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just posted it as a reply under the main post - sorry about that!

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Link in the main post was cut off! www.biorxiv.org/content/10.6...

biorxiv.org

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a scene from schitts creek shows a woman crawling into a pile of luggage

13/13 we're interested in whether packing and spatial constraint might be a general mechanism setting limits for organelle morphology, interactions, & whole-cell anatomy patterns across contexts. If you've ever seen things to suggest so, please share! Many thanks to our collabs & y'all for reading!

media.tenor.com

ALT: a scene from schitts creek shows a woman crawling into a pile of luggage

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12/13 So: simple mechanical packing can largely explain the interplay between vacuoles and nuclei, independent of contact sites or complex molecular regulation. But looking at whether adhesion or cytoplasmic space may still be crucial factors. stay tuned & suggestions welcome!

11/13 When vac and nuc bending energies match, the effect of vac size on nuc morphology is partially recapitulated, but when the vac is more rigid than the nuc, these simple physical interactions are able to recreate our SXT results - the nucleus loses size scaling & is displaced and flattened.

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10/13 But when push comes to shove, what determines which organelle squishes the other? Honor Akenuwa & Chris Lee (UCSD) built a 2D model demonstrating a range of equilibrium morphologies as a minimization of osmotic pressure and mechanical parameters setting organelle size and shape.

Simulation diagram showing the physical parameters of nucleus, vacuole, and cell

a penguin is standing on top of a purple ball with the word squish underneath it

9/13 All together, this points to spatial constraint - either by a huge vacuole eating up cytoplasmic space, or organelles arranged such that they are packed up against the inner wall of the cell - impacting the morphology, size regulation, and physical interaction between the nucleus and vacuole

media.tenor.com

ALT: a penguin is standing on top of a purple ball with the word squish underneath it

8/ This showed a few things. 1. size scaling is the biggest contributor. 2. vac/nuc size, position, & shape co-vary. Shape effects are stronger in large-vac cells. 3. shape variation is related to organelle position relative to cell axes. What do you see? (top 5 PCs, pink-N, grn-V. L-R: X,Y,Z)

7/13 We adapted the @alleninstitute.org integrated modeling pipeline to model cell, nucleus, and vacuole shapes using spherical harmonics and represent their joint variation in a 5C PCA shape space, showing which features co-vary & contribute most to variance in the dataset

Schematic of integrated shape modeling strategy

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6/13 It appears that the degree of vacuole expansion drives progressive effects on the nucleus - at lower levels it breaks nucleocytoplasmic size scaling and displaces the nucleus toward the cell periphery, and at high levels we start to see effects on nuclear shape.

Gallery of cells of increasing Vacuole:Cell volume ratio

5/13 What determines this "shape competition"? Lack of surrounding space, intrinsic mechanical properties, or maybe both? we look at normal cells & some with enlarged vacuole. When the vacuole dominates the cellular space, what happens to other organelles in response, like the nucleus?

Examples of vacuole enlargement from Gary et al 1998, Iossifides et al 1980, Larson et al 2024

4/13 Now, we zero in on the mesoscale vacuole-nucleus interaction. The 2 largest organelles are linked by the NVJ and interact in many processes. But if you just look at their shapes, there's something else going on - sometimes the vac is indented at interface, sometimes the nuc is deformed.

3D images of vacuole and nucleus in yeast from Larabell & Le Gros 2004 and Perktold et al 2007

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3/13 Last year, we published the largest-yet SXT whole-cell yeast dataset w/ the Larabell group- 490 cells at 30nm isotropic resolution, multiple organelles auto-segmented & tools for quant morphological analysis - OG bluetorial bsky.app/profile/wall... & paper in MBoC doi:10.1091/mbc.E24-10-0486

2/13 A nice model system for this geometric question is budding yeast - simple rigid shape, easy to synchronize, and amenable to whole-cell imaging and reconstruction with high throughput.

whole-cell reconstruction of budding yeast Uchida et al 2011, Wei et al 2012, and Kichuk et al 2024

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Itai Yanai @itaiyanai.bsky.social · 19/12/2025

1/13 So excited to share our new preprint!! How do organelles pack together in a crowded cytoplasm? we know organelles interact via contact sites, but how does competition for space contribute to organelle morphology and interactions? @wallaceucsf.bsky.social www.biorxiv.org/content/10.6...

Images of packed cellular interiors from Maritan et al 2022 and Heinrich et al 2021.

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Reposted by Mary Mirvis

Doing a PhD is - at heart - one long discussion with your mentor. The discussion changes over time - with unexpected turns and ups & downs - but through it all is a pair of people discussing a topic endlessly to make sense of it. PhD students: choose someone you like to talk to!

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Mary Mirvis @marymirvis.bsky.social · 19/12/2025

Exciting, can't wait to see all the new insights this work will unlock, congrats!!

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Mary Mirvis @marymirvis.bsky.social · 17/12/2025

This is so cool!! Any thoughts on what the hotspots might correspond to? Also would it be possible to image the reporter at this resolution in two+ organelles simulateously? if you catch my drift lol

Yamuna Krishnan @krishnanyamuna.bsky.social · 17/12/2025

Reposted by Mary Mirvis

Organelles do NOT have a single uniform pH. And if you think they must, because “protons diffuse fast,” this paper is for you. A thread on why that assumption is wrong; and what we found instead. 🧵 1/n

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Paul & Virginie - Centriole Lab @centriolelab.bsky.social · 10/12/2025

🥳 Our new paper on C2CD3 is out in @plosbiology.org With the labs of @cellarchlab.com , @chgenoud.bsky.social , and @stearnslab.bsky.social , we revealed the mammalian centriole Distal Ring architecture by combining #UExM and in situ #CryoET. Big congrats to @ebertiaux.bsky.social and all involved.

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Connie Yan @connieyan.bsky.social · 08/12/2025

I'll be sharing my work on how cells know when to make missing structures at #cellbio2025 today! Come check out my poster (B406) and my talk in the Evolutionary Cell Bio mini symposium session which starts at 4pm.

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Wallace Marshall @wallaceucsf.bsky.social · 07/12/2025

The giant ciliate Stentor has a macronucleus that undergoes a dramatic shape change during cellular regeneration. In poster 038 at CellBio2025 Monday Dec 8, I present work by Isabella Ibalio showing that histone modifications correlate with these dramatic nuclear shape changes.

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Wallace Marshall @wallaceucsf.bsky.social · 07/12/2025

Stentor is a single cell that can regenerate missing pieces, but how does it know when something is missing? In poster 406 at CellBio2025 Monday Dec 8, Connie Yan shows that conserved cell cycle machinery plays a key role in triggering cellular regeneration.

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Wallace Marshall @wallaceucsf.bsky.social · 07/12/2025

Stentor is a single cell with a complex cortical pattern showing anterior/posterior polarization In poster 410 at CellBio2025 Monday Dec 8, Yina Hudnall shows a role for posterior-enriched mRNA that encoding DNA binding proteins.

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Wallace Marshall @wallaceucsf.bsky.social · 07/12/2025

Mitochondria form dynamic networks that can be represented as graphs. But the space of graphs is complex. In poster 376 at CellBio2025 Monday Dec 8, Raphie Mostov presents a mathematical approach to represent mitochondria far more simply.

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Wallace Marshall @wallaceucsf.bsky.social · 07/12/2025

The cell is a crowded place where organelles are packed together . In poster B365 at CellBio2025 Monday Dec 8 in the Quantitative Modeling session room 122, Mary Mirvis uses soft x-ray tomography to explore how packing interactions affect organelle shape and interaction.

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Wallace Marshall @wallaceucsf.bsky.social · 07/12/2025

The low Reynolds number of cytoplasmic flow which makes mixing hard. In poster 359 at the CellBio2025 meeting Sunday Dec 7, Ulises Diaz shows how giant cells leverage reversible actin gel assembly to drive rapid mixing of cytoplasm, faster even than "chaotic mixing" schemes.

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Wallace Marshall @wallaceucsf.bsky.social · 07/12/2025

Flagellar length control in Chlamydomonas is a paradigm for organelle size regulation. In poster 163 at CellBio2025 Sunday Dec 7, I present work by Hiro Ishikawa using a synthetic biology approach to test a length-sensing model based on diffusion of kinesin in flagella

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Wallace Marshall @wallaceucsf.bsky.social · 07/12/2025

Flagellar length control in Chlamydomonas is a paradigm for organelle size regulation. In poster 155 at the CellBio2025 meeting Sunday Dec 7, Ximena Garcia Arceo uses Lithium, which increases intraflagellar transport, as a tool to probe how length-altering mutants work.

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Wallace Marshall @wallaceucsf.bsky.social · 05/12/2025

Cells can hunt prey, solve mazes, and learn from past experience. Does this mean they can think, at some level? Find out more at our upcoming session on "Cell Behavior and Cognition" at the ASCB/EMBO #cellbio2025 meeting, Saturday 1-3 pm rm 115.

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Billie Meadowcroft @billiemeadowcroft.bsky.social · 22/10/2025

Your go-to tutorial for simulating mesoscale membranes is here. Look no further for: -Understanding the state of the field -A guide for creating new models for your science -Hands-on tutorials to simulate your very own membranes See tinyurl.com/punk3tcu and the below 🧵 start your journey 💻

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Guillermina Ramirez-SanJuan @guille-rochelle.bsky.social · 18/09/2025

In another exciting development our new preprint is online: www.biorxiv.org/cgi/content/... This is the work of my brilliant graduate student Katerina Kourkoulou in collaboration with Maggie Liu and Arnold Mathijssen. Here is a video of the subject of our study:

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Center for Open Science @cos.io · 12/08/2025

Metascience 2025 recordings are now available! #Metascience25 gathered researchers, funders, policymakers & more to explore how the research process can improve. The program included preconference symposia & plenary sessions on topics from policy change to AI in research. 🎥 cassyni.com/s/metasc...

cassyni.com

Cassyni | Science starts with a seminar

Seamlessly organise, run and publish academic research seminars. Get started in minutes.

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EMBL Events @events.embl.org · 31/07/2025

📢 Abstract submission deadline reminder for 'Cell biology of the nucleus'! Before packing your bags and leaving for your summer vacation, there is one important task left to do: submit your abstract for #EESNucleus ✍️ Deadline is 26 August: s.embl.org/ees25-07-bl

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Mary Mirvis @marymirvis.bsky.social · 06/05/2025

So excited to be in Heidelberg for www.embl.org/about/info/c... ! This is going to be an awesome meeting, been looking forward to it for months! #EESTCBio

embl.org

Theory and concepts in biology

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Danielle Grotjahn @nanigrotjahn.bsky.social · 01/05/2025

🚨New preprint!🚨 #teamtomo We expanded Surface Morphometrics to quantify membrane thickness from cryo-ET—revealing local variation across organelles. Led by the lab’s first grad student, @mmedina300kv.bsky.social (defending Monday! 🍾) w/ @attychang.bsky.social @hamid13r.bsky.social & @tomo.science

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Mary Mirvis @marymirvis.bsky.social · 29/04/2025

I’ll be there! Can’t wait!

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Mary Mirvis @marymirvis.bsky.social · 29/04/2025

Thanks! I think it’s just edge detection & 3D project plus a little B&C adjustment in FIJI 🙂

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Mary Mirvis @marymirvis.bsky.social · 28/04/2025

I agree, lately I increasingly prefer to frame gaps in knowledge as questions rather than these types of “little is known/poorly understood” statements, which are inherently vague and subjective. Questions are more engaging to a reader too imo