Chris Brooke

Integrated single-cell analyses of affinity-tested B cells enable the identification of a gene signature to predict antibody affinity Chirichella and colleagues integrated single-cell transcriptomics, BCR sequences, and affinity measurements to identify High Signature, a gene expression signature predictive of sub-nanomolar antibodi...

Integrated single-cell analyses of affinity-tested B cells enable the identification of a gene signature to predict antibody affinity @astrazeneca.bsky.social @angelettilab.bsky.social
www.cell.com/cell-systems...

Every social theory undergirding Trumpism has been broken on the steel of Minnesotan resolve. The multiracial community in Minneapolis was supposed to shatter. It did not. It held until Bovino was forced out of the Twin Cities with his long coat between his legs. The secret fear of the morally depraved is that virtue is actually common, and that they’re the ones who are alone. In Minnesota, all of the ideological cornerstones of MAGA have been proved false at once. Minnesotans, not the armed thugs of ICE and the Border Patrol, are brave. Minnesotans have shown that their community is socially cohesive—because of its diversity and not in spite of it. Minnesotans have found and loved one another in a world atomized by social media, where empty men have tried to fill their lonely soul with lies about their own inherent superiority. Minnesotans have preserved everything worthwhile about “Western civilization,” while armed brutes try to tear it down by force.

Last week in Minnesota, I watched ordinary people risk their lives to protect their neighbors. In the process, they not only won a significant—though not final—victory against authoritarianism, they proved virtually every MAGA social theory wrong. (gift link) www.theatlantic.com/ideas/2026/0...

Top CDC vaccine adviser questions need for polio shot, other longstanding recommendations The chair of a federal vaccine advisory panel charted a new course for the committee in a podcast released Thursday, questioning longstanding recommendations.

This is the chair of ACIP. Experimenting on America's kids. HE'S GOT TO GO. “What we’re going to have is a real-world experience of when unvaccinated people get measles,” he said. “What is the new incidence of hospitalization? What’s the incidence of death?” www.statnews.com/2026/01/22/v....

Regulatory hotspot on the influenza A virus polymerase revealed through the structure of the NEP-polymerase complex Structural studies reveal how influenza virus switches between making new RNA genomes and exporting them from the host nucleus.

Beautiful work from @efodor.bsky.social and Jonathan Grimes' labs - the first full structure of the influenza A virus NEP protein, and a clear indication that its role in viral replication is more nuanced that first thought
www.science.org/doi/10.1126/...

Exclusive: key NIH review panels due to lose all members by the end of 2026 Thirteen of the agency’s advisory councils, which must review grant applications before funding is awarded, are on track to have no voting members.

🚨 New from me: Grant review at more than half of NIH's institutes could be frozen by the end of the year.

That's because crucial NIH grant-review panels are slated to be empty at those institutes by Jan 2027.

A wonky bureaucratic problem with big implications.

A short 🧵

Basal IFNλ2/3 signaling is required for ISG expression and viral control in human intestinal epithelial cells Author summary Interferon-lambdas (IFNλs) are antiviral molecules that help protect the surfaces of our body, such as the gut and lungs, from infection. While IFNλs are best known for being produced d...

Excited to share: We show that basal IFNλ2/3 signaling helps human intestinal epithelial cells stay ready for viral infections, even before an acute infection. A reminder that a lot of innate immune defense happens quietly in the background. journals.plos.org/plospathogen...

I came to Minneapolis to report on what's going on, and one of the main questions I showed up with is "just what is the scale of the resistance?" After all, we're all used to the news calling Portland a "war zone" or whatever when it's just some protests in one part of town.

Rhinovirus triggers distinct host responses through differential engagement of epithelial innate immune signaling Rhinoviruses are the most frequent cause of common colds and also a major cause of respiratory distress in high-risk groups. Using single-cell sequencing of rhinovirus-infected nasal epithelial organo...

Rhinoviruses cause common cold & asthma attacks but are also often benign. Using nasal organoids, we learned how the community of cells in the lining the nasal passages coordinates to respond to rhinovirus and which responses lead to excess mucus & inflammation. www.cell.com/cell-press-b...

Minnesota: "School officials say the [5-year-old] child was used as bait. They say [ICE] agents made little Liam knock on the door to ask to be let in in order to see if anyone else was home."

Now live! Nearly all human genes contain multiple transcript isoforms - and the genes that predominantly control infection, ISGs, are no different. Using PacBio with analysis help from Yan Guo, Himadri noticed a never-before-seen transcript isoform of ISG15 that potently restricts flu 1/4

The thing I always come back to is how many people never despaired against longer odds, and how arrogant it would be to put myself above them.

Antibodies elicited by the 2025-2026 influenza vaccine in humans A new H3N2 variant (named subclade K) possesses several key hemagglutinin substitutions and is circulating widely during the 2025-2026 influenza season. In this report, we completed experiments to det...

We find that subclade K viruses are antigenically advanced; however, this year's flu vaccine surprisingly elicited antibodies in many individuals that efficiently recognized these viruses. The implications are clear: go get this year’s vaccine if you haven’t already!

www.medrxiv.org/content/10.6...

If you are submitting an NIH grant in February, you will be required to use SciENcv to prepare you biosketch.

IT IS MUCH WORSE THAN YOU CAN POSSIBLY IMAGINE.

Set aside *at least* 4 hours just to transfer an existing an biosketch into SciENcv.

Why Denmark's vaccine schedule works for Denmark — but not for the United States With its vaccine schedule, “Denmark has made a values choice to accept preventable hospitalizations and illnesses that other countries have chosen to prevent.”

Three weeks ago I explained in @statnews.com why adopting Denmark’s vaccine schedule would leave American children unprotected. Today HHS did it anyway.
www.statnews.com/2025/12/19/d...

Happy to see @joelrc.bsky.social's paper identifying cellular heterogeneity in basal OASL expression as a major determinant of interferon induction during influenza virus infection out in its final form:

www.pnas.org/doi/10.1073/...

Happy new year, hope everyone's 2026 is better than 2025!

Ooof thanks for the heads up

NIH leader resigns after flap over risks of seasonal flu virus study Agency may be expanding list of pathogens subject to dangerous “gain-of-function” regulations

www.science.org/content/arti...

Revisionism in the Wake of Covid A dialogue confronting the premise of revisionist efforts to diminish the pandemic's severity and dismantle public health institutions.

Macedo and Lee misrepresent what happened during the pandemic and are unable to confront Covid's actual toll, presumably because it undermines their premise. A longer take here w/my colleague Greg Gibson:

joshuasweitz.substack.com/p/revisionis...

Global remodeling of ADP-ribosylation by PARP1 suppresses influenza A virus infection - Nature Communications Influenza A virus infection causes a dramatic upregulation of ADP-ribosylation that as part of the cellular antiviral response, a process that is counteracted by the viral NS1 protein.

🧵 Thread on our new @natcomms.nature.com paper: TLDR -- ADP-ribosylation inhibits viral replication and represents a previously under-appreciated arm of innate immunity during flu infection. Read along for the details…. (1/11) www.nature.com/articles/s41...

The Most Feared Person at the NIH Is a Vaccine Researcher Plucked From Obscurity While NIH director Jay Bhattacharya focuses on podcasting, his second in command is dramatically remaking the agency.

www.theatlantic.com/health/2025/...

Put a perspective piece together on how fever may have driven the evolution of antiviral genes: rupress.org/jem/article/...

Thanks!!

This is just a sampling of Liz's findings in the paper, all of which have important implications for how the earliest stages of interferon induction are regulated. Check it out!!

4. IFN induction is quite sensitive to the presence/absence of MAPK/JNK signaling activity.

Consistent with this, treatment with a selective JNK inhibitor completely blocks IFN induction.

3. Intrinsic ISG expression and expression of factors in the MAPK-JNK-AP1 signaling network correlate with IFN induction potential across multiple distinct datasets. This points towards two factors that distinguish those cell capable of producing IFN in response to stimuli from those that are not.

2. Cell-to-cell variation in IFN induction phenotypes is heritable. Single cell clones exhibited ~1000X range in IFN induction phenotypes and this variation was stably maintained through numerous generations.

1. Most cells (in our system) are fully capable of sensing polyI:C, as indicated by clear nuclear translocation of IRF3 - its just that this is insufficient to induce IFN transcription. Other factors are required.

Liz used a variety of approaches (e.g. single cell cloning, pseudotime reconstruction) to examine why only a fraction of cells appear capable of expressing IFN after treatment with the RIG-I ligand polyI:C.

She found a number of cool things, INCLUDING:

Check out @lizthayer.bsky.social's new preprint exploring factors that influence cell-to-cell heterogeneity in interferon (IFN) induction potential!

Intracellular interactions shape antiviral resistance outcomes in poliovirus via eco-evolutionary feedback - Nature Ecology & Evolution A model of intrahost poliovirus replication shows that, after several rounds of replication, pocapavir, a poliovirus capsid inhibitor, collapses viral density, preventing intracellular interactions th...

My first lead author paper is out with Ben Kerr and @alisonfeder.bsky.social! We found that making an antiviral too strong can sometimes make resistance easier to evolve. This has implications for how we design drugs, choose doses, and think about viral evolution in the face of treatment. (1/n)