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...

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...

"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!)

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...

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 @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

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

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.

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

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

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...

I don't want to alarm anyone, but I think my electron density might be haunted. 💎👻💀

A new engineered regulatory T cell is born. Chimeric anti-HLA receptor regulatory T cells (CHAR Tregs) inhibit antibody production by B cells from HLA sensitized transplant patients, offering a precise approach to tackle antibody-mediated organ rejection. www.frontiersin.org/journals/imm...

If you're a postdoc interested in starting your own group, please consider the Dunn School at Oxford, UK. It's a fantastic department and university for molecular immunology and all aspects of immune research!

Getting so many emails about people wanting to do research in our lab and so many of them are obviously AI enhanced, with oddly specific details and common phrasing. A couple have even had an em dash! Hot tip: if you want to work in somebody's lab, don't send the signal you are intellectually lazy.

Federal agencies hiding out in a bunker

Thrilled to announce our paper, "De novo-designed pMHC binders facilitate T cell-mediated cytotoxicity toward cancer cells," is officially out in @science.org! We used generative AI to build a 'GPS' for immune cells to hunt cancer. Read it here: doi.org/10.1126/scie...

🚨Today, in #NatureCancer, we show that #CAR-T cells and #CAR-NK cells contain the seeds of their own self-destruction. Disruption of a FAS-L/FAS enhances CAR potency against liquid and solid cancers. rdcu.be/exjEy. @mskcancercenter.bsky.social @parkerici.bsky.social

Newest paper from the lab out today (doi.org/10.1084/jem....)! Here, we describe PathMHC, a novel MS-based approach to identify rare pathogen-derived peptides on MHC-I and MHC-II. We apply this to a range of pathogens Mtb, SARS-CoV-2, and Listeria.

My wonderful colleage Colin Kleanthous is raising money for the MND association. Please support Colin in this worthy endeavor! www.justgiving.com/page/colin-k... (Please repost!)

Congratulations to the newly minted structural immunologist Dr. George Gray! George made killer progress quantifying TCR cross-reactivity and built a foundation we'll build on for years. The last of our COVID babies - we will miss him as he goes off to train the next generation! #immunosky

"CASP, the 3-decade-old competition has run out of funding from the U.S. National Institutes of Health (NIH) and will exhaust emergency support from the University of California (UC) Davis... on 8 August. UC Davis has told the two researchers who run the program that their jobs will end in weeks"

Think I might build a little drum kit for my office. @gezelter.bsky.social are you going to be ok with that?

NIH cuts have life and death consequences. How a cancer patient became collateral damage to Trump’s purge of the federal workforce, @carolynyjohnson.bsky.social reports wapo.st/44ntbo4

For non-scientists: the funding rate is somewhere between 7% to ~25% (rare) for NIH or NSF grants, depending on where you are applying. Grants are reviewed by a panel of peers who read the grants, score them, then debate the ratings for 1-2 days to rank them. It is INCREDIBLY competitive already.

Out now in @nathumbehav.nature.com: Cuts to NIH funding will impact the economy and employment nationwide. We visualize these losses and advocate for a theory-driven approach to communicating local, self-relevant impact. w/ @joshuasweitz.bsky.social + SCIMaP team: www.nature.com/articles/s41...

In 2019, NIAID proposed an ambitious scientific network focused on pandemic preparedness, research, and response - the "CREID Network". Ten centers kicked off just as the pandemic was taking off, playing critical roles throughout. We were just notified the whole network is terminated. Reason? 👇

Super postdoc @chadbrambley.bsky.social killing it at the AI/HI Immunoinformatics workshop, telling us about finding molecular mimics of antigenic epitopes. Thanks to @epivax.bsky.social for the invitation and opportunity!

Excited to unveil Boltz-2, our new model capable not only of predicting structures but also binding affinities! Boltz-2 is the first AI model to approach the performance of FEP simulations while being more than 1000x faster! All open-sourced under MIT license! A thread… 🤗🚀

Marcia McNutt has been saying that the US is doing a huge experiment with China as the control. The global scientific community will still produce knowledge. But not being in the lead has bad implications for US flourishing. My column: www.science.org/doi/10.1126/...

Congratulations to the newly minted PhD, Dr. Sarah Catherine Baker Hawthorne! A cell biologist not a structural biologist, and not one of my students but still one of mine :) Super proud dad today. Next step California Science & Technology Policy. 💪🧪💪

#Limelight in the elevator!! Up and down 2 times. #Rush Whoohoo! Elevator music is good in this otherwise crappy timeline.

ASSIGNMENT: COMMENT ON SCHEDULE F 1 week left to comment about Schedule F, potentially making NIH institute and center director essentially political appointees. www.regulations.gov/commenton/OP... 1/n

The fear and depression about this proposed budget are valid. BUT The President does not actually get to set a budget. The President gets to propose one. Congress actually sets it. This is a time to call your reps and make it very clear that these numbers are not acceptable.

Anyone care to place bets on when this changes?

what a great paper/resource from Birnbaum team www.biorxiv.org/content/10.1...

Senator Durbin noted that some (I believe Republican Senators) had indicated the US had been doing more than its share of biomedical research and it was time for other countries take a turn. I felt I had to interrupt to respond...

If your test for ground-breaking discoveries can’t detect the discovery of RNAi, or of CRISPR-Cas9, or the cryoEM resolution revolution or Alphafold2, maybe it’s not a very good test. www.nature.com/articles/d41...

Grateful that Jeremy Berg uses his platform so effectively to fight for US research.

Another week, another NIH Guide with no new funding opportunities. Lost track of the number of weeks now - let's just call it n+1.

NEW ASSIGNMENT...NEW ASSIGNMENT...NEW ASSIGNMENT If you have not commented, DO SO BEFORE JUNE 7th After you have commented (and if you commented before), inform 5 COLLEAGUES, FRIENDS, FAMILY MEMBERS, ETC. and get them to consider commenting as well before June 7th. 3/n

Please comment. The Administration is trying to turn the NIH IC Directors and program staff roles into political appointees that serve at the whim of the President. Imagine if each change in administration brought sweeping changes in professional NIH staff across your favorite ICs.

REMINDER.....REMINDER......REMINDER 3 DAYS LEFT TO COMMENT ON SCHEDULE F 1/n

Please read the whole thread and then make a comment!

Live in the US and feeling helpless about funding cuts? Spend 5 minutes making 5 calls. 5calls.org/issue/nih-ns...

Great PhD opportunity in the group of the amazing Christian Freund at the Freie Universität Berlin. This is in Berlin but potentially collaborative with our own team at Notre Dame as we work to understand molecular recognition in cellular immunity. #immunosky www.bcp.fu-berlin.de/en/chemie/bi...