Iva Tolić

Cell enlargement causes mitotic errors and aneuploidy in cells that evade senescence after CDK4/6 inhibition CDK4/6 inhibitors (CDK4/6i) arrest the cell cycle in G1 leading to cellular overgrowth and p53-dependent senescence. They are used to treat metastatic HR+/HER2- breast cancer, but resistance is common...

Delighted to share our latest work showing how cells that evade #senescence after CDK4/6 inhibition are primed to become aneuploid because of their increased size (due to defects in cohesion and the mitotic checkpoint). Great work by fab PhD student Aanchal Pareri 👏🧪

www.biorxiv.org/content/10.1...

Amazing energy at our second Swiss-Croatian Bilateral Project meeting with @labmeraldi.bsky.social and Pavin Group in Srebreno near Dubrovnik! The labs teamed up instantly, with lots of brainstorming and cool ideas for new joint projects! #HRZZ @snsf-ch.bsky.social
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Great memories from the joint meeting with the Meraldi Lab and Pavin Group last year in Split! Can't wait for this year's meeting, which starts tomorrow! Excited for more cool science through our Swiss-Croatian Bilateral Project #HRZZ @snsf-ch.bsky.social 🇭🇷🇨🇭

Perfect for PhD students and postdocs! www.atoutcom.com/shaping-life...

Happy first day of spring from our Institute @institutrb.bsky.social!

Join us for this small, intensive workshop in the remote Alpine town of Arolla, where we will explore the dynamics of living systems across scales, from the cytoskeleton to embryos. Let’s dive into how cellular and tissue-scale dynamics shape life itself! meetings.ls2.ch/arolla2025

Introducing blebbisomes! Cover art by @ento-sanchez.bsky.social! #CellBiology
Article: www.nature.com/articles/s41...

🎉 Congrats to @lgudlin.bsky.social, @krunovuk.bsky.social, and Maja Novak for the awesome work! This was a super fun collaboration with Nenad Pavin, including our ERC Synergy team @erc.europa.eu - @kopslab.bsky.social and MIT. Special thanks to Zuzana Storchova, Josip Tambača, and Matko Ljulj! 🚀

🌱🦎 And the coolest outlook? This spindle adaptability may enable polyploid cell proliferation, explaining how plants, fish, amphibians, and reptiles manage polyploidy! Since many cancers are polyploid/aneuploid, this adaptability could be key to their spread, and a hidden vulnerability.

The chromosome crowding model also explains why cells round up during mitosis and why species with bigger genomes undergo open mitosis — it gives more room for the spindle, helping to avoid excessive pushing forces between chromosomes.

Here’s the gist: When the DNA length increases by a factor of n, the width of the metaphase plate increases by only the cube root of n. So, large genomes require small spindle adjustments. This gives us a predictive framework for how spindles adapt to different genome sizes.

🌍 And now the crazy part: The scaling law predicted by our model matches experimental data across eukaryotic species, from yeast to plants and animals! This means that chromosome crowding is a universal principle of spindle scaling.

To explain this, we built a new theoretical model, where each chromosome is squeezed by the pushing forces from the neighbors. This pushes the microtubule outward, balanced by forces anchoring its ends at the poles. We validated the model by mechanical manipulations of cells.

We put this to the test by changing chromosome numbers and mechanics in healthy and cancer cells, plus using natural variations in chromosome numbers in colon cancer organoids and primary mouse cells. The results? Strong evidence for chromosome crowding as a key player!

So far, spindle size was thought to be controlled mainly by microtubules, motor proteins, and centrosomes. We flipped the script and hypothesized that chromosome crowding forces play a crucial role in shaping the spindle.

💡 But guess what? We found a scaling law in which the metaphase plate scales with genome size, following a power law with an exponent of about 1/3.

🔬 Spindles come in all shapes and sizes, and the genomes they need to divide vary by four orders of magnitude across eukaryotes. So it wasn’t clear if a single scaling law could explain how the spindles handle such drastically different genome sizes.

🚀Ever wondered if there's a universal rule of spindle scaling across eukaryotes? Turns out, there is! Our study reveals an evolutionarily conserved principle driven by a surprising factor: chromosome crowding. 🧵👇
shorturl.at/MmPNr

Happy Women’s Day to all the amazing women out there! Special congrats to two incredible young scientists from my lab, Valentina Štimac & Isabella Koprivec, who earned their PhDs last year! 💡 And a spotlight on Valentina for winning the L'Oréal-UNESCO For Women in Science award! 🔥 #WomeninSTEM