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Krishna Shrinivas @shrinivaslab.bsky.social · 2h

Our framework:

We bridge machine learning & statistical physics to directly invert molecular simulations to design IDPS and engineer examples that:

🌀 form loops & linkers with tuned flexibility
⚡ sense salt, temperature, or phosphorylation stimuli
🤝 bind disordered targets like FUS or Whi3

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Krishna Shrinivas @shrinivaslab.bsky.social · 2h

The problem:
AI tools like AlphaFold & ProteinMPNN accelerate design of stable protein folds by inverting the sequence-structure map.

But IDPs don't have 1 shape - they occupy a huge ensemble of shapes. Physics simulations are good models to generate ensembles but hard to design/invert over!

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Krishna Shrinivas @shrinivaslab.bsky.social · 2h

Happy to share our latest in @natcomputsci.nature.com
led by (amazing) Ryan Krueger + colab w M. Brenner!

We introduce a framework to directly design intrinsically disordered proteins (IDPs) from physics-based simulations.
🧬 doi.org/10.1038/s435...
📰 www.mccormick.northwestern.edu/news/article...

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Reposted by Krishna Shrinivas

Kalki Kukreja @kkukreja.bsky.social · 1d

Our review on cell cycle – cell fate (de)coupling is out! doi.org/10.1242/dev....
Was a lot of fun writing this with Allon Klein, reading old papers(earliest from 1902), and speculating on why cell cycle progression is not necessary for differentiation across many many tissues and species.
(1/3)

Coupling and decoupling of the cell cycle from cell differentiation in development

Summary: This Spotlight surveys investigations of the dependence of cellular differentiation on the cell cycle in animals. Strict dependence is uncommon. The decoupling of the cell cycle and different...

doi.org

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Reposted by Krishna Shrinivas

Nature Computational Science @natcomputsci.nature.com · 3d

📢 @shrinivaslab.bsky.social and colleagues introduce a method for designing unstructured proteins with tunable properties. www.nature.com/articles/s43... 🖥️ 🧬

🔓 rdcu.be/eJSuV

Generalized design of sequence–ensemble–function relationships for intrinsically disordered proteins - Nature Computational Science

The authors introduce a method that combines physics and machine learning to design dynamic unstructured proteins with tunable ensemble properties like size, shape, sensing and binding.

www.nature.com

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Reposted by Krishna Shrinivas

Kresten Lindorff-Larsen @lindorfflarsen.bsky.social · 3d

A good day to remember John Gurdon’s school report from his biology master at Eton

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Krishna Shrinivas @shrinivaslab.bsky.social · 7d

Many congrats Alex! Your labs research has been a pleasure to read (and try code openly). Hope you are celebrating 🍾

Reposted by Krishna Shrinivas

Krishna Shrinivas @shrinivaslab.bsky.social · 17d

Preprint!

Inspired by condensates that form on specific DNA, we ask:

can we design multicomponent fluids to form distinct condensates on diff. surfaces?

i.e. perform classification by condensation ⚛️ 💻 exploiting phase transitions beyond compartmentalization!
arxiv.org/abs/2509.08100
(1/2)

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Krishna Shrinivas @shrinivaslab.bsky.social · 17d

Led by the amazing Aidan Zentner, with contribs from Ethan Halingstad, and in collab with Cameron Chalk, Michael Brenner, @amurugan.bsky.social, and Erik Winfree.

For a more fun overview, see Erik's version of the abstract www.dna.caltech.edu/DNAresearch_... :) (2/2)

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Krishna Shrinivas @shrinivaslab.bsky.social · 17d

Preprint!

Inspired by condensates that form on specific DNA, we ask:

can we design multicomponent fluids to form distinct condensates on diff. surfaces?

i.e. perform classification by condensation ⚛️ 💻 exploiting phase transitions beyond compartmentalization!
arxiv.org/abs/2509.08100
(1/2)

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Reposted by Krishna Shrinivas

brangwynnelab.bsky.social @brangwynnelab.bsky.social · 20d

A tremendous honor! Thrilled & humbled to receive 2025 Keio Medical Science Prize for launching LLPS #phaseseparation field (= #softmatter + #cellbio) w collaborators esp @HymanLab. & Congrats to Akiko Iwasaki @virusesimmunity.bsky.social. www.princeton.edu/news/2025/09...
#KeioMedicalSciencePrize

Bioengineer Clifford Brangwynne wins Keio Medical Science Prize

Japan’s Keio University awards the prize annually to honor contributions in medicine and life sciences. Brangwynne is being recognized for groundbreaking work that has opened up a new field of cell bi...

www.princeton.edu

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Krishna Shrinivas @shrinivaslab.bsky.social · 27d

congrats Amy!

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Krishna Shrinivas @shrinivaslab.bsky.social · 28d

Our work highlighted in @science.org by L. Bryan Ray!

www.science.org/doi/10.1126/...

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Krishna Shrinivas @shrinivaslab.bsky.social · Sep 4

This project began at the @mblscience.bsky.social Physiology course 🌊 and grew into a FUN collaboration over many years across Northwestern and Duke - thanks all for the support and more coverage below!

📰 Coverage:
www.mccormick.northwestern.edu/news/article...

www.mbl.edu/news/physiol...

Cell Feature Implicated in Cancer Forms Differently than Previously Thought

A team with Professor Krishna Shrinivas discovered how a landmark found in the nucleus of cells in many organ systems forms through a different mechanism than the well-established view, a revelation t...

www.mccormick.northwestern.edu

Krishna Shrinivas @shrinivaslab.bsky.social · Sep 4

Extra curiosities 🔍
•⁠ ⁠Across tissues & species, stoichiometries of NONO/FUS are conserved, hinting at evolutionary tuning.
•⁠ ⁠Simulations by Mary Skillicorn in the lab also suggest important roles for co-transcriptional nucleation of paraspeckles for tuning paraspeckle size/number.

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Krishna Shrinivas @shrinivaslab.bsky.social · Sep 4

Another surprise: core & shell proteins don’t mix well (they’re immiscible, like oil & water).

Putting these observations together in simulations suggests 🖥️⚛️: competition for RNA + immiscibility naturally push proteins to form different layers, even if they individually like the same parts of RNA.

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Krishna Shrinivas @shrinivaslab.bsky.social · Sep 4

We combined in vitro assays of binding and condensation with bioinformatics to ask which parts of NEAT1 each protein preferred binding to.

Surprise: core proteins (FUS, NONO) actually prefer the same shell RNA regions as the shell protein TDP-43! Everyone crowds into the same RNA zones. 🌀

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Krishna Shrinivas @shrinivaslab.bsky.social · Sep 4

Prevailing model suggests:

→ “Core” proteins bind the middle of the NEAT1 RNA scaffold
→ “Shell” proteins bind the RNA ends

This selective binding could, in principle, assemble layers - but has not been explicitly tested. So we set out to do this!

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Krishna Shrinivas @shrinivaslab.bsky.social · Sep 4

We use paraspeckles as a model to study this question.

Paraspeckles are built around a non-coding RNA NEAT1 whose middle regions are in the core and 5’/3’ ends on the shell layer - each layer also recruiting different proteins. (2/6)

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Krishna Shrinivas @shrinivaslab.bsky.social · Sep 4

New in @pnas.org with @gladfelterlab.bsky.social @sneadlab.bsky.social ! 📢

Cells use condensates (dynamic compartments without membranes) to organize key reactions. Some condensates have core & shell layers… but how do such layers form? 🤔

👉 pnas.org/doi/10.1073/pnas.2504778122 (1/6)

PNAS

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans...

pnas.org

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Reposted by Krishna Shrinivas

Gladfelter Lab @gladfelterlab.bsky.social · Aug 7

Our paper on the spatial organization of nuclear paraspeckles is out in #PNAS! Excited to see what comes next from the teams of @shrinivaslab.bsky.social and @sneadlab.bsky.social at Northwestern! pnas.org/doi/10.1073/pnas.2504778122

PNAS

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans...

pnas.org

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Reposted by Krishna Shrinivas

Alexis Verger 🧬🧫🧪 @alexis-verger.cpesr.fr · Jul 18

The Baker lab @uwproteindesign.bsky.social apparently had a lot of fun 😂

some examples of sequences used in the paper www.science.org/doi/10.1126/...

DAVIDLIKESPEPTIDE
DAVIDITISTIME
DANIELSILVA
HIALIENFRIEND

Design of intrinsically disordered region binding proteins

Intrinsically disordered proteins and peptides play key roles in biology, but a lack of defined structures and high variability in sequence and conformational preferences have made targeting such syst...

www.science.org

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Krishna Shrinivas @shrinivaslab.bsky.social · Jul 1

Super interesting!

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Reposted by Krishna Shrinivas

Dave Shechner @shechnerlab.bsky.social · Jun 30

Hello! Ever wonder what's "talking to" your favorite transcript, but were too scared to ask? In our review in @cp-cellreports.bsky.social, @mardakheh.bsky.social and I highlight new RNA-focused tools for discovering RNA interactions across organizational scales. Checkit!

tinyurl.com/ydn6e3ac

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Krishna Shrinivas @shrinivaslab.bsky.social · Jun 24

Congrats @deeparajan.bsky.social!

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