Updated preprint 🧵
We mapped how loss of 23 LSD genes reshapes neuronal proteomes in cortical (iN) and dopaminergic (iDA) neurons
New in v2: We added a computational PPI pipeline assessing KO-dependent vulnerability at the interaction and complex level.

Huge thanks to all the fantastic co-authors and collaborators, especially @harvardcellbio.bsky.social, @harvardcellbio.bsky.social , @wilflinglab.bsky.social, Memorial Sloan Kettering Cancer Center, @citehms.bsky.social @jencwaters.bsky.social, and @hms-iac.bsky.social, @fedegasparoli.bsky.social!

Also check out a fantastic complementary study from the Jeffery Kelly lab! They independently uncover how LLOMe disrupts lysosomes by forming amyloids that may act as seeds for pathological aggregates

🔗 doi.org/10.64898/202...

Huge thanks to all amazing co-authors and collaborators — this work was a true team effort! @mmedina300kv.bsky.social @nanigrotjahn.bsky.social @andschwarz.bsky.social @erin-schuman.bsky.social @sauerkrausi.bsky.social @harperlabhms.bsky.social @sonjawelsch.bsky.social @hummerlab.bsky.social

LLOMe has long been used to study lysosomal damage, yet how it works has remained a mystery.
Using cryo-electron tomography, we show it forms amyloid structures inside lysosomes that mechanically rupture membranes – revealing a new paradigm for lysosomal failure.

🔗 doi.org/10.64898/202...

#CryoET

Thank you Elias!

Many thanks to first authors @emboyle.bsky.social, @sergiocruzleon.bsky.social, @structjavi.bsky.social and Johann Brenner and our fantastic collaborators from the Kraft @kraftlabfr.bsky.social, Hummer @hummerlab.bsky.social, Milles @millessigrid.bsky.social and Hunte labs for all their great work!

In this study we investigate the architecture of aminopeptidase-1 condensates directly inside cells at molecular resolution! We show how transient local structures can mediate phase separation, directly linking amino acid sequence to condensate material properties and biological function.

We are excited to share our new preprint which is now available to read on biorXiv: doi.org/10.64898/202... 🎉🎉🎉

Many thanks to first authors @emboyle.bsky.social, @sergiocruzleon.bsky.social, @structjavi.bsky.social and Johann Brenner and our fantastic collaborators from the Kraft @kraftlabfr.bsky.social, Hummer @hummerlab.bsky.social, Milles @millessigrid.bsky.social and Hunte labs for all their great work!

Yes was absolute fun! Like always a fantastic collaboration.

To degrade or not to degrade: how phase separation modulates selective autophagy Selective macroautophagy/autophagy relies on newly formed double-membrane compartments, known as phagophores, to sequester and recycle diverse cellular components, including organelles, biomolecula...

🔄 Repost because the previous link was broken! To degrade or not to degrade! We put together an Autophagic Punctum with @wilflinglab.bsky.social on our latest paper, take a look if you're interested!
🔗 www.tandfonline.com/doi/full/10....

Looking forward to this fantastic meeting!

Phase separation of initiation hubs on cargo is a trigger switch for selective autophagy - Nature Cell Biology Licheva, Pflaum, Babic, Mancilla et al. show that low-affinity cargo–receptor interactions promote autophagy receptor mobility and condensation of the scaffold protein Atg11 to trigger initiation hub ...

🚨 Paper Alert! We’re starting off the year with our latest publication in @naturecellbiology.bsky.social on the role of phase separation in selective autophagy initiation!
This work was a close and exciting collaboration with
@wilflinglab.bsky.social

🔗 nature.com/articles/s41...
Here's a thread👇

Thanks to all collaborators, a fantastic collaboration with the ‪@kraftlabfr.bsky.social‬, several fun retreats & a special thanks to the first authors Mariya, Jeremy, @riccardobabic.bsky.social, and @heaktor.bsky.social

Our study provides insights into the process of initiation during selective autophagy and offers new ideas for developing approaches to selectively degrade unwanted cellular material by autophagy.

3) Experiments using mammalian cell systems reveal striking similarities where FIP200 (Atg11 homologue) clusters on the cargo surface, connecting the phagophore assembly site to the ER. Changing receptor affinity of p62 within condensates resulted in a degradation defect similar to yeast.

2) The low affinity of the receptor for the cargo also allows the initiation hubs to rearrange and establish organelle contact sites necessary to form the pre-autophagosomal structure. Reconstitution of these features allowed us to transform a viral protein expressed in yeast into a neo-cargo.

1) These low affinity interactions are important for the formation of Atg11 condensates at the cargo surface. Atg11 condensates act as initiation hubs to recruit core autophagy machinery proteins such as Atg1 and Atg9.

What happens if you change the physical properties of an autophagic cargo? By altering the low-affinity interaction of autophagic receptors with or within their cargo, we observed a severe degradation defect in budding yeast.

Phase separation of initiation hubs on cargo is a trigger switch for selective autophagy - Nature Cell Biology Licheva, Pflaum, Babic, Mancilla et al. show that low-affinity cargo–receptor interactions promote autophagy receptor mobility and condensation of the scaffold protein Atg11 to trigger initiation hub ...

Check out our latest publication in @naturecellbiology.bsky.social on the role of phase separation in selective autophagy initiation! This was done in a fantastic collaboration with
‪@kraftlabfr.bsky.social‬

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

Short teaser below 👇👇👇

Please share!

Great opportunity! We are looking for a PhD student to work on novel sample preparation methods for cryo-electron tomography.

Thanks Sascha.

Congrats Mariana!

Twenty-seven scientists become EMBO Young Investigators – Press releases – EMBO The group leaders join an international network of nearly 800 life scientists and receive financial support

Humbled and excited to join the EMBO young investigator community. Congratulations to all and looking forward to meeting you in the future.

www.embo.org/press-releas...

I am humbled to be a part of this amazing community. Thanks to the entire group, including fantastic colleagues and mentors along the way.

Congrats Yasin! That is fantastic. You are much closer to Frankfurt now 😁