Our most recent work on the “function and evolution” of #nuclear-speckles is now online at Cell @cp-cell.bsky.social
doi.org/10.1016/j.ce...
Read the thread👇 for the highlights of our findings.
I’m thrilled to share that my PhD work has been just published in Cell. After a long and bumpy ride, we uncovered the core function of nuclear speckles -splicing of GC-levelled exons- and traced the evolution of this gene architecture and condensates themselves to amniotes.
We wrote a review on Transposable Elements (TEs) and almost all aspects of TE silencing and their roles in biological processes & disease.
www.nature.com/articles/s41...
⚠️ I am really excited to share the work of Anastasios Balaskas, an excellent PhD candidate in the lab, with the wider world. Tasos made a significant advance: generating a stem cell-based embryo model that contains both posterior and anterior neural tissues of the late-stage gastrulating embryo.
This is a piece that I and @karsten-rippe.bsky.social discussing a lot, and a topic that is very close to my heart. The editors @naturerevgenet.bsky.social gave us the stage to do so, and the final version of our review is now available under this link: rdcu.be/erP1u
A short thread follows 1/n
Check out a technology feature in @nature.com by Elie Dolgin regarding our recent 'Killswitch' publication
www.nature.com/articles/d41...
Thank you for the comments and first impressions by Rick Young, Isaac Klein, @danfengcai.bsky.social @superscijew.bsky.social
@yaotianzhang.bsky.social
Nature research paper: Probing condensate microenvironments with a micropeptide killswitch
https://go.nature.com/4mMlGyc
Work is a collaboration with @matthewkraushar.bsky.social, @aktast.bsky.social and the MPIMG Service Groups FACS, microscopy, sequencing and mass spec, as well as researchers from Austria, the US and Switzerland. Link to the publication:
www.nature.com/articles/s41...
In @nature.com Yaotian Zhang and @henriniskanen.bsky.social from the Hnisz Lab discovered a micropeptide, the "Killswitch," which alters the physical state of biomolecules in condensates. This tool solidifies dynamic, liquid-like droplets, affecting their function.
--> www.molgen.mpg.de/4884827
A bottleneck for studying the biological function of biomolecular condensates is unavailability of tools to selectively probe them within living cells. @nature, researchers report one such tool, showcasing its use in various contexts including disease. www.nature.com/articles/s41...
7/7
In summary, the killswitch is a versatile tool that alters condensate material properties in live cells. It revealed that condensate composition and functions rely on their microenvironments, paving the way for new biology and therapeutic strategies
6/7
In zebrafish embryos, killswitch targeted to transcriptional condensates via NANOG suppressed miRNA transcription. Across models, killswitch reveals functional consequences of changing condensate material property, without dissolving the structures themselves.
5/7
In adenoviral 52K condensates, killswitch reduced dynamics and blocked recruitment of capsid protein IIIa, despite preserved binding interfaces. Viral progeny production dropped >90%. The KS thus uncovers hidden roles of condensate microenvironments for condensate regulation.
4/7
Targeting BRD4::NUT condensates with killswitch disrupted RNA Pol II partitioning and reduced transcription. In NUP98::KDM5A-driven AML cells, killswitch caused proteasome-mediated degradation of fusion condensates and impaired leukemia cell growth.
3/7
To analyze compositional changes, we developed NuFANCI, a FACS-based method to isolate nuclear condensates. Applied to killswitch-targeted nucleoli, mass spectrometry revealed selective depletion of ~20 RNA-binding proteins, demonstrating condensate-material-property–dependent partitioning.
2/7
Using the nanobody system, killswitch can be targeted to a wide range of endogenous condensates, including nucleoli, nuclear speckles, chromocenters, and disease-specific condensates.
1/7
Killswitch (KS) is a non-natural, self-associating micropeptide that can be genetically fused to condensate proteins or recruited via GFP-nanobody. It immobilizes scaffold proteins without affecting soluble pools—letting us perturb condensates selectively in live cells.
Special thanks to the great team that made this work possible: @idamarii.bsky.social Pablo Fernandez-Pernas, Melanie A, Matt C, Alex M, Melanie P-S @nvastenhouw.bsky.social @weitzmanlab.bsky.social @floriangrebien.bsky.social @aktast.bsky.social @molgen.mpg.de @childrensphila.bsky.social
What controls condensate composition and function beyond binding stoichiometry? We show that condensate microenvironments play a key role, and can be probed by a micropeptide killswitch in live cells. www.nature.com/articles/s41... in @nature.com with @yaotianzhang.bsky.social Denes Hnisz & team.
In summary, the killswitch is a versatile tool that alters condensate material properties in live cells. It revealed that condensate composition and functions rely on their microenvironments, paving the way for new biological insights and therapeutic strategies.
5/7
In adenoviral 52K condensates, killswitch reduced dynamics and blocked recruitment of capsid protein IIIa, despite preserved binding interfaces. Viral progeny production dropped >90%. The KS thus uncovers hidden roles of condensate microenvironments for condensate regulation.
4/7
Targeting BRD4::NUT condensates with killswitch disrupted RNA Pol II partitioning and reduced transcription. In NUP98::KDM5A-driven AML cells, killswitch caused proteasome-mediated degradation of fusion condensates and impaired leukemia cell growth.
3/7
To analyze compositional changes, we developed NuFANCI, a FACS-based method to isolate nuclear condensates. Applied to killswitch-targeted nucleoli, mass spectrometry revealed selective depletion of ~20 RNA-binding proteins, demonstrating condensate-material-property–dependent partitioning.
2/7
Using the nanobody system, killswitch can be targeted to a wide range of endogenous condensates, including nucleoli, nuclear speckles, chromocenters, and disease-specific condensates.
Killswitch (KS) is a non-natural, self-associating micropeptide that can be genetically fused to condensate proteins or recruited via GFP-nanobody. It immobilizes scaffold proteins without affecting soluble pools—letting us perturb condensates selectively in live cells.
Special thanks to the great team that made this work possible: @idamarii.bsky.social Pablo, Melanie, Matt, Alex, Melanie P-S. @nvastenhouw.bsky.social @floriangrebien.bsky.social @matthewkraushar.bsky.social @aktast.bsky.social @molgen.mpg.de
Congrats Julian!! 🤩🥳
