Vanni Lab at UNIFR, Switzerland

All trajectories and in Zenodo, get in contact if you have questions!

Happy to share the latest from the lab, led by Daniel Alvarez, in collaboration with @lizconibear.bsky.social‬. In this AA-MD tour-de-force, we delve deep into the mechanism and energetics of lipid uptake by bridge-like lipid transfer proteins, and we learn a few interesting things along the way...

Of course! all trajectories are in Zenodo: doi.org/10.5281/zeno...
If you want more details, just get in touch!

Thanks!!

Altogether, we think that the mechanism of membrane fusion described in the context of NPC assembly here is different from what known for other fusion machineries (e.g. SNAREs, dynamin-like GTPases,…). More details in the manuscript—let us know your thoughts! (13/13)

Finally, phylogenetic analyses showed that Brl1/Brr6 homologues are broadly distributed across eukaryotes, and functional experiments in human cells and fly establish CLCC1 as an NPC fusogen in metazoans, consistent with recent preprints by @olzmannlab.bsky.social, Xiao-Wei Chen‬ and others. (12/13)

We also modelled Brl1 in curved membranes (a vesicle mimicking the INM shape). Same result: Brl1/Brr6 oligomers stably interacting and promoting lipid mixing within the channel. (11/13)

When observed closely, lipid mixing looks like classic hemifusion-like intermediates with exposed lipid-tails (but stabilized within protein rings here). (10/13)

But here is another interesting part: interaction between Brl1 and Brr6 only happens when the membranes are < 10 nm apart. This is also very consistent with previous measurement of these distances in NPC assembly intermediates prior to fusion. (9/13)

We went back to simulations of opposed bilayers, but with protein oligomers in both of them. We observed a gradual decrease in membrane distances to the point of interaction between proteins (Brl1 and Brr6). This interaction results in lipid mixing in the central channel of the rings. (8/13)

This hydrophobic loop motif is highly conserved in fungi, and disrupting this loop halted NPC assembly process. This is telling us that Brl1/Brr6 head-to-head interaction is essential for NPC assembly. (7/13)

Given that both Brl1 and Brr6 are essential, and their interaction has been studied in earlier work, we modeled 16 copies of Brl1 together with 16 of Brr6. We got a 32-mer complex with two subunits of 16-mers of Brl1/Brr6 with a head-to-head interaction mediated by a hydrophobic loop motif. (6/13)

Our MD simulations of ring oligomers of Brl1/Brr6 showed pronounced lipid-remodeling in its vicinity. Could this lipid remodeling be enough to drive fusion of INM-ONM? The answer is NO, based on simulation of two opposed bilayers, with protein in only one of them. (5/13)

AF3 led us to find that both Brl1 and Brr6 tend to self-associate and form multimeric structures that become fully closed rings when 10 or more copies are present. By mutating charged residues at the dimer interface, we showed that this side-by-side oligomerization is critical. (4/13)

We found that Brl1 localizes to NPC assembly sites via an N-terminal nuclear export signal (NES). At that site, Brl1 and Brr6 oligomerize into rings, bridging membranes by interacting through conserved hydrophobic loops, promoting lipid mixing. Continue for more details! (3/13)

Meet Brl1 and Brr6: two highly conserved transmembrane proteins in yeast, localized to the inner (INM) and outer nuclear membranes (ONM), respectively. Both are essential for NPC assembly, and despite their similarity, they are non-redundant. (2/13)

Happy to share the latest work from the lab, led by @mudgal17.bsky.social‬, in collaboration with the Weis lab @ethzurich.bsky.social.
How do nuclear membranes fuse during NPC assembly? We answer this question in our latest work, where we identify a new mechanism for membrane fusion… (1/13)

Congratulations Matthieu!!!!

Hey there!✨I’m thrilled to share that our latest research, in collaboration with the Tontonoz Lab (UCLA), has just been published in Nature Metabolism. Our study explores the fascinating role of polyunsaturated fatty acids in fat storage. Check it out!
@labvanni.bsky.social
@natmetabolism.nature.com

Postdoctoral fellowship in protein biochemistry and biophysics - DTU Chemistry Do you want to contribute to an exciting chemical biology project? This postdoctoral fellowship deals with the synthesis of probes aimed at studying cholesterol transport proteins in health and diseas...

I am looking to hire a protein #biochemist, #biophysicist or structural biologist: efzu.fa.em2.oraclecloud.com/hcmUI/Candid...

- 2-year position working on lipid transport proteins.
- Experience in protein expression, purification and biochemical and biophysical assay development.
Please share!

Lipid Droplets: Cell-Biological Control of Metabolism Lipid droplets are master regulators of nutrient and energy homeostasis, but their functions go far beyond these classical roles: They are important in cellular differentiation and various stress res…

Learn about #LipidDroplet #biology, their role in human disease and more at EMBO Workshop "Lipid Droplets: Cell-Biological Control of #Metabolism" in Sant Feliu de Guíxols, Spain, 21–26 September 2025

Deadline: 10 June 2025

meetings.embo.org/event/25-lip...
#EMBOlipidDroplets #EMBOevents 🧪

Cette année le @cnrs.fr ouvre une Chaire de Professeur Junior "Méthodes de modélisation et simulations moléculaires" pour rejoindre à labo à Toulouse (@laascnrs.bsky.social), Palaiseau (LIX) ou Nancy (LORIA), vous avez jusqu'au 14 juillet pour candidater !
emploi.cnrs.fr/Offres/CPJ/C...

Excited to share the new work from the Carvalho lab @dunnschool.bsky.social! 🎉This was part of my PhD & a collaboration with the @labvanni.bsky.social & Ernst labs!

Big thanks to everyone involved! 🙌 @jcb.org

Read more: doi.org/10.1083/jcb.... (1/2)

Indeed, Marc and Yuta are great!! Happy to have contributed to this story with superstar PhD @cristianrocharoa.bsky.social. For lovers of (polyunsaturated) lipids, mitochondria, fat and molecular mechanisms!

Dietary control of peripheral adipose storage capacity through membrane lipid remodelling Complex genetic and dietary cues contribute to the development of obesity, but how these are integrated on a molecular level is incompletely understood. Here, we show that PPARγ supports hypertrophic ...

Check out two great preprints from the Tontonoz lab, linking LPCAT3-mediated phospholipid remodeling to dietary fat intake and cold response
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...

Structural clues about bridge-mediated lipid transfer Nature Structural & Molecular Biology, Published online: 15 May 2025; doi:10.1038/s41594-025-01552-2Some evolutionarily related proteins function as bridges at contact sites between intracellular membranes to allow bulk flow of phospholipids between them. A structural study provides key insight into how lipids are extracted from the donor bilayer and arranged in the transfer channel.

ICYMI: New online: Structural clues about bridge-mediated lipid transfer

The abstract submission deadline for the 2nd edition of our #EMBOLipidDroplets Workshop (21-26 September 2025) is approaching.

Check out the agenda with an amazing lineup of speakers and submit your abstract before 10 June 2025!

@embo.org
@biologists.bsky.social

meetings.embo.org/event/25-lip...

PFAS surfactants self-assemble into vesicles. Exciting results based on Martini simulations from Bei Yan, highlighted in Nature:
www.nature.com/articles/d41...

Happy to share the latest from the lab, with @lizconibear.bsky.social lab. The title says it all: we identified poorly characterised TMEM170 proteins as lipid scramblases that physically associate in the ER with BLTP1/LPD-3/Csf1. We think this has key implications in lipid transport/homeostasis...

PhD Research Fellow in molecular modeling (279265) | University of Bergen Job title: PhD Research Fellow in molecular modeling (279265), Employer: University of Bergen, Deadline: Sunday, May 4, 2025

We have an open PhD position in molecular modeling to work on the recognition of pollutants by fish receptors. More information and application procedure: www.jobbnorge.no/en/available...

Come and work with us ;)