Baker Lab @ Notre Dame

A terrible scientist. This is scientific misconduct.

What's also infuriating is that publishing companies could address this. Remind me again what those outrageous publication/subscription fees are used for? Oh I know, nothing that relates to actually improving the peer review and overall publication process.

Ditto no. But this might be the BEST thing since stepping down as an administrator. Morning email dread GONE. That plus zealous use of labels & inbox skipping to send all the boring/hyped-up university stuff to the megahype folder that mostly gets ignored. Course, I still have morning news dread...

Electron density of a proline from a high resolution protein crystal structure, showing the hole in the middle of the ring - a prohole.

Total prohole.

Lab people: "Hey, look at all these cool AI models, AlphaFold, Chai, Boltz, gazillion models per week, blah blah, cool new relationships, experiments schmeriments."

Me, looking at one model: "Huh, arginine and tyrosine in the same volume of space, right where the receptor would sit. Nifty."

Sigh.

Agreed, nobody is off the hook and that's on us as reviewers. But this is an added responsibility for the chair that often doesn't happen. I always took my "facilitate discussion" role seriously, especially when there was divergence and nobody was pipping up.

Yes, but that happens less frequently with study sections over zoom, elevating the importance of the chair in facilitating this.

You can give feedback to CSR on both, although since your knowledge of what exactly went on is circumspect, it's an uphill battle and I suspect it takes a lot of feedback from multiple applicants to resonate.

Pt 1: As noted SROs have outsized influence by choice of ad hocs AND reviewer assignments. While SROs are professionals, they are not all equal. Pt 2: If an app is discussed, the chair should call for discussion on opinionated/divergent reviews if it isn't happening. Not all chairs will do this.

Rush Tribute Project on stage in Indianapolis

Meeting the Rush Tribute Project after the show. Thomas (drummer, right) absolutely nailed it.

Wonderful evening with the Rush Tribute Project in Indianapolis. Absolutely nailed every note. They make it look so easy. Wonderful guys - thank you! #Rush

Always love some tasty double mutant cycles.

Agree, that seems very likely. But it's all so dumb. We've been certifying our other support pages for a couple of years now with digital signatures. There's no reason we couldn't all have been told to put the same boiler plate text at the end of our biosketches then sign off. But efficiency!

Yay. But technical issues? I'm guessing complaints. This whole thing is the perfect definition of make-work. Maybe even worse - they made a problem out of a non-problem.

Thanks Chris and team!

(R21 so not percentiled)

Surprisingly good score of an NIH R21 proposal to study molecular mimics in T cell recognition.

Super surprised and super grateful, to the reviewers and more importantly the talented team and collaborators that made this possible (particularly @chadbrambley.bsky.social). I suppose we'll see how changes to advisory councils and MYF play out...?

It's like the same with predicting T cell epitopes.

Committee Releases Conferenced Defense, Homeland Security, Labor, Health and Human Services, Education, and Related Agencies, and Transportation, Housing and Urban Development, and Related Agencies Bi... United States Senate Committee on Appropriations

The conference (agreement between House and Senate) appropriations bill that includes HHS and NIH was released this morning.

www.appropriations.senate.gov/news/majorit...

1/5

HLA micropolymorphisms confine neoantigen conformational adaptability and guide T cell receptor selectivity T cell receptor (TCR) restriction by highly polymorphic major histocompatibility complex (MHC) proteins is a foundation of cellular immunity. Although the effects of MHC polymorphisms on peptide bindi...

Latest preprint from the team: micropolymorphisms in HLAs tune peptide conformational ensembles, altering structural adaptability & contributing to TCR specificity. Even if static structures & pep affinites are the same, closely related HLAs may not be.
#immunosky

www.biorxiv.org/content/10.6...

Crystallographic Ensembles Reveal the Structural Basis of Binding Entropy in SARS-CoV2 Macrodomain Structure-based drug design has traditionally focused on optimizing static, enthalpic interactions between ligands and proteins or on displacing binding site solvent molecules to entropically favor bi...

New preprint! Entropy drives molecular recognition, yet most structure-based drug design ignores it because it is difficult to measure. X-ray crystallography captures ensembles, not single structures. Can we extract thermodynamically meaningful entropy from them?

www.biorxiv.org/content/10.1...

Why Does A.I. Write Like … That?

"Everything that isn’t a ghost is usually woven." LLMs’ style is hilarious but sobering: They make the curious word choices they do because that’s what most people rate as good writing. (PSA: When you see me using “delve,” “—”, and descriptive triplets, it’s really me!)

Definitely another variable to consider.

They missed the control experiment of someone dressed up as Cobra Commander. And then the mindless god Azathoth at the center of the universe. Pretty much the whole alignment chart. Batman is just one corner.

A man in a Batman costume and a pregnant woman in a crowded subway car, their faces obscured by pixelation. Text on top of the image reads: "Fig. 1: An example of the experimental setting, with Batman and a woman simulating pregnancy stand in a crowded metro"

Science will often take you to unexpected and delightful places. In this study, researchers hypothesized that riders in a crowded subway car would be more likely to offer their seat to a pregnant person if there were someone in the subway car dressed as Batman 🧪🦇

www.nature.com/articles/s44...

Because when I decide to sit around and be lazy, all my socks and other freshly washed laundry start spontaneously organizing into a predictive algorithm that tells me almost ok information half the time, as opposed to slowly adopting an ever more disordered distribution of messy if clean clothes.

w/o validation reports, send it back and say it's not reviewable. Reports should be required (and for many journals are, but that's often ignored). After that it's your prerogative to ask for coordinates, maps, etc. Blows my mind we're still talking about this in 2025, but victims of success, etc.

Hey #immunosky people - anyone got any experience encoding multiple MHC-I binding peptides in APCs using minigenes and care to give some advice?

Viral immunologist taps ‘incredible potential’ of immune system New Fred Hutch Cancer Center viral immunologist Dr. Paul Thomas is working to turn the "incredible potential" of the immune system into real-life diagnostic and therapeutic applications. He studies ho...

Viral immunologist @pgtimmune.bsky.social, who recently joined Fred Hutch's Vaccine and Infectious Diseases Division, aims to harness the "incredible potential" of the immune system to advance diagnostics, vaccines and cancer therapies. bit.ly/3WJVpos

Structural changes from wild-type define tumor-rejecting neoantigens Background Challenges in predicting which neoantigens mediate tumor rejection limit the efficacy of neoantigen vaccines to treat cancers, especially for cancers with a high mutational burden like cuta...

Happy to have been part of this work with Karen Hastings and team at the Univ of Arizona quantifying the impact of structure on neoAg immunogenicity. Kudos to @chadbrambley.bsky.social and the others for their awesome work. Look for modeling to improve neoAg prediction!
jitc.bmj.com/content/13/1...

I'm honored to receive a MacArthur Fellowship. As always, I extend my sincerest thanks to all my wonderful mentors, colleagues, collaborators, admins, and trainees who make this work possible. #MacFellow