Jim Hurley

Open Call for Expressions of Interest in Max Planck Directorships: Expressions of interest can be submitted until 31 October 2025.

Director at Max Planck - a unique position! The Open Call for Expressions of Interest in Max Planck Directorships is open now and can be submitted by the 31st of October 2025. ➡️ mpg.de/directors - Please share the Open Call among potential candidates.

With boost to NIH budget, Senate panel rejects Trump’s plan to slash agency Republicans on spending committee push back against proposed reorganization and overhead cuts

The National Institutes of Health’s budget, and structure, would be preserved under a Senate bill for the 2026 fiscal year.

It is incredibly exciting for me as a structural biologist who is driven by cell biology questions to see real structures in their cellular context. I'm grateful to Wolfgang Baumeister and his associates who pioneered the approach, and the SCSC at SLAC, Lydia-Marie Joubert, and the rest at SCSC.

Congratulations @kev-in-situ-et.bsky.social and the whole team on in situ cryo-ET images of OA-induced mitochondria damage and Parkin-dependent mitophagy out now tinyurl.com/25b82cp4. We couldn't have done it without in situ guru @wilflinglab.bsky.social and mito guru @samlewis.bsky.social .‬

First highlight...

Senator Capito started of the discussion saying that the bill contains AN INCREASE for NIH.

The details are not available, but the bill will be released ofter the hearing.

This is not a done-deal, but it does show where the Senate is on a bipartisan basis.

You are on a roll!

Shout out to the WSJ journalists who reported on Vought’s impoundment by footnote, causing the White House to walk it back. Impact journalism!!

Aiee. We have also heard lots of rumors about this “multi-year funding” issue, and @baldwin.senate.gov, @drugmonkey.bsky.social, and @jeremymberg.bsky.social have all talked about it.

This is very bad. “One weird budget trick” that will cut the number of grants this year in half! 🧪

And here's a bit of color. (I hate it when bsky inserts black boxes that you don't see till after its too late.)

Structural and cell biology NPG publication two-fer today: lysosome signaling structural biology tinyurl.com/mt3uc96k with @robzonculab.bsky.social and mitophagy initiation tinyurl.com/3rpjyfjt with @martenslab.bsky.social @lazaroulab.bsky.social and @hummerlab.bsky.social

And it's out!

I'm thrilled to share our new paper (Adriaenssens et al., Nat Cell Biol 2025).

This paper describes a new mechanism for the initiation of autophagosome biogenesis.

We found that this WIPI-ATG13-driven pathway is preferentially used by a group of transmembrane autophagy receptors.

The expanding repertoire of ESCRT functions in cell biology and disease - Nature This Review examines recently gained insights into the roles of ESCRT complexes in viral infection, immunity, cancer and neurological disease.

The ESCRT complexes are a fascinating membrane cutting machine with roles in countless cell pathways, but they are also ubiquitous in disease and offer new opportunities as drug targets. See our new review with Alyssa Coyne, Marta Miączyńska, and Harald Stenmark at tinyurl.com/yex3trem

We have a preprint for you

EHD2 forms rings on caveolae necks, in contrast to most EHDs forming helices. We determined its structure on membranes and show that N-term acts as a spacer

By Elena, Vasya @vasiliimikirtumov.bsky.social, Jeff &Oli Daumke www.biorxiv.org/content/10.1...

Thanks, Brett!

Structure and activation of the human autophagy-initiating ULK1C:PI3KC3-C1 supercomplex Nature Structural & Molecular Biology, Published online: 29 May 2025; doi:10.1038/s41594-025-01557-xAutophagy is initiated by the Unc-51-like kinase protein kinase complex (ULK1C) and class III phosphatidylinositol 3-OH kinase complex I (PI3KC3-C1). Here, the authors reveal the structure of the 2:1:1 core of ULK1C and its complex with PI3KC3-C1. ULK1C transitions to a 2:2:2 complex in the presence of PI3KC3-C1, suggesting a mechanism for autophagy induction.

ICYMI: New online: Structure and activation of the human autophagy-initiating ULK1C:PI3KC3-C1 supercomplex

Congratulations!

Fascinating.

Thanks for alerting us. Kevin Rose in the lab recalculated using this option. The plots are sparser but the gist is the same.

We share this analysis not to diminish the excitement around in situ structural biology, but to highlight the importance of rigorous interpretation. These powerful tools demand careful use.

How did this model make it through peer review in @natcellbio.nature.com? As a cell biology journal, it seems the attention went to checking the quality of the cell biology, which is impressive, and much less to the consistency of the cryo-EM and structural metrics.

In doing so, we also reproduced sharp peaks in the FSC at high spatial frequencies -often a sign of overfitting or artifacts when incorrect symmetry is applied.

In our own analysis (tinyurl.com/66we8sn5), we found that in healthy cells, prohibitin is in a predominantly open, asymmetric state. Forcing 11-fold symmetry onto this heterogeneous population can produce densities resembling the published density and replicate the model of the 11-armed octopus.

Prohibitin is a heterodimer of PHB1 and PHB2. Yet there was not enough density to dock 11 PHB1:2 dimers. A asymmetric model consisting of 6 copies of one subunit and 5 of another was docked into the density. This is inconsistent with the symmetry assumptions, raising further structural concerns.

To be convincing, a model should fill the density and should have physically plausible contacts between the subunits, which will hold the subunits in place, like this (rcsb.org 9O6S):

The Lange et al. paper presented a model of the prohibitin complex with 11 well-separated radial spokes, unlike any known structure of homologous proteins - a big warning sign. The shape was like an 11-armed octopus, with large gaps between the spokes and no physical mechanism holding them together.

This is exciting progress. But with new methods come new pitfalls. As Richard Henderson noted in 2013, “one must not underestimate the ingenuity of humans to invent new ways to deceive themselves.”

Cryo-FIB milling and in situ cryo-ET are opening immensely exciting windows to structural-level insight in the cellular context. At the same time, tools like AlphaFold have made protein structure prediction widely accessible.

Problem cryo-ET structure alert. A recent paper by Lange et al. in @natcellbio.nature.com (tinyurl.com/38s6a4dn) reported an unusual-looking model of the prohibitin complex in situ. We asked: how was this structure generated? Our reanalysis offers an explanation: tinyurl.com/mszdtwxx 🧵

First Patient Treated with Personalized CRISPR Therapy, Developed in Just Six Months The first on-demand CRISPR therapy for an infant with a rare metabolic disease developed by the IGI and collaborators around the world.

Never been more proud to be at Berkeley: tinyurl.com/86dpm27d

As one who skips breakfast everyday, this is interesting:

Intermittent fasting reduces alpha-synuclein pathology & functional decline in a mouse model of #Parkinsons

Please speak to your clinician before making any changes to your treatment regime
www.nature.com/articles/s41...