Joshua Pajak

Improving Oversight of Federal Grantmaking By the authority vested in me as President by the Constitution and the laws of the United States of America, and to improve the process of Federal

1. Federal funding for research promotes tech, biomedical, and scientific discovery in the US, and provides training for the sci/tech workforce that has brought immeasurable wealth to the US over the past 75 years.

Today's executive order includes a provision that will obliterate both functions.

Brian took a huge risk taking me on as a postdoc, knowing I would need to be trained in simple things like transforming bacteria to more complex things like protein purification and everything in between. He's cultivated a lab that supports trainee growth & I have been so lucky to train in his lab.

Check out my latest preprint, online now! This is my first first author work from Brian's lab. You can check out the biorxiv and Brian's expertly crafted tutorial below.

Check out this new review (with animations, natch) of mechanisms of licensing origins of DNA replication - a wonderful (and continuing!) collaboration with Bruce Stillman @cshlnews.bsky.social and John Diffley @crick.ac.uk! www.nature.com/articles/s41...

Engineering of ATP synthase for enhancement of proton-to-ATP ratio - Nature Communications FoF1-ATP synthase converts proton motive force into ATP, with the H+/ATP ratio typically ranging from 2.7 to 5. Here, the authors engineered this enzyme to form multiple peripheral stalks, achieving a...

Engineered ATP synthase with multiple a-subunits!

Engineering of ATP synthase for enhancement of proton-to-ATP ratio
www.nature.com/articles/s41...

I miss living right next to the Bulls stadium. What a great team ❤️❤️❤️

Postdoc positions open in my lab (Francis Crick Institute) to study

1. initiation of DNA replication.

2. chromatin replication/epigenetic inheritance.

Great for biochemists, biophysicists and cryo-EM/cryo-tomography scientists.

Deadline 3 August 2025.

crick.wd3.myworkdayjobs.com/External/job...

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… 🤗🚀

I've seen folks talk about how "in four years" they'll be able to get back to their planned projects and I really don't think that's going to work out. People & projects losing funding now will not be able to hit pause and come back once funding is restored. Hard-won progress & capacity will be lost

Last week to apply! #PhD #Chromatin #StemCells #ProteinStructure #Enhancers #Transcription #LineageCommitment

Registration now open for the Midwest Enzyme Chemistry Conference 2025.
Registration Link: lnkd.in/ggHMWrF5
Event Date: September 27, 2025
Location: University of Wisconsin - Milwaukee

It's free to register

Kindly share as we want to grow this amazing community of mechanistic enzymologists.....

How does an unusual heptameric AAA-ATPase translocate fully-folded Rieske protein across the inner mitochondrial membrane?
Cryo-EM & functional data by Roland Beckmann and coworkers show how Bcs1 alternates between different states during its translocation activity.
www.embopress.org/doi/full/10....

An ATM-PPM1D Circuit Controls the Processing and Restart of DNA Replication Forks In response to DNA replication stress, DNA damage signaling kinases inhibit origin firing and promote the remodeling and stabilization of replication forks, leading to a systemic reduction in DNA synt...

New preprint from the lab:

ATM controls fork processing and restart, and the PPM1D phosphatase is needed to properly balance this action of ATM.

Congratulations to @yitingcao.bsky.social @yingzhengwang.bsky.social and Jumana Badar.

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

say it again:

4 million people work in higher ed, the largest employer in 10 states, second largest employer in 10 more, and in 60 of the 100 biggest cities

ROI for NIH and NSF for local economies is conservatively 4x, often close to 10x

demolishing higher education is economic sabotage

I could recognize a Walker A motif fucking ANYWHERE

Are there any other US postdocs who six months ago were dead set on pursuing academia but are now strongly considering a 3-4 year stint in industry? Would love to chat 💬

It’s impossible for me to overstate how much of a rockstar postdoc @emmasedivy.bsky.social is and how great of an advisor @briankelch.bsky.social is. They were the perfect 1-2 punch to do some truly fabulous structural phage work and it’s been a real inspiration to watch this come together.

My wife and I are traveling to Copenhagen and Aarhus next week so any other advice is appreciated, not that either of us would be tempted to try Swedish 😂

So excited to see this out Mark! Beautiful work 😍

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

NEW PREPRINT ALERT!
Thanks to all involved!

Post-doc position is available in Choi laboratory at IU. Our research focuses on the structure and function of viral RNAs & replication. Experience in biochemistry or structural biology (X-ray crystallography & cryoEM) is required. Please send cover letter and CV to kaychoi@iu.edu

Please repost.

Check out our review on DNA end resection! With Raphael Ceccaldi, www.nature.com/articles/s41...

How does enterovirus protease specifically recognize its viral RNA genome?

Hint: It takes two!

Our first post on bluesky - Happy to share our new publication.

Structure of coxsackievirus cloverleaf RNA and 3C protease dimer establishes its RNA-binding mechanism
www.science.org/doi/10.1126/...

PAF15-PCNA assembly exhaustion governs lagging strand replication and replisome integrity Genome replication in eukaryotic cells is surveyed by the S-phase checkpoint, which orchestrates sequential replication origin activation to avoid exhaustion of hitherto poorly defined rate-limiting r...

Thrilled to share our lab's first preprint, led by an exceptional PhD student Gita Chhetri and with the support of wonderful collaborators, we find that replisome function is rate-limited by strand-specific PCNA dynamics. Hope you will enjoy reading.

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

Brief teaser:

I’m so proud of went we have been able to accomplish!

Drosophila follicle showing retrotransposons (pink & yellow) expressed in somatic cells infecting the oocyte

1/ Transposable elements are often called "jumping genes" because they mobilize within genomes. 🧬
But did you know they can also jump 𝘣𝘦𝘵𝘸𝘦𝘦𝘯 cells? 🤯
Our new study reveals how retrotransposons invade the germline directly from somatic cells.
www.biorxiv.org/content/10.1...
A short thread 🧵👇

Structural basis for DNA double-strand break sensing by human MRE11-RAD50-NBS1 and its TRF2 complex The MRE11-RAD50-NBS1 (MRN) complex is a central, multifunctional factor in the detection, signaling and nucleolytic processing of DNA double-strand breaks (DSBs). To clarify how human MRN binds generi...

Happy to share our latest pre-print!
We solved the cryoEM structures of human DNA repair factor MRN bound to DNA and to TRF2. Main work of Yilan, Filiz @filizkuybu.bsky.social and Hengjun. Great collab within the @sfb1361.bsky.social and @genecenter-lmu.bsky.social 🧬🔨
www.biorxiv.org/content/10.1...

More than 2 decades ago the PINK1 protein was found to be linked to Parkinson's disease, but its structure and how it was activated was not known. Until @science.org today. A triumph for cryo-EM and structural biology, introducing new targets for drug intervention.
www.science.org/doi/10.1126/...

@science.org Cryo-EM reveals mechanisms of natural RNA multivalency | Science www.science.org/doi/10.1126/...
#RNAsky #RNAbiology #Cryo-EM