Baker Lab @ Notre Dame

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

I at least now have another reason. 🙌😁🙌

Players who might have seemed the obvious choice for name recognition and a cash grab.

Such amazing grace and humility from Alex and Geddy and the Rush family.

This is going to be amazing.

There's a reason why so many of us cried like babies when Neil passed.

What an amazing way to honor Neil's legacy by selecting someone not in the limelight (at least this scale) - an amazing talent with everything to gain, as opposed to some of the other super talented players who are already widely known and already at the top.

Some thoughts on #Rush touring with a surprising choice of the super talented Anika Nilles for a drummer, instead of some of the bigger names that have been thrown around by everybody but Alex and Geddy over the years.

Neil Peart of course eschewed the limelight.

It's a good day.

Tom Sawyer is now airport music.

Picture of a piece of Hagoromo chalk. The best chalk ever made.

Lecturing on biomolecular equilibria this semester. This is in the classroom. Turns out it 100% lives up to the hype. Amazing stuff.

Image for the TCR cross-reactivity group: The big baddy Titin attacking a magician named A3.

A big chunk of the lab works on TCR cross-reactivity - the subgroup is called TCR-X. They made an image for their T shirts... Well played, TCR-X.
#immunosky

I can

I can

Exciting to see our protein binder design pipeline BindCraft published in its final form in @Nature ! This has been an amazing collaborative effort with Lennart, Christian, @sokrypton.org, Bruno and many other amazing lab members and collaborators.

www.nature.com/articles/s41...