity has now been published in its peer-reviewed form!
Led by Ale Tortorici!
@hhmi.org
www.nature.com/articles/s41...
Led by Ale Tortorici!
@hhmi.org
www.nature.com/articles/s41...
Loss of FCoV-23 spike domain 0 enhances fusogenicity and entry kinetics - Nature
The molecular mechanisms of cell entry for the recently identified highly pathogenic feline coronavirus FCoV-23 are characterized in detail.
www.nature.com
July 9, 2025 at 4:25 PM
Our paper describing how in-host evolution of a recently emerged, highly pathogenic coronavirus modulates entry into cells, membrane fusion and likely pathogenicity has now been published in its peer-reviewed form!
Led by Ale Tortorici!
@hhmi.org
www.nature.com/articles/s41...
Led by Ale Tortorici!
@hhmi.org
www.nature.com/articles/s41...
Reposted
Latest preprint from the lab, many years in the making!
By combining #cryoEM with #AlphaFold3 modelling, we propose that norovirus NS3 forms a transmembrane RNA translocase.
This could have big implications for our understanding of viral replication & assembly (🧵)
www.biorxiv.org/content/10.1...
By combining #cryoEM with #AlphaFold3 modelling, we propose that norovirus NS3 forms a transmembrane RNA translocase.
This could have big implications for our understanding of viral replication & assembly (🧵)
www.biorxiv.org/content/10.1...
June 18, 2025 at 6:32 AM
Latest preprint from the lab, many years in the making!
By combining #cryoEM with #AlphaFold3 modelling, we propose that norovirus NS3 forms a transmembrane RNA translocase.
This could have big implications for our understanding of viral replication & assembly (🧵)
www.biorxiv.org/content/10.1...
By combining #cryoEM with #AlphaFold3 modelling, we propose that norovirus NS3 forms a transmembrane RNA translocase.
This could have big implications for our understanding of viral replication & assembly (🧵)
www.biorxiv.org/content/10.1...
Reposted
Our latest preprint is now available doi.org/10.1101/2025...! Led by my postdoc, Luqiang Guo @luqiang.bsky.social, we determined a ~2.4 A resolution structure of the hantavirus glycoprotein tetramer on the surface of VLPs. Also determined structures of dimers of tetramers and Fab-bound tetramers.
June 18, 2025 at 2:24 PM
Our latest preprint is now available doi.org/10.1101/2025...! Led by my postdoc, Luqiang Guo @luqiang.bsky.social, we determined a ~2.4 A resolution structure of the hantavirus glycoprotein tetramer on the surface of VLPs. Also determined structures of dimers of tetramers and Fab-bound tetramers.
Reposted
Excited to present the first review from my lab!
Which mutations allow H5 influenza to jump into humans or other mammals? How close is H5 to a pandemic? This review has the answers and explains the molecular mechanism behind the mutations.
Led by @fcapelastegui.bsky.social.
doi.org/10.1099/jgv....
Which mutations allow H5 influenza to jump into humans or other mammals? How close is H5 to a pandemic? This review has the answers and explains the molecular mechanism behind the mutations.
Led by @fcapelastegui.bsky.social.
doi.org/10.1099/jgv....
June 10, 2025 at 12:44 PM
Excited to present the first review from my lab!
Which mutations allow H5 influenza to jump into humans or other mammals? How close is H5 to a pandemic? This review has the answers and explains the molecular mechanism behind the mutations.
Led by @fcapelastegui.bsky.social.
doi.org/10.1099/jgv....
Which mutations allow H5 influenza to jump into humans or other mammals? How close is H5 to a pandemic? This review has the answers and explains the molecular mechanism behind the mutations.
Led by @fcapelastegui.bsky.social.
doi.org/10.1099/jgv....
Reposted
These new archaeal proteases are great for de novo antibody sequencing by mass spec. Great work by @tshamorkina.bsky.social , Laura and @tkadava.bsky.social together with @hecklab.bsky.social.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
June 2, 2025 at 7:33 AM
These new archaeal proteases are great for de novo antibody sequencing by mass spec. Great work by @tshamorkina.bsky.social , Laura and @tkadava.bsky.social together with @hecklab.bsky.social.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Reposted
In new study led by @timyu.bsky.social, we measure how mutations to H3 flu HA affect cell entry, stability & antibody escape
We find pleiotropic effects of mutations on these phenotypes shape evolution: epistasis alleviates cell-entry but not stability constraints
www.biorxiv.org/content/10.1...
We find pleiotropic effects of mutations on these phenotypes shape evolution: epistasis alleviates cell-entry but not stability constraints
www.biorxiv.org/content/10.1...
Pleiotropic mutational effects on function and stability constrain the antigenic evolution of influenza hemagglutinin
The evolution of human influenza virus hemagglutinin (HA) involves simultaneous selection to acquire antigenic mutations that escape population immunity while preserving protein function and stability...
www.biorxiv.org
May 27, 2025 at 4:23 PM
In new study led by @timyu.bsky.social, we measure how mutations to H3 flu HA affect cell entry, stability & antibody escape
We find pleiotropic effects of mutations on these phenotypes shape evolution: epistasis alleviates cell-entry but not stability constraints
www.biorxiv.org/content/10.1...
We find pleiotropic effects of mutations on these phenotypes shape evolution: epistasis alleviates cell-entry but not stability constraints
www.biorxiv.org/content/10.1...