Pawel Wydorski
@pwydorski.bsky.social
International graduate student in the US. Biochemistry? Biophysics? Cell biology?! Chaperones, neurodegenerative diseases, all flavours PPIs. Opinions are my own. he/him
Reposted by Pawel Wydorski
Why LLPS Scaffolds Cannot Exist – A Thermodynamic Thread
If you consider arguments logical, please share. Else please expose logical faults
🧵👇
If you consider arguments logical, please share. Else please expose logical faults
🧵👇
November 19, 2025 at 5:48 AM
Why LLPS Scaffolds Cannot Exist – A Thermodynamic Thread
If you consider arguments logical, please share. Else please expose logical faults
🧵👇
If you consider arguments logical, please share. Else please expose logical faults
🧵👇
Reposted by Pawel Wydorski
The review by Banani, Lee, Hyman & Rosen (NRMCB 2017) www.nature.com/articles/nrm... on biomolecular condensates has >6000 citations. It…
1. Introduced a broad definition of “biomolecular condensates,” promoting acceptance that a unifying mechanism may underlie all membrane-less compartments.
1. Introduced a broad definition of “biomolecular condensates,” promoting acceptance that a unifying mechanism may underlie all membrane-less compartments.
Biomolecular condensates: organizers of cellular biochemistry - Nature Reviews Molecular Cell Biology
In addition to membrane-bound organelles, eukaryotic cells feature various membraneless compartments, including the centrosome, the nucleolus and various granules. Many of these compartments form thro...
www.nature.com
November 17, 2025 at 7:24 AM
The review by Banani, Lee, Hyman & Rosen (NRMCB 2017) www.nature.com/articles/nrm... on biomolecular condensates has >6000 citations. It…
1. Introduced a broad definition of “biomolecular condensates,” promoting acceptance that a unifying mechanism may underlie all membrane-less compartments.
1. Introduced a broad definition of “biomolecular condensates,” promoting acceptance that a unifying mechanism may underlie all membrane-less compartments.
Reposted by Pawel Wydorski
Conserved intrinsically disordered region of DNAJB6 dictates its surveillance of FG-Nup condensates
I've been lucky enough to work on this paper of Tessa and Maiara in Veenhoff and Kampinga's lab.
www.biorxiv.org/content/10.1...
I've been lucky enough to work on this paper of Tessa and Maiara in Veenhoff and Kampinga's lab.
www.biorxiv.org/content/10.1...
Conserved intrinsically disordered region of DNAJB6 dictates its surveillance of FG-Nup condensates
Molecular chaperones can prevent protein aggregation and assist proteins in reaching their structurally functional state. The molecular chaperone DNAJB6, a J-domain protein that partners with Hsp70s a...
www.biorxiv.org
October 21, 2025 at 5:54 AM
Conserved intrinsically disordered region of DNAJB6 dictates its surveillance of FG-Nup condensates
I've been lucky enough to work on this paper of Tessa and Maiara in Veenhoff and Kampinga's lab.
www.biorxiv.org/content/10.1...
I've been lucky enough to work on this paper of Tessa and Maiara in Veenhoff and Kampinga's lab.
www.biorxiv.org/content/10.1...
*chef's kiss*
Finally, someone has solved a real problem with AI! No more having to take a paper in the format for a journal that rejected you, and reformat it for a new journal. Well done!! formatmypaper.com
October 15, 2025 at 1:38 PM
*chef's kiss*
Reposted by Pawel Wydorski
Colliding ribosomes are potent signals of cellular stress. But do cells use ‘programmed’ ribosome collisions to regulate gene expression? I’m excited to present a new story from my lab led by Frederick Rehfeld(@fred-rehfeld.bsky.social) which revealed that the answer is YES! Read on to find out how👇
Oxidative stress sensing by the translation elongation machinery promotes production of detoxifying selenoproteins
Selenocysteine, incorporated into polypeptides at recoded termination codons, plays an essential role in redox biology. Using GPX1 and GPX4, selenoenzymes that mitigate oxidative stress, as reporters,...
www.biorxiv.org
October 14, 2025 at 10:28 PM
Colliding ribosomes are potent signals of cellular stress. But do cells use ‘programmed’ ribosome collisions to regulate gene expression? I’m excited to present a new story from my lab led by Frederick Rehfeld(@fred-rehfeld.bsky.social) which revealed that the answer is YES! Read on to find out how👇
Reposted by Pawel Wydorski
new preprint: Ubiquitin is a protein modification linked with degradation but known to regulate other functions. Over 100k ubiquitination sites have been discovered and here we (@julianvangerwen.bsky.social + others) try to prioritize those most critical to the cell www.biorxiv.org/content/10.1...
The functional landscape of the human ubiquitinome
Protein ubiquitination regulates cell biology through diverse avenues, from quality control-linked protein degradation to signaling functions such as modulating protein-protein interactions and enzyme...
www.biorxiv.org
October 9, 2025 at 7:07 AM
new preprint: Ubiquitin is a protein modification linked with degradation but known to regulate other functions. Over 100k ubiquitination sites have been discovered and here we (@julianvangerwen.bsky.social + others) try to prioritize those most critical to the cell www.biorxiv.org/content/10.1...
Reposted by Pawel Wydorski
… unless you’ve heard me talk about it, which I’ve done a lot over the past decade :D Including in this Quanta video: youtu.be/KDQFUmDJ3nY?...
But now this project is finally preprinted!! The answer is skin cells. Skin cells!
www.biorxiv.org/content/10.1...
But now this project is finally preprinted!! The answer is skin cells. Skin cells!
www.biorxiv.org/content/10.1...
October 10, 2025 at 4:47 PM
… unless you’ve heard me talk about it, which I’ve done a lot over the past decade :D Including in this Quanta video: youtu.be/KDQFUmDJ3nY?...
But now this project is finally preprinted!! The answer is skin cells. Skin cells!
www.biorxiv.org/content/10.1...
But now this project is finally preprinted!! The answer is skin cells. Skin cells!
www.biorxiv.org/content/10.1...
Reposted by Pawel Wydorski
15 years in the making, we confirmed that mitochondria - the powerhouse of the cell - have an unusual localization in patients who experience psychosis (including schizophrenia and bipolar disorders). You’ll never guess what kind of patient cells we used to make this discovery… 🧵
October 10, 2025 at 4:47 PM
15 years in the making, we confirmed that mitochondria - the powerhouse of the cell - have an unusual localization in patients who experience psychosis (including schizophrenia and bipolar disorders). You’ll never guess what kind of patient cells we used to make this discovery… 🧵
you should absolutely read "The Melancholy of Resistance" by Laszlo Krasznahorkai
October 9, 2025 at 11:47 AM
you should absolutely read "The Melancholy of Resistance" by Laszlo Krasznahorkai
Reposted by Pawel Wydorski
The proteasome-substrate-shuttle protein UBQLN2 contains—like other quality control system proteins—a long region devoid of lysine (a lysine desert)
Martin Grønbæk-Thygesen (from @rhp-lab.bsky.social) et al show that introducing K here causes ubiquitylation and degradation
doi.org/10.1101/2025...
Martin Grønbæk-Thygesen (from @rhp-lab.bsky.social) et al show that introducing K here causes ubiquitylation and degradation
doi.org/10.1101/2025...
October 7, 2025 at 9:20 PM
The proteasome-substrate-shuttle protein UBQLN2 contains—like other quality control system proteins—a long region devoid of lysine (a lysine desert)
Martin Grønbæk-Thygesen (from @rhp-lab.bsky.social) et al show that introducing K here causes ubiquitylation and degradation
doi.org/10.1101/2025...
Martin Grønbæk-Thygesen (from @rhp-lab.bsky.social) et al show that introducing K here causes ubiquitylation and degradation
doi.org/10.1101/2025...
Reposted by Pawel Wydorski
Preprint alert! 🚨
We reveal molecular switches that enable the nucleolus to reorganise into a proteostasis hub - coordinating protein quality control with ribosome biogenesis and cross-talk with other stress-responsive organelles.
A big tour de force by the team 💪
www.biorxiv.org/content/10.1...
We reveal molecular switches that enable the nucleolus to reorganise into a proteostasis hub - coordinating protein quality control with ribosome biogenesis and cross-talk with other stress-responsive organelles.
A big tour de force by the team 💪
www.biorxiv.org/content/10.1...
CHIP, VCP, and Nucleolar Gatekeepers Remodel the Nucleolus into a Stress-Responsive Proteostasis Hub
The nucleolus, classically dedicated to ribosome biogenesis, also acts as a stress-responsive proteostasis hub. During heat shock, misfolded proteins accumulate in its granular component (GC), but whe...
www.biorxiv.org
October 6, 2025 at 2:19 PM
Preprint alert! 🚨
We reveal molecular switches that enable the nucleolus to reorganise into a proteostasis hub - coordinating protein quality control with ribosome biogenesis and cross-talk with other stress-responsive organelles.
A big tour de force by the team 💪
www.biorxiv.org/content/10.1...
We reveal molecular switches that enable the nucleolus to reorganise into a proteostasis hub - coordinating protein quality control with ribosome biogenesis and cross-talk with other stress-responsive organelles.
A big tour de force by the team 💪
www.biorxiv.org/content/10.1...
My second project from grad school is now out as a preprint: “DnaJB1 chaperone inhibits tau aggregation by recognizing its N-terminus”
For the nerds, below a quick thread with a little bit of context and a couple of interesting observations from this work.
www.biorxiv.org/content/10.1...
For the nerds, below a quick thread with a little bit of context and a couple of interesting observations from this work.
www.biorxiv.org/content/10.1...
DnaJB1 chaperone inhibits tau aggregation by recognizing its N-terminus
A network of protein folding and degradation machineries maintains protein homeostasis by preventing the accumulation of misfolded proteins and by facilitating their clearance. These systems are also ...
www.biorxiv.org
October 3, 2025 at 12:42 PM
My second project from grad school is now out as a preprint: “DnaJB1 chaperone inhibits tau aggregation by recognizing its N-terminus”
For the nerds, below a quick thread with a little bit of context and a couple of interesting observations from this work.
www.biorxiv.org/content/10.1...
For the nerds, below a quick thread with a little bit of context and a couple of interesting observations from this work.
www.biorxiv.org/content/10.1...
Reposted by Pawel Wydorski
I feel some responsibility, as we develop the software. But helical reconstruction is prone to getting stuck in local minima, and unfortunately still requires a lot of self-criticism. The most important one: if you don't see expected features in the map, don't trust it!
September 26, 2025 at 7:47 AM
I feel some responsibility, as we develop the software. But helical reconstruction is prone to getting stuck in local minima, and unfortunately still requires a lot of self-criticism. The most important one: if you don't see expected features in the map, don't trust it!
Reposted by Pawel Wydorski
A single brain infusion of miRNA targeting CAG repeats slows the progression of Huntington's disease by 75% in patients. This is something that I never thought I would see in my lifetime. www.uniqure.com/investors-me...
September 24, 2025 at 1:21 PM
A single brain infusion of miRNA targeting CAG repeats slows the progression of Huntington's disease by 75% in patients. This is something that I never thought I would see in my lifetime. www.uniqure.com/investors-me...
huntingtin out there just parroting tau 🙄
www.science.org/doi/full/10....
www.science.org/doi/full/10....
September 22, 2025 at 9:54 PM
huntingtin out there just parroting tau 🙄
www.science.org/doi/full/10....
www.science.org/doi/full/10....
Reposted by Pawel Wydorski
Massive sibling regression study finds that human traits are largely environmentally driven (average heritability = 0.3)
Within-family heritability estimates for behavioural and disease phenotypes from 500,000 sibling pairs of diverse ancestries
Quantification of the direct effect of genetic variation on human behavioural traits is important for understanding between-individual variation in socio-economic and health outcomes but estimates of ...
www.medrxiv.org
September 20, 2025 at 6:19 PM
Massive sibling regression study finds that human traits are largely environmentally driven (average heritability = 0.3)
Reposted by Pawel Wydorski
Our article on human multidomain protein biogenesis is now published in @natsmb.nature.com
www.nature.com/articles/s41...
www.nature.com/articles/s41...
The human ribosome modulates multidomain protein biogenesis by delaying cotranslational domain docking - Nature Structural & Molecular Biology
By studying dynamic folding intermediates on the human ribosome, Pellowe et al. show that newly made domains help each other to fold but do not stably interact until synthesis is complete, avoiding in...
www.nature.com
September 19, 2025 at 1:52 PM
Our article on human multidomain protein biogenesis is now published in @natsmb.nature.com
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Reposted by Pawel Wydorski
Lipid droplets: Open questions and conceptual advances around a unique organelle. New review from Mike Henne (@hennelab.bsky.social), Emma Reynolds, and William: rupress.org/jcb/article/...
#Biochemistry #CellMetabolism #LipidDroplets
#Biochemistry #CellMetabolism #LipidDroplets
September 18, 2025 at 2:15 PM
Lipid droplets: Open questions and conceptual advances around a unique organelle. New review from Mike Henne (@hennelab.bsky.social), Emma Reynolds, and William: rupress.org/jcb/article/...
#Biochemistry #CellMetabolism #LipidDroplets
#Biochemistry #CellMetabolism #LipidDroplets
Reposted by Pawel Wydorski
And it is worth mentioning that this preprint showed that AF3 ipSAE was found to be the best predictor for experimental success for de novo designed binders:
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
September 16, 2025 at 7:42 PM
And it is worth mentioning that this preprint showed that AF3 ipSAE was found to be the best predictor for experimental success for de novo designed binders:
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Reposted by Pawel Wydorski
Very cool stuff on the co-translational folding of dimers by Sander Tans and his team @amolf-nl.bsky.social:
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Co-translational ribosome pairing enables native assembly of misfolding-prone subunits - Nature Communications
Protein complexes are essential for cell function. Here, authors show that paired ribosomes can help each other’s nascent chains fold correctly, enabling proper dimer assembly and preventing misfoldin...
www.nature.com
August 28, 2025 at 12:07 PM
Very cool stuff on the co-translational folding of dimers by Sander Tans and his team @amolf-nl.bsky.social:
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Reposted by Pawel Wydorski
Origin of Class B J-domain proteins involved in amyloid transactions
Beautiful paper on the origin of Class B JDPs.
www.biorxiv.org/content/10.1...
Beautiful paper on the origin of Class B JDPs.
www.biorxiv.org/content/10.1...
Origin of Class B J-domain proteins involved in amyloid transactions
J-domain protein (JDP) chaperones function widely in proteostasis. Notably, eukaryotic class B JDPs of the cytosol/nucleus prevent assembly or drive disassembly of amyloid aggregates known to cause ne...
www.biorxiv.org
September 14, 2025 at 8:14 PM
Origin of Class B J-domain proteins involved in amyloid transactions
Beautiful paper on the origin of Class B JDPs.
www.biorxiv.org/content/10.1...
Beautiful paper on the origin of Class B JDPs.
www.biorxiv.org/content/10.1...
Reposted by Pawel Wydorski
HSP-1-Specific Nanobodies Alter Chaperone Function in vitro and in vivo https://www.biorxiv.org/content/10.1101/2025.08.25.672099v1
August 27, 2025 at 4:45 AM
HSP-1-Specific Nanobodies Alter Chaperone Function in vitro and in vivo https://www.biorxiv.org/content/10.1101/2025.08.25.672099v1
"tRNA as an assembly chaperone for a macromolecular transcription-processing complex"
www.nature.com/articles/s41...
www.nature.com/articles/s41...
tRNA as an assembly chaperone for a macromolecular transcription-processing complex - Nature Structural & Molecular Biology
Here, the authors solve a series of cryo-electron microscopy structures that show how transfer RNAs (tRNAs) can guide the assembly of the multisubunit poxvirus RNA polymerase, uncovering a role of tRN...
www.nature.com
September 16, 2025 at 1:49 PM
"tRNA as an assembly chaperone for a macromolecular transcription-processing complex"
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Reposted by Pawel Wydorski
Magellon has taken off to explore your cryo-EM data! Now out in @iucrj.iucr.org doi.org/10.1107/S205... Congrats to all involved!
September 5, 2025 at 2:48 PM
Magellon has taken off to explore your cryo-EM data! Now out in @iucrj.iucr.org doi.org/10.1107/S205... Congrats to all involved!