Ashutosh Kumar

Meet Hofund, the N-terminal amphipathic helix of 15 aa in Heimdall ESCRT-IIIA (named after Heimdall’s sword).
How do we know Hofund is the molecular trigger for fission?
Remove Hofund → ESCRT-IIIA loses fission activity.
Add Hofund alone → uncontrolled fission.

Molecular basis for cellular compartmentalization by an ancient membrane fission mechanism The emergence of cell compartmentalization depends on membrane fission to create the endomembrane compartments. In eukaryotes, membrane fission is commonly executed by ESCRT-III, a protein complex con...

New preprint from the lab!!🎉
We show that Asgard archaea ESCRT-III proteins can trigger membrane fission and reveal its molecular mechanism, offering clues to how these cells may have built internal compartments. But do these organisms even have these compartments?
www.biorxiv.org/content/10.1...

Thanks to @snsf.ch, we are hiring two PhD students to investigate frontier topics in lipid biology using a combination of MD simulations and experiments. Preferred starting date: ASAP. Fribourg - and Switzerland - are quite nice, for both work and private life! Please spread the word!

Happy to share the latest from the lab, led by Daniel Alvarez, in collaboration with @lizconibear.bsky.social‬. In this AA-MD tour-de-force, we delve deep into the mechanism and energetics of lipid uptake by bridge-like lipid transfer proteins, and we learn a few interesting things along the way...

1 month to abstract deadline for the first cell biology of the nucleus meeting at @embl.org in many years - organised by the stellar @luskinglab.bsky.social @sarawickstrom.bsky.social Tom Quail & Simone Koehler

Tons of open slots, invited and selected speakers all get 20 mins ❤️

#EESNucleus

Altogether, we think that the mechanism of membrane fusion described in the context of NPC assembly here is different from what known for other fusion machineries (e.g. SNAREs, dynamin-like GTPases,…). More details in the manuscript—let us know your thoughts! (13/13)

When observed closely, lipid mixing looks like classic hemifusion-like intermediates with exposed lipid-tails (but stabilized within protein rings here). (10/13)

Happy to share the latest work from the lab, led by @mudgal17.bsky.social‬, in collaboration with the Weis lab @ethzurich.bsky.social.
How do nuclear membranes fuse during NPC assembly? We answer this question in our latest work, where we identify a new mechanism for membrane fusion… (1/13)

Unexpectedly, @jurgjn.bsky.social found that running Alphafold3 predictions for protein interactions can yield ipTM scores that are more predictive of true interactions when run in pools of proteins instead of pairwise predictions. Presumably, this reflects some sort of "competition effect".

Our lab is hiring 1 PhD and 1 Postdoc to study the mechanism of lipid transport using computational methods (Molecular Dynamics, AI). Fully funded by @snsf-ch.bsky.social for 4 years, with amazing collaborators and excellent life and working conditions. Apply by email. Please share and repost!

RNA Order Regulates Its Interactions with Zwitterionic Lipid Bilayers RNA–lipid interactions directly influence RNA activity, which plays a crucial role in the development of new applications in medicine and biotechnology. However, while specific preferential behaviors ...

Talented postdoc Akhil Singh (with help from recent graduate Janak Prabhu) provided a thorough investigation of RNA-membrane interactions using AA simulations, finding that RNA order regulates its interactions with zwitterionic bilayers (1/2)
pubs.acs.org/doi/full/10....

An S-acylated N-terminus and a conserved loop regulate the activity of the ABHD17 deacylase ABHD17 enzymes remove fatty acids from membrane proteins like NRas. This study shows that their activity depends on two mobile regions: an S-acylated N-ter

The work of “soon-to-be” (we will miss her!) graduate Jennifer Sapia on the S-acylase ABHD17 (in collaboration with the lab of @lizconibear.bsky.social and grad student Sydney Holme) is also out! (1/3)
buff.ly/4b3E0xy

Star PhD student Cristian Rocha Roa, in collaboration with Jieqiong Gao and the Ungermann lab, identified endosomal protein Any1 in yeast, and SLC66A2 in human, as novel lipid scramblases. (1/2)
rupress.org/jcb/article/...

Pex30-dependent membrane contacts sites maintain ER lipid homeostasis In eukaryotic cells, communication between organelles and the coordination of their activities depend on membrane contact sites (MCS). How MCS are regulated under the dynamic cellular environment rema...

While, in a nice collaboration with the Carvalho lab and @joanavferreira.bsky.social, PhD student Yara Ahmed used MD simulations to characterize the binding mechanism of the Dysferlin domain of Pex30 to phosphatidic acid. Anyone interested in a novel PA-sensor? (2/2)
www.biorxiv.org/content/10.1...

Amphipathic helices sense the inner nuclear membrane environment through lipid packing defects Amphipathic helices (AHs) are ubiquitous protein motifs that modulate targeting to organellar membranes by sensing differences in bulk membrane properties. However, the adaptation between membrane-tar...

Finally, a couple of nice preprints from younger members of the lab. Pre-doc Mira Mors (now PhD student in Stuttgart) contributed to this thorough screening of amphipathic helices by @shoken-lee.bsky.social from the @bahmanyarlab.bsky.social lab! (1/2)
www.biorxiv.org/content/10.1...

Amino Acid Transfer Free Energies Reveal Thermodynamic Driving Forces in Biomolecular Condensate Formation https://www.biorxiv.org/content/10.1101/2024.12.01.625774v1 The self-assembly of intrinsically disordered proteins into biomolecular condensates shows a depende

Amino Acid Transfer Free Energies Reveal Thermodynamic Driving Forces in Biomolecular Condensate Formation https://www.biorxiv.org/content/10.1101/2024.12.01.625774v1

Meet the CALVADOS RNA model

Ikki Yasuda, Sören von Bülow & Giulio Tesei have parameterized a simple model for disordered RNA. Despite it's simplicity (no sequence, no base pairing) we find that it captures several phenomena that depend on the charge, stickiness and polymer properties of RNA 🧬🧶🧪

Stereochemistry in the disorder–order continuum of protein interactions - Nature Studies on protein–protein interactions using proteins containing d- or l-amino acids show that stereoselectivity of binding varies with the degree of disorder within the complex.

We did this crazy project where we tried to see if proteins could interact with their mirror image ligand. Seems impossible when proteins need to form 3D structures to interact. But what about if the interaction remains disordered???

www.nature.com/articles/s41...

Would like to be added here✋. Thanks :)

📌

An Intermediate Resolution Model of RNA Dynamics and Phase Separation with Explicit Mg2+ https://www.biorxiv.org/content/10.1101/2024.11.17.624048v1 RNAs are major drivers of phase separation in the formation of biomolecular condensates. They can al

An Intermediate Resolution Model of RNA Dynamics and Phase Separation with Explicit Mg2+ https://www.biorxiv.org/content/10.1101/2024.11.17.624048v1

Identifying Sequence Effects on Chain Dimensions of Disordered Proteins by Integrating Experiments and Simulations It has become increasingly evident that the conformational distributions of intrinsically disordered proteins or regions are strongly dependent on their amino acid compositions and sequence. To facili...

New collaborative work in collaboration with the labs of Robert Best & Tanja Mittag driven by Ben Schuler.
Identifying Sequence Effects on Chain Dimensions of Disordered Proteins by Integrating Experiments and Simulations.
pubs.acs.org/doi/10.1021/...

Postdoctoral fellow - Uppsala (Stad) (SE) job with Uppsala University, Department of Chemistry - BMC | 12832275 The laboratory of Prof. Ylva Ivarsson is seeking a highly motived candidate for a two-year postdoctoral fellowship on a project focused on short li...

We have a 2-year #postdoc position in my lab supported by a fellowship from the Carl Trygger foundation. Intrinsically disordered regions, modular domains, protein-protein interactions, phage display and more. More info here: www.nature.com/naturecareer...

Hello Bluesky! We're thrilled to announce an open PhD position on exploring controlling condensate membrane attachment and exocytosis! Collaborate across Europe in the ComeInCell EU network. Apply now! Details: www.comeincell.org & www.ru.nl/en/working-a...

Thrilled to announce Boltz-1, the first open-source and commercially available model to achieve AlphaFold3-level accuracy on biomolecular structure prediction! An exciting collaboration with Jeremy, Saro, and an amazing team at MIT and Genesis Therapeutics. A thread!

The potential energy surface for diatomic Cr-Cr mapped out using seven universal machine learning force fields. They are bumpier than one would expect.

You try a "universal" machine learning force field and wonder why the wheels start falling off your simulations. A scroll through "homonuclear diatomics" on huggingface.co/spaces/atomi... is informative! #CompChem #CompChemSky

Even though Newton's laws are deterministic, the behavior of many interacting bodies is so chaotic that it looks essentially "random."

Statistical mechanics effectively says: why bother with all those complex trajectories? Just go ahead and replace them with truly random motion.

Could you please add me too?

Disentangling folding from energetic traps in simulations of disordered proteins Protein conformational heterogeneity plays an essential role in a myriad of different biological processes. Extensive conformational heterogeneity is especially characteristic of intrinsically disorde...

I’m excited to share my most recent manuscript describing an approach to assess local conformational sampling in simulations of intrinsically disordered proteins. This one’s for my computational biophysics aficionados www.biorxiv.org/content/10.1... a 🧵

I would like to be added here, if possible please. Thanks :)