Vijay Ramani
PI @ Gladstone Institutes & UCSF. Molecular technologies & the genomics / molecular biology / biochemistry of gene regulation. Views here mine & do not represent those of my affiliated institutions.
- No justice, no science. Fuck ICE.
"RNAPII clusters reflect local accumulations of transcriptionally engaged polymerases and do not form through higher-order mechanisms such as phase separation" 😬 www.biorxiv.org/content/10.1... by the @mirlab.bsky.social- [Not loaded yet]
- positive / negative feedback always a possibility though. To extend your analogy --> sound engineers in audience move around the crowd and update speaker output across the space depending on crowd (louder in some cases!). Point still stands but the details genome-wide are probably important too.
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- Oof.
- Modern biology research is biased towards investigating genes that are widely conserved and present in humans. What about genes that ARE widely conserved but NOT present in humans? Can genes missing from humans tell us something about what makes our biology different from that of other animals? 1/8
- Oo send on over the list @reitergroup.bsky.social plz!!!
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- Daniele's lab's work demonstrates clearly the link between loop extrusion and regulated gene expression; context & cell-type matter. Statements like "more about X, less about Y" are only useful if context is specified. Homology search isn't relevant in a post-mitotic cell type.
- Man it would be so cool if, in the year 2025 of our lord, we could all just be chill and celebratory about nice professional things being announced for our colleagues in molecular biology. Unrelated, anyone reading absolute Batman? Bc it slaps.
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- 😧😂
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- Reads straight off the PacBio. HiFiASM. Good man. 😂😂😂
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- We had our wedding afterparty there!!!
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- Woohoo!!!!🎉 🙌🏽💯
- Check it out, Chromatin Kids! Chromatin remodeller does stuff to Transcription Factors! Functions where it is seldom seen! Both decreases and increases chromatin accessibility! How cool is that?
- We (ramani and narlikar labs) see the same thing for ISWI in mESCs (PMID37696956). seems possible (maybe even likely?) that CHD family remodelers are also sensory sensors! cool stuff!
- Density* not sensory, d’oh.
- Congratulations @karalmckinley.bsky.social & lab on their groundbreaking recent preprint establishing + characterizing a chemically inducible model of menstruation in mouse: www.biorxiv.org/content/10.1... My jaw dropped when I heard this presented earlier this year. Incredible.
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- 🙏 spearheaded almost entirely by the inimitable @camille-moore.bsky.social!
- Congratulations @jbuenrostro.bsky.social!!!
- Leading epigenetics researcher and longtime Broad member @jbuenrostro.bsky.social has been named core institute member of the Broad. His lab will study how cells change in response to life experiences, and how those alterations affect health and disease.
- Some (+)ve news to lighten another heavy weekend: our latest preprint (c/o Mattiroli + Ramani labs) is up! www.biorxiv.org/content/10.1... A tour-de-force by 1st authors Bruna Eckhardt & @palindromephd.bsky.social, focusing on chromatin replication. RTs welcome; tweetorial in 3,2...(1/n)
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View full threadWill end w/ huge thank you to @fmattiroli.bsky.social & her team, esp Bruna, who spent time w/ us in SF thx to EMBO fellowship. This work exists bc of *international collaboration* & hard work across big time zone gap. We need MORE of this in the world, not LESS for the love of god.(7/7)
- (8/7) ALSO: co-first author @palindromephd.bsky.social from our group is about to be on the job market, specifically seeking tenure-track liberal arts school teaching positions. You should hire her, period. Happy to share exactly why to anyone interested!
- I'll leave details for interested readers to dive into, but here are two (of many) highlights: (1) 1st views of nucleosome wrapping states generated by the replisome alone (we see underwound nucleosomes!); we suspect this relates to our observations in mammalian cells in PMID39549698.(5/n)
- (2) we observe intrinsic asymmetry in single-molecule fiber structures assembled on lagging and leading strands. This is neither resolved by CAF-1/ASF1, nor addition of active ISWI remodeler (Isw1a). Will be exciting to identify the factors that restore symmetry in reconstituted setting!(6/n)
- Building on pioneering work of Kurat, Diffley & colleagues, Bruna, Inge, & Francesca have implemented the pure reconstitution of replication initiation, elongation and termination on fully chromatinized yeast origins. >70 proteins. Extremely challenging, extremely cool, extremely powerful.(3/n)
- Next where our group came in. We applied our SAMOSA-ChAAT method (PMID37696956) to these reconstituted replication reactions. The method is spiced up even more, allowing us to footprint single chromatin fibers AND identify replicated DNA through strand-specific BrdUTP detection via PacBio.(4/n)
- TL/DR: Working hand-in-hand with the absolutely brilliant scientists of the @fmattiroli.bsky.social group, we use single-molecule footprinting to study nascent chromatin fiber assembly by purely reconstituted yeast replisomes and associated factors.(2/n)
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- My only question is what all is earmarked for sambar and what isn’t 😂😂?
- PRC2 silences genes by adding H3K27me3 at the right spots in the genome. Our model shows how the nucleic acid-binding domain (NBD) of SUZ12 keeps this activity under control, and what happens when you remove it.
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View full threadVEFS: the NBD is gone. RNA binding is rare (small red bubble). Most PRC2 is RNA-free, catalytically active, and binds both CpG and non-CpG sites. Result: diffuse H3K27me3 that dilutes PRC1 away from its normal targets, disrupting gene silencing. Read more in our preprint: tinyurl.com/4yrwftrn
- very cool. quick q: are VEFS phenotypes similar to what weber, crabtree & colleagues observed in PMID34117481 upon BRG1 degradation? Wondering if mSWI/SNF-mediated coactivation in distal cis is somehow constraining PRC2 activity to target sites.
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- Very cool and congrats! Perhaps nucleosome density instructive here? Could maybe explain context-specific effects!
- Honored to receive 1st Place Poster Award 🏆 at the EMBL meeting "Gene Regulation: One Molecule at a Time"! Thank you to all who visited and engaged in exciting discussions. Grateful to the organizers for an excellent event! #EMBLSingleMolecule
- Well deserved!!!
- Fantastic new preprint from my colleague @seth-shipman.bsky.social & lab! Systematic characterization of retron editing across 14 new bacterial species!!
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View full threadI think @elphegenoralab.bsky.social had best response earlier. It’s not quite as simple as that: poison loop extrusion & some genes are clearly impacted as enhancers can’t regulate at long distances. “Range extending” regulatory elements confer extrusion independence by as-yet unknown mechanisms.
- worth looking at the brilliant thesis work of Karissa Hansen from Elphege’s group here: www.biorxiv.org/content/10.1...
- Just keep on doing great work Ryan -- it will work out in the end!
- Delighted to see this out! Fun fact: I actually started my lab @ UCSF w/ goal of understanding tRNA txn regulation, which aligned perfectly w/ @genophoria.bsky.social & Sohail! 6+ years of amazing collaboration & stellar work by Siyu, Albertas, & co & we're making real progress w/ more to come!
- Check out our latest preprint, led by Dr. Siyu Chen, that brings together an amazing team of scientists from several labs ( @vram142.bsky.social, Tavazoie, and Navickas) to tackle a fundamental problem in biology: how do cells regulate expression of their tRNAs? www.biorxiv.org/content/10.1...
- To the top of the "to-read" list. Looks like a heroic amount of work from the Hahn lab (large-scale ChEC-seq compendium!) www.nature.com/articles/s41...
- ...& degrons. Wowow.
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- highly recommend the 1st two episodes of The Studio!
- Let’s fucking go—California Institute for Scientific Research. What can we do to make sure this happens?
- Beautiful work from our colleagues in the Jura & Verba labs here @ UCSF! Cryo-EM structures of PI3Ka / KRas complex in context of lipid nanodiscs. Read on for unexpected dimers & to see how high-rez structural biology w/ the right reconstitutions can inform mechanism! www.biorxiv.org/content/10.1...
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- 🙋🏾♂️
- Here is the peer-reviewed version of our study showing how some TAD borders are essential for gene regulation and development. Loss of a single CTCF motif is sufficient to cause embryonic lethality. www.sciencedirect.com/science/arti...
- congratulations pedro!! Beautiful work as usual, and just another testament to the strength of our country's intramural science program.
- A thread. Things are bad. But we’ve already lost if they smother the passion & joy we have for science. So here’s a proposal: if you’re a biologist in any way impacted by *exasperated wave* & want to chat, drop me an e-mail at myfirst.mylast[at]ucsf.edu. Let’s schedule a 30min chat about [...] (1/n)
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View full threadYes things are bad, & no we cannot put our heads in the sand & pretend things will revert back to the status quo (seems...unlikely!). But in addition to outward action (call your congresspeople, protest, support your local education / outreach programs), [...] (4/n)
- [...] we deserve to feed our passion for science. To me, part of that is reinforcing the amazing community we have, via ideation & discussion. To the few that actually read this thx for attending this TedTalk, & h/t to @arjunraj.bsky.social for inspiring this. (5/5)
- [...] the science you are / will soon be working on, what you’re passionate about, & what your hopes are moving forward. Maybe it leads to a new scientific opportunity; maybe it helps remind you how important your work really is; maybe it isn’t helpful at all. Still worth a shot. (2/n)
- Talking with my colleagues @ Gladstone and UCSF over the last week, I’ve felt invigorated by folks’ commitment to pushing research ever forward. It’s reminded me of one of the jobs of the basic scientists: find solutions to nearly impossible problems, at the very boundary of what is known. (3/n)
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- Just say the quiet part out loud. They’re killing *people*.
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- 🤔🤨
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- thanks yan! Your work as well, congratulations 😀! Let's get a coffee once you've arrived & settled here in the bay!
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- nothing if not consistent 😂
- What about *in vivo*? W/ a mouse model from Zaret group, assessed how perturbed FOXA2 (single mutant allele defective for histone binding) influences nuc structure. Replacing just one allele w/ defective copy led to reproducible shifts in nuc structure in murine hepatocytes in vivo! (9/n)
- Extremely proud of Marty & co-authors for putting this together. There's so much in data from SAMOSA/Fiber-seq/etc. waiting to be unraveled w/ right analyses. We hope IDLI "bridges" gaps between structural & genomic methods, while enabling new inquiries into chromatin fiber regulation. (10/10)
