Alessandro Scacchetti

@metalsga.bsky.social

Postdoc, Bonasio lab @ University of Pennsylvania. Former PhD student, Becker lab @ LMU Munich. Epigenetics & exotic RNAs.

Seeking a post-doc for the LaJoie lab at the Human Technopole, Milan, Italy! We are looking for candidates from the fields of biochemistry, cell biology, and proteomics, who are interested in studying protein interactions of the nucleus 🤓 lnkd.in/dTG2CgXF

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1/🧵 Can transcription factor condensate formation be explained without phase separation? Our new preprint introduces SPARK, a simulation tool that reproduces condensate behavior (clustering, fusion, FRAP) from diffusion & binding kinetics alone. Movie: 60 sec FRAP sim www.biorxiv.org/content/10.6...

Hey, wouldja look at that! An incredible one man show from Pablo Bora, an amazing postdoc...we used Steven Floor's beautiful REMORA approach (fusing RNA base editors to RBPs, allowing RBP cargo to be identified by edits) to explore RBP-RNA binding in mouse embryos doi: doi.org/10.64898/202...

Probing RNA-protein interactions in the early mouse embryo

The union of two germ cells to form a zygote, and subsequent early embryo development, are marked by radical remodeling of virtually every major class of biomolecules as the specialized germline states give way to the rapid and active growth that marks early development. In recent years, advances in ultra-low input genome-wide methods have enabled systematic analyses of mRNA abundance, and of chromatin organization, throughout early development in a variety of model systems. Here, we extend these efforts to the study of RNA binding protein (RBP) function in early mouse embryos, adapting REMORA 1 -- based on fusing an RNA-editing enzyme to an RBP of interest -- for use in early embryos. We benchmark our approach for several well-studied RBPs, successfully recovering expected features of their RNA cargos, and assayed the RNA cargos for 17 RBPs of interest for early gene regulation. Analysis of changes in mRNA metabolism following knockdowns of the RBPs surveyed here allowed us to identify direct regulatory functions for a subset of RBPs in the early mammalian embryo, including an unanticipated role for the RNA export adaptor Alyref in control of 3 prime polyadenylation sites. Together, our data provide a proof of concept resource for systematically exploring RBP functions in mammalian embryogenesis. ### Competing Interest Statement The authors have declared no competing interest. Eunice Kennedy Shriver National Institute of Child Health and Human Development, https://ror.org/04byxyr05, NIHR01HD099816

doi.org

Excited to share our latest work in Molecular Cell: www.cell.com/molecular-ce... We show that PRC1 condensates exclude SWI/SNF from chromatin, revealing a physical mechanism for how opposing regulators compete to control gene expression. Huge thanks to all collaborators and mentors!

Mutual antagonism between PRC1 condensates and SWI/SNF in chromatin regulation

Niekamp et al. show that biomolecular condensates formed by Polycomb repressive complexes can physically restrict access of the activating remodeler SWI/SNF to chromatin. Establishing this barrier dep...

cell.com

#EMBOBrainEpi has come to a close! The EMBO Workshop 'Brain (epi)genome' took a closer look at the brain’s remarkable cellular diversity 🧠 Thank you to our amazing participants, speakers, and organisers! We hope to see you again at the next edition 👋

A picture depicting the scientific organisers of the conferenceA picture depicting the organisers as well as the three poster prize winnersA picture depicting the interior of the Advanced Training Centre at EMBL Heidelberg

Pro-tip: Before I submit my proposal, I read it again, but after 2 glasses of wine on an empty stomach. Places where it isn't totally clear to you in that state, it not going to be clear to the reviewer. Edit that bit.

Now published in NAR. Thanks to the editor and reviewers who provided a great review experience which certainly improved the paper. urldefense.com/v3/__https:/...

Epididymal extracellular vesicles harbor and convey mRNA to sperm for transfer to zygotes

Abstract. The epididymis plays a critical role in promoting sperm maturation, including remodeling the sperm RNA payload. While small RNAs have been extens

urldefense.com

Colin Conine@colinconine.bsky.social · 12mo ago

New from the lab led by @natrigg.bsky.social. We started by characterizing mRNA in sperm, EVs, and the epithelium across epididymal transit. This revealed evidence that sperm acquire specific mRNAs through fusion with epididymal EVs, which we further established with in vitro co-incubation assays

A deep dive without first defining what they mean by #epigenetics. But that's OK, nice thought-provoking ideas. Gedankenexperiment: if you replace the word "epigenetics" throughout with "transcriptional regulation", now how does it look?

Duncan Sproul@sproullab.bsky.social · 4mo ago

Interesting looking study. Seems they are certainly aligned with the neutral-rebel/rebel-rebel #epigenetics camp by invoking chromatin accessibility and TF binding as an epigenetic memory 🤔 (image credit: @zchiang.bsky.social)