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joshuapajak.bsky.social
American Cancer Society Postdoctoral fellow and structural biologist in the @briankelch.bsky.social lab at UMass Chan Medical school. I study ATPases and DNA replication/repair. Phage and MD simulations were my first scientific love. he/him/his
20 posts 921 followers 582 following
Prolific Poster

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.

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 [email protected] 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/...

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!

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 🧵👇

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

Please repost! Post-doc studying novel mechanisms of post-replicative gap-filling available in my lab here in beautiful Snowdonia, between July 2025 to end Nov 2026. Generous travel budget. Lab is full of friendly and supportive colleagues. Link below, or DM me/email [email protected] for info

This work is now published in J Phys Chem B! Check out our work showing that simulations predict the impact of distal mutations on kinase-inhibitor binding, and our experimental NanoBRET dataset of 94 kinase mutations that provide a benchmark for future methods. Link: pubs.acs.org/doi/full/10....

Here is the careful look at efficiency DOGE is taking: a recent law school graduate with no science training is deciding what areas are worthy of scientific study 🧪

I had a great time at the Stand Up for Science in Boston today! Great showing from the UMass Chan folks and great overall turnout! If you were there and we didn’t have the chance to say hi, sorry I missed you!

How does MntR function as both repressor and activator with different Mn(II) sensitivity and cooperativity? Led by the remarkable Prof. Shivani Ahuju (Reed), our long-time collaborator Arthur Glasfeld, and Reed undergraduates! #MicroSky #ChemSky #cryoEM www.nature.com/articles/s41...

Happy to share our manuscript on the in situ visualization of the copia retrotransposon in its final form today published in @cellcellpress.bsky.social www.cell.com/cell/fulltex.... What’s new?

Beautiful work 😍

Angiogenin controls angiogenesis (et plus) by nicking tRNAs. But it’s barely active alone. We discovered how 80S ribosome unlocks Ang’s active site and “brings in” tRNAs. Congrats to Anna Loveland and collab. w/@ajplanetearth! https://www.nature.com/articles/s41586-024-07508-8

Mature #HIV-1 contains >2000 copies of “spacer peptide 2”, but we didn’t know why. We now see that SP2 binds the matrix protein and triggers the change into its mature arrangement. Summary video from @margotriggi.bsky.social

Woke up to this….

Injecting arbitrary experimental data into AlphaFold has been a missing feature. With high-throughput crystallography yielding 1000s of structures/year (@covid_moonshot) & cryoET making 😍 but low-res in situ models, it's also become a necessary one for scaling up structural biology. Hence ROCKET👇!

In @justinditrani.bsky.social final postdoc paper (with contributions from many others) we show that forming/purifying vesicles (here from M. smegmatis) allows structure det'n of *endogenous* membrane proteins in their *native lipid bilayer* 🧵 on methods & TB biology... www.pnas.org/doi/full/10....

I'll be presenting my work prospectively studying clinical mutations and their impact on kinase inhibitor binding at #bps2025! Come see my talk on Wednesday morning @ 8:45am.

Three talks from my group on Sunday at #BPS2025 Cryptic pockets in crowded environments 9:30am in Rm 502A Allosteric glues inhibit G proteins noon in Rm 515B Antibody dynamics 5:30pm in Rm 502A

Black chemists you should know about: These inventors, educators, and unsung heroes changed lives through their work in chemistry. cen.acs.org/people/profi... #BlackinChem #BlackHistoryMonth #chemsky🧪

I've been able to brush off most of the erasure of trans people from government websites, but this one is REALLY getting under my skin. It's just complete revisionist history. How fucking dare they Old vs. new

Trump tried to lower NIH indirect rates in his 2017 budget and that failed to pass. This is a reminder that everything he tried to do through legal means in the first term will be attempted again through illegal means. He will only succeed if we let him.

Ever wondered how Pol II speed is controlled during productive elongation? Our study reveals that the helicase RECQL5 triggers transcription braking, while the transcription-coupled DNA repair complex restores the elongation rate. #cryoEM #transcription www.biorxiv.org/content/10.1...

Our paper out @Nature: CARD domains mediate anti-phage defense in bacterial gasdermin systems CARDs are essential for caspase recruitment during human inflammasome activation. We now find them in bacterial immune systems Congrats Tana Wein! Thank you Kranzusch lab! www.nature.com/articles/s41...

Check out our lab’s latest work on the regulation of transcription by RECQL5 helicase! This work was co-led by @alfredo0712.bsky.social and @nlue8.bsky.social, with contributions from Patricia Grob, Ben Kaeser, Jie Fang, and Susanne Kassube. 1/7 www.biorxiv.org/content/10.1...

Congratulations to Jenna Whalen on her Nature Cancer paper out today-a distinct take on nicks and their toxicity! rdcu.be/d60Td

Our #CellLineOfTheWeek is PCNA - illuminating a protein involved in DNA replication and repair! 🧫 Browse our catalog of at-cost #StemCell lines and plasmids: www.allencell.org/cell-catalog... 📦 Distributed by @coriellinstitute.bsky.social and @addgene.bsky.social #FluorescenceFriday

From Dorothea Fiedler's lab: Protein polyphosphorylation as a new post-translational modification www.biorxiv.org/content/10.1...

The Shu complex –a conserved homologous recombination factor– interact with ORC and MCM replication initiation factors to facilitate error-free bypass of replicative DNA damage Kara Bernstein, Katrin Paeschke and coworkers www.embopress.org/doi/full/10....

I'd like to draw your attention to this truly excellent paper from the Taraska lab on cryoET of plasma membrane associated proteins. Everyone who is thinking about probes in the cryoET space should also see what they could do with ferritag (fig 6) www.nature.com/articles/s41...

In a great collaboration with @hummerlab.bsky.social and the Kräusslich lab: HIV capsid doesn't break at the NPC; instead, it cracks open the NPC itself! Details in Cell: authors.elsevier.com/sd/article/S... @mpibp.bsky.social @uniheidelberg.bsky.social A thread below:

New discovery from our #CDlab reported in Cell @cp-cell.bsky.social today: SMC motor proteins have a left-right ‘gearbox’ and can switch direction in DNA loop extrusion! www.sciencedirect.com/science/arti... 1/

How do proteins mis-fold? Paper led by Jacob Aunstrup from Alex Büll’s lab with MD simulations by Abigail Barclay, and key contributions from several others. We combined measurements of Φ-values with MD simulations to study the transition state for amyloid fibril growth doi.org/10.1038/s415...

Wow. This is the first neat paper of 2025! From a baby plate of HEK cells and a uL column

Published in JCIM, #compchem pubs.acs.org/doi/full/10....

So proud of this outstanding team and our new insights into the mechanism of exocyst function in membrane fusion!

Obituary for computational chemistry pioneer Martin Karplus in the New York Times (gift link). #CompChem #ChemSky 🧪 www.nytimes.com/2025/01/13/s...

Many thanks to @aip-publishing.bsky.social! 🧪 They selected our recent #CompChem article about PENSA (with @nj-thomson.bsky.social et al.) to be featured in their showcase on Kudos. Read the plain-language summary here: link.growkudos.com/1e7di3mtb7k