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Our paper on MPP came out in @jbiolchem yesterday. Thanks to the reviewers for improving the manuscript, and thanks to @NSERC_CRSNG and @InnovationCA for supporting this work. sciencedirect.com/science/ar…
Proud to report our latest work on the mechanism of substrate cleavage by the mitochondrial processing peptidase (MPP). Kudos to Andrew Bayne who drove this project, with help from new PhD student Danielle Simons and Naoto Soya in the Lukacs lab. 1/n biorxiv.org/content/10.1101/…
Jean-Francois Trempe retweeted
Join us in congratulating 19 researchers recognized as outstanding peer reviewers! They stand out for completing additional tasks and providing thoughtful, high-quality peer reviews that help ensure the integrity of health research in Canada.
Learn more: cihr-irsc.gc.ca/e/53994.html…
Jean-Francois Trempe retweeted
KRAS-targeting PROTAC drug passes first clinical test nature.com/articles/d41591-0…
Jean-Francois Trempe retweeted
Our review on AI for protein engineering is out now, about this too-fast-moving field full of hype and overclaim, yet one that is having a real impact on the world and can be described in a coherent manner without histrionics
science.org/eprint/666XRGRCV…
Jean-Francois Trempe retweeted
A powerful example of protein abundance regulation.
The degradation rate of p53 determines its abundance.
p53 is special, but regulation by protein degradation is not a special case. It's common:
doi.org/10.1101/2025.02.10.6…
Jean-Francois Trempe retweeted
Le meilleur du Canada : un ambitieux programme de bourses postdoctorales propulsé par la philanthropie
Ce matin, le CUSM et L’Institut de recherche du Centre universitaire de santé McGill (L'Institut) ont officiellement lancé Le meilleur du Canada, un programme de bourses postdoctorales conçu pour attirer de jeunes chercheurs exceptionnels du Canada et du monde entier au sein du plus grand centre de recherche en milieu hospitalier du Québec, et l’un des plus productifs au pays.
L’annonce a été faite lors d’une conférence de presse animée par la Dre Lucie Opatrny, présidente-directrice générale du CUSM, en présence de personnalités du milieu de la recherche, des soins de santé et de la philanthropie. La Dre Rhian Touyz, directrice exécutive et scientifique en chef de l'Institut, a rappelé l’importance d’attirer et de soutenir la prochaine génération de leaders scientifiques et Rémi Quirion, scientifique en chef du Québec, a souligné l’importance du programme pour positionner le Québec comme leader en recherche biomédicale et en santé.
Cette initiative est rendue possible grâce à une collaboration entre L’Institut, le Centre universitaire de santé McGill et ses quatre fondations : Fondation du CUSM, Fondation de l’Hôpital général de Montréal, Fondation de l’Hôpital de Montréal pour enfants et Fondation du cancer des Cèdres.
🔗 Pour en savoir plus : cusm.ca/nouvelles-et-histoir…
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Canada’s Best: an ambitious postdoctoral fellowship program powered by philanthropy
This morning, the MUHC and the Research Institute of the McGill University Health Centre (The Institute) officially launched Canada’s Best, a postdoctoral fellowship program designed to attract exceptional young researchers from Canada and around the world to the largest hospital-based research centre in Québec and one of the most productive in the country.
Announced during a press conference led by Dr. Lucie Opatrny, President and Executive Director of the MUHC, the event brought together prominent figures from across the research, healthcare and philanthropic communities. Dr. Rhian Touyz, Executive Director and Chief Scientific Officer of The Institute, emphasized the importance of attracting and supporting the next generation of scientific leaders, and Rémi Quirion, Quebec’s Chief Scientist, highlighted the program’s role in positioning Quebec as a leader in biomedical research and health.
This initiative is made possible through a collaboration between The Institute, the MUHC and its four foundations: the MUHC Foundation, the Montreal General Hospital Foundation, the Montreal Children’s Hospital Foundation and the Cedars Cancer Foundation.
🔗 To learn more: muhc.ca/news-and-patient-sto…
#LeMeilleurDuCanada #CanadasBest #Recherche #Innovation
@RIMUHC1
Jean-Francois Trempe retweeted
Online Now: Mitochondria as sources and targets of cellular signaling dlvr.it/TQcy31
Jean-Francois Trempe retweeted
De nouvelles données suggèrent que les agonistes des récepteurs du GLP-1, comme l’Ozempic, réduisent le risque de démence 🧠
🔗mcgill.ca/x/53S
@mcgillu | @McGillMed | @LDI_ILD | @IRSC_CIHR
Jean-Francois Trempe retweeted
Among all proteome changes in Alzheimer’s disease (AD), 20S proteasomes stand out.
⬛️ Their abundance strongly declines in AD patients.
=> This decline parallels a reduction in 20S substrate proteins and leads to abnormal protein accumulation in AD.
biorxiv.org/content/10.1101/…
Jean-Francois Trempe retweeted
Synthetic α-synuclein fibrils replicate in mice causing Multiple-system atrophy-like path.
Researchers report hi-res. structural analyses of synthetic α-synuclein fibrils (1B fibrils) that developed glial cytoplasmic inclusions in vivo
nature.com/articles/s41586-0…
Jean-Francois Trempe retweeted
AF2 gives weirdly confident prediction for two helices(left). Why is it so confident,since there nothing to fix them in place?It appears that PDB contains >100 structures of homolog. In them, the end has fixed position due to crystal contact(right). So AF2 just learned it
Jean-Francois Trempe retweeted
For readers interested in the potential to target particular protein isoforms as a way to achieve greater drug specificity, here's a review
rdcu.be/eNiHj
nature.com/articles/s41573-0…
Jean-Francois Trempe retweeted
OpenFold3 is finally out! New fully open-source AF3 reproduction from @open_fold Consortium
Try it out on @tamarindbio now!
The model is released with training code, similar performance to AlphaFold3 on protein-ligand complexes, best performance ever for RNA structure prediction, and the same functionalities of other AlphaFold3 reproductions.
Jean-Francois Trempe retweeted
Many articles reported using an antibody ... that didn’t even bind the key protein in Laflamme’s testing. Those articles had been cited over 3,000 times.
A key question is:
◼️ 𝐂𝐚𝐧 𝐩𝐫𝐨𝐭𝐞𝐢𝐧 𝐛𝐢𝐧𝐝𝐞𝐫𝐬 𝐚𝐜𝐡𝐢𝐞𝐯𝐞 𝐡𝐢𝐠𝐡 𝐬𝐩𝐞𝐜𝐢𝐟𝐢𝐜𝐢𝐭𝐲 𝐟𝐨𝐫 𝐞𝐯𝐞𝐫𝐲 𝐞𝐩𝐢𝐭𝐨𝐩𝐞 & 𝐩𝐫𝐨𝐭𝐞𝐨𝐟𝐨𝐫𝐦?
Jean-Francois Trempe retweeted
Predicting protein-protein interactions in the human proteome
Predicting which human proteins shake hands—and how—is a longstanding bottleneck. Proteins rarely act alone; they assemble into complexes that drive immunity, metabolism, signaling, and disease. But testing hundreds of millions of possible pairs experimentally is slow, expensive, and blind to many weak or transient interactions.
Jing Zhang, Qian Cong, David Baker and coauthors tackle this with a smart AI + data pipeline. First, they amplify evolutionary “clues” by assembling omicMSAs—deep multiple sequence alignments mined from petabytes of raw eukaryotic genomic data—so coevolution across species pops out. Second, they train a fast interaction model, RoseTTAFold2-PPI, not just on scarce complex structures, but on domain–domain contacts distilled from ~200M AlphaFold monomers—a huge synthetic training set that teaches the network what real interfaces look like.
The payoff is big: a proteome-scale screen over ~200M human pairs yields ~18,000 PPIs at ~90% precision (and ~29k at 80%), including ~3,600 not previously reported. The method excels on transmembrane interactions, a class that’s notoriously hard in the lab, and produces 3D complex models—so you don’t just get a yes/no, you see the interface. Mapping human variants onto these models flags ~4,950 PPIs with disease mutations at the contact surface, offering concrete hypotheses for mechanism.
Beyond pairs, the team reconstructs higher-order assemblies and nominates new components for well-studied complexes (e.g., telomere maintenance, GPI-GnT, cilia/flagella machinery), and highlights GPCR partners and mitochondrial modules that have been hiding in plain sight.
Stepping back: this is a credible path toward a computed 3D human interactome—faster, cheaper, and increasingly comprehensive as more genomes and structures arrive. It doesn’t replace experiments; it prioritizes them, focusing bench time where the biology is richest.
Paper: science.org/doi/full/10.1126…
Jean-Francois Trempe retweeted
By integrating ψ maps with ribosome profiling and proteomics, we show that ψ patterning directly affects translation:
• mRNAs with single, isolated ψ sites display higher translation efficiency and robust protein output.
• mRNAs with dense ψ clusters exhibit ribosome pausing, slower elongation, and decoupled mRNA–protein ratios.
ψ layout therefore encodes regulatory information that tunes ribosome dynamics and decoding fidelity.
Jean-Francois Trempe retweeted
Interesting - @LBurbulla & colleagues present α-synuclein pathology & MHC-I elevation in mitochondrial membrane protein–associated neurodegeneration (MPAN) patient-derived neurons which is reduced by acetyl-leucine (@ADssx - you seeing this?)
movementdisorders.onlinelibr…
Jean-Francois Trempe retweeted
'The integrated stress response in the brain: cell type-specific functions in health and neurological disorders'
by David Ho-Tieng, Vijendra Sharma, Nahum Sonenberg, Christos Gkogkas & Arkady Khoutorsky @AKhoutorsky
cell.com/trends/neuroscience…
Jean-Francois Trempe retweeted
My colleague Natalya Naumenko has a great piece summarizing her research on famine in the USSR. The first map below shows the distribution of ethnic Ukranians and the second shows excess mortality in 1933.
Both maps act as a background question -- were ethnic Ukrainians targeted by the regime or did they suffer because most Ukrainians lived in farm-intensive areas (and thus affected by collectivization)?
She points out that Ukraine did produce less in 1933 (the year the famine started) than before but not a scale that is sufficient to explain the millions who died. The casualties were due to the seizure of grain for export purposes (leaving Ukrainians to starve).
But, as she points out, "the famine was created by government policies, but this does not mean that the famine was created intentionally". Very true! Government incompetence is sometimes sufficient and superior as an explanation to malice.
So she then sets forth to prove that every rule has exceptions. She measured all the policies enacted. Collectivization? Happened faster and more intensely where they were ethnic Ukrainians! Seizures (euphemistically called procurements)? More intense in areas with more ethnic Ukrainians! There were deliberate policy steps that made Ukrainians vulnerable to shocks (even small ones) and it was targeted at Ukrainians.
Natalya's piece summary is linked in the next post:








































