Claudio Bussi

Claudio Bussi

@claudiobussi.bsky.social

Asst Prof - NTU Singapore interested in the inner workings of cells πŸ”¬ www.bussilab.com

458 Followers 378 Following 49 Posts Joined Nov 2024
3 weeks ago
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π™ˆπ™šπ™’π™—π™§π™–π™£π™šπ™¨ 𝙖𝙣𝙙 π™©π™π™šπ™žπ™§ π™‘π™žπ™₯π™žπ™™π™¨ 𝙖𝙣𝙙 π™₯π™§π™€π™©π™šπ™žπ™£π™¨ π™žπ™£ π™€π™§π™œπ™–π™£π™šπ™‘π™‘π™š π™—π™žπ™€π™œπ™šπ™£π™šπ™¨π™žπ™¨ - Spetses, Greece - May 2026 | Utrecht University Utrecht University

CALLING PHDs AND POSTDOCS! Apply for the 20th FEBS/EMBO summer school on Membranes lipids & proteins in organelle biogenesis! Spend a glorious week with leaders in the field on the beautiful island of Spetses in Greece this May. Registration: spetses2026.sites.uu.nl @embo.org @febspress.bsky.social

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3 weeks ago
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Research Fellow (Cell Biology/Biophysics/Bioengineering/Biochemistry) The Institute for Digital Molecular Analytics and Science (IDMxS), officially launched on 1 December 2022, is a Research Centre of Excellence (RCE) supported by a total investment of around S$160 mill...

We’re hiring!
Looking for a highly motivated Postdoc to join my lab at NTU Singapore.
Interested in decoding the crosstalk between membrane-less and membrane-bound compartments? DM me directly with a brief letter stating how your background fits the role! ntu.wd3.myworkdayjobs.com/Careers/job/...

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1 month ago
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I just checked in at @keystonesymposia.bsky.social #KSMembrane2026 #KSAutophagy2026 Looking forward to it!

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1 month ago
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DNA nanodevices detect an acidic nanolayer on the lysosomal surface - Nature Cell Biology Tan and colleagues develop DNA nanodevices to detect the pH of the lysosomal outer surface, observing an acidic layer generated by TMEM175 that regulates lysosome positioning in response to changes in...

www.nature.com/articles/s41...

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1 month ago
Cathepsin C–Catalyzed Ligation Generates Intralysosomal Amyloid Fibrils from Dipeptide Esters Amyloid fibril-associated endolysosomal dysfunction is implicated in multiple neurodegenerative diseases. We report the rapid generation of intralysosomal amyloid fibrils by simply treating cells with certain dipeptide methyl esters. Cathepsin C mediates the ligation of dipeptides into oligopeptides that, sequence-dependently, self-assemble into amyloid fibrils. Progressive fibril growth, not fibril deposition, mediates lysosomal membrane permeabilization. Cryo-electron tomography studies reveal intralysosomal fibrils and broken lysosomal membranes upon dipeptide treatment. Certain oligopeptide fibril structures are competent to cross-seed the aggregation of neurodegeneration-associated Tau(P301S) at lysosomal sites. Similarly, the degree of lysosomal membrane permeabilization and ESCRT-repair response can be tuned with dipeptide sequence variation. The presented Cathepsin C-dependent amyloid fibril formation approach lends itself toward the development of novel tools to further probe lysosomal biology and pathobiology. ### Competing Interest Statement The authors have declared no competing interest. National Institute on Aging, https://ror.org/049v75w11, RF1AG073418 National Center for Advancing Translational Sciences, https://ror.org/04pw6fb54 Department of Education, USA, P031S240270 Freedom Together Foundation Chan Zuckerberg Initiative (United States), CZII-2023–327779 George E. Hewitt Foundation for Medical Research

www.biorxiv.org/content/10.6...

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1 month ago
Cathepsin-dependent amyloid formation drives mechanical rupture of lysosomal membranes Lysosomal membrane integrity is essential for cellular homeostasis, and its failure drives lysosomal storage disorders (LSD) and neurodegeneration. The dipeptide L-leucyl-L-leucine methyl ester (LLOMe) is widely used to model lysosomal damage, yet its mechanism remains poorly understood. The prevailing view holds that LLOMe polymerizes into membrane-permeabilizing peptide chains within the lysosomal lumen. Using cryo-electron tomography in cultured cells and primary neurons, we visualized the structural basis of LLOMe-induced lysosomal damage. We reveal that LLOMe forms amyloid structures within lysosomes that directly interact with and rupture the limiting membrane through mechanical stress. In vitro reconstitution confirms this amyloid-mediated mechanism. These findings establish a structural paradigm for lysosomal membrane disruption and provide insights into how disease-relevant protein aggregates, implicated in neurodegeneration and LSD, may compromise lysosomal integrity. ### Competing Interest Statement J.W.H. is a co-founder of Caraway Therapeutics, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (Caraway) and is a scientific advisory board member for Lyterian Therapeutics. Aligning Science Across Parkinson's, https://ror.org/03zj4c476, ASAP-000350, ASAP-000282, ASAP-024268 Boehringer Ingelheim Fonds, https://ror.org/00dkye506 Deutsche Forschungsgemeinschaft, https://ror.org/018mejw64, GRK 2566/1 Pew Scholars Program NIH Common Fund, https://ror.org/001d55x84, RF1NS125674, R01NS110395 Fred and Joan Goldberg Post-doctoral Fellowship European Research Council, 101041982

www.biorxiv.org/content/10.6...

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2 months ago
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The membrane transition strongly enhances biopolymer condensation through prewetting - Nature Chemical Biology Biopolymers can couple to membrane lipids and condense to prewet membranes. Here a range of membrane perturbations in reconstituted systems and cells show that the prewetting is sensitive to membrane ...

www.nature.com/articles/s41...

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2 months ago
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TheΒ ATG8 E3-like ligases sense lysosomal damage and initiate ESCRT-mediated membrane repair - The EMBO Journal After damage from pathogenic, chemical or physical stress, endolysosomal membranes are repaired and resealed by the endosomal sorting complex required for transport (ESCRT) machinery, but how this mem...

link.springer.com/article/10.1...

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2 months ago

How does cytoplasmic crowding affect reaction rates? doi.org/10.1016/j.mo...

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2 months ago
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Sense, plug, and seal: proteins as both rapid responders and constitutive barriers supporting organelle compartmentalization | Molecular Biology of the Cell Although organellar compartmentalization is primarily established by the delimiting phospholipid bilayer membranes, the contribution of proteins has been less appreciated. Recently, studies across man...

doi.org/10.1091/mbc....

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2 months ago

Organelles harbour pH gradients https://www.biorxiv.org/content/10.64898/2025.12.12.694065v1

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2 months ago
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GPNMB is a biomarker for lysosomal dysfunction and is secreted via LRRK2-modulated lysosomal exocytosis The secretion mechanism of the Parkinson’s disease risk factor GPNMB highlights lysosomal dysfunction as a disease mechanism.

www.science.org/doi/10.1126/...

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3 months ago

Interested in an interdisciplinary PhD program at the intersection of cell biology, biophysics, and chemistry?
Please check out the available projects at Nanyang Technological University Singapore IDMxS, and feel free to reach out if you are considering applying! idmxs.org/opportunitie...

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4 months ago
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Phagocytosis: a process that shapes immune responses to engulfed meals - Nature Reviews Immunology In this Review, Li and Underhill discuss recent advances in understanding the process of phagocytosis. The authors highlight how phagocytosis is integral for innate immune sensing and explain how the ...

www.nature.com/articles/s41...

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4 months ago

πŸ“― shoutout for this beautiful work by Kenji Maeda’s lab, who mapped 300 lipid species across 6 compartiments of humane cells. Besides uncovering general principles of lipid organization, the paper establishes a framework for exploring how lipid landscapes are regulated in physiology and disease πŸ‘‡πŸΌ

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5 months ago
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New paper - MAPL strikes again! Interested in mitochondrial signalling, inflammation, lysosome biology, pyroptosis, and Parkinson's disease? Have a look, there's something for everyone! Feeling grateful! @mitocollier.bsky.social Funded by #CIHR, @asapresearch.parkinsonsroadmap.org.
rdcu.be/eKKz1 πŸ‡¨πŸ‡¦

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5 months ago

The stunning results have to be credited to my great former and current group members!
@mpici.bsky.social @mangiarotti.bsky.social

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5 months ago

Much needed good news!! Our paper is just out in @jcb.org. We found a crazy antagonistic motor function that explains the elongation/retraction phenotype we see during LRRK2-dependent lysosomal tubulation. I am especially proud of Tsion, Nuria, Mia and Irene's contribution. Check it out!

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5 months ago
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Lysosomes signal through the epigenome to regulate longevity across generations The epigenome is sensitive to metabolic inputs and is crucial for aging. Lysosomes act as a signaling hub to sense metabolic cues and regulate longevity. We found that lysosomal metabolic pathways sig...

www.science.org/doi/10.1126/...

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5 months ago
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Bioimage Analysis Specialist | King's College London

BioImage analysis friends - King's are recruiting for a full-time, permanent facility position! Come and work with fun microscopes and fun people (and me!) - please share! www.kcl.ac.uk/jobs/126345-...

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6 months ago
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CHIP protects lysosomes from CLN4 mutant-induced membrane damage - Nature Cell Biology Lee et al. use an aggregation-prone CLN4 mutant that causes lysosomal damage in neurons and show that in non-neurons, the ubiquitin ligase CHIP prevents CLN4-dependent lysotoxicity via microautophagy.

www.nature.com/articles/s41...

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7 months ago
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Membrane Dynamics, Repair and Disease | Keystone Symposia Join us at the Keystone Symposia on Membrane Dynamics, Repair and Disease, February 2026, in Keystone, with field leaders!

Deadlines are approaching for @keystoneSymposia.bsky.social #Membrane Dynamics, Repair & Disease, this February in Keystone! See scholarship, abstract and discount reg dates: keysym.us/KSMembrane26 #KSMembrane26

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7 months ago
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Membrane Dynamics, Repair and Disease | Keystone Symposia Join us at the Keystone Symposia on Membrane Dynamics, Repair and Disease, February 2026, in Keystone, with field leaders!

I'm excited to speak at @keystoneSymposia.bsky.social #Membrane Dynamics, Repair & Disease, this February! Join me to explore emerging research in Keystone! keysym.us/KSMembrane26 #KSMembrane26

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7 months ago
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Postdoc (4 years πŸ€“) Fellowship Alert! πŸ”¬ Are you a computational biologist passionate about cellular biology and quantitative live-cell imaging? Get in touch to learn more and apply! Full details in the attached flyer.

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8 months ago
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The biophysical requirements that govern the efficient endosomal escape of designed mini-proteins - Nature Chemistry ZF5.3 is a mini-protein that escapes endosomes efficiently. Work to understand the underlying mechanism now reveals that ZF5.3 unfolds at pH values lower than 5.5 through protonation of Zn(II)-bound H...

www.nature.com/articles/s41...

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8 months ago
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Interactions between TTYH2 and APOE facilitate endosomal lipid transfer - Nature The Tweety homologue TTYH2 is identified as the lipid transfer mediator for APOE-containing lipoproteins.

www.nature.com/articles/s41...

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9 months ago
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ATXN3 regulates lysosome regeneration after damage by targeting K48-K63-branched ubiquitin chains The cellular response to lysosomal damage involves fine-tuned mechanisms of membrane repair, lysosome regeneration and lysophagy, but how these different processes are coordinated is unclear. Here we ...

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

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9 months ago
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JIP4 deficiency causes a novel lysosome storage disease arising from impaired cystine efflux Lysosomes break down macromolecules, clear cellular waste and recycle nutrients such as cystine. We describe a novel mechanism whereby JIP4 regulates lysosomal cystine storage by controlling the abundance of cystinosin (CTNS), the transporter responsible for lysosomal cystine efflux. To this end, JIP4, previously characterized as a motor adaptor and kinase signaling scaffold, suppresses TMEM55B-dependent ubiquitylation of CTNS. Loss of JIP4 reduces CTNS protein levels, leading to lysosomal cystine accumulation and lysosomal storage defects that phenocopy loss of CTNS in both human cells and the renal proximal tubules of JIP4 knockout mice. These phenotypes mirror cystinosis, the lysosomal storage disease caused by CTNS loss-of-function. Our findings thus reveal a fundamental process that controls the efflux of lysosomal cystine and has relevance to understanding human disease arising from JIP4 mutations. ### Competing Interest Statement The authors have declared no competing interest. NIH, AG085824, AG062210, R35GM150619 Michael J. Fox Foundation, https://ror.org/03arq3225, ASAP-000580

I am excited to share our new preprint! Led by @laylanassar.bsky.social , we have found a new JIP4-dependent mechanism that controls the efflux of cystine from lysosomes. Our findings have implications for both lysosome biology and human disease: doi.org/10.1101/2025...

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9 months ago
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EndoMAP.v1 charts the structural landscape of human early endosome complexes - Nature A study presents EndoMAP.v1, a resource that combines information on protein interactions and crosslink-supported structural predictions to map the interaction landscape of early endosomes.

www.nature.com/articles/s41...

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9 months ago
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Sequence-based prediction of intermolecular interactions driven by disordered regions Intrinsically disordered regions (IDRs) in proteins play essential roles in cellular function. A growing body of work has shown that IDRs often interact with partners in a manner that does not depend ...

www.science.org/doi/10.1126/...

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