Fantastic new preprint from @lesloew!!.

RT @lesloew: Check our our new preprint. Combining measured solution rate constants and structural data to estimate bimolecular rate consta….

Together our results allowed us to develop a novel model for how shank2 controls RNA translation. We propose that mutations in shank2, like those in our study, result in dysregulated condensate physical properties, composition, and function to cause observed disease phenotypes.

In neurons with one copy of wild-type SHANK2 and a truncated SHANK2, we show that FMRP is mislocalized away from shank2 condensates, the ratio of phospho-FMRP to FMRP is increased, and expression of FMRP-targeted CaMKII is decreased, as predicted by our model.

In human neurons, we found similar observed phenotypes; FMRP was well-localized with wild-type shank2 but overexpression of either shank2 mutant in a wild-type shank2 background resulted in mislocalization of FMRP away from shank2 condensates.

We found that phosphorylation of shank2 mutants also resulted in a significant increase in RNA translation in vitro. These in vitro results allowed us to build a testable model in which shank2 condensates regulate FMRP-targeted translation by controlling FMRP localization.

However, upon phosphorylation of either shank2 mutant, FMRP was enriched at the edges of condensates. Rheometry showed that either mutant increased the elasticity of shank2-containing condensates.

Surprisingly, mutations located roughly 800 residues apart in the shank2 IDR resulted in similar molecular phenotypes even though the saturation concentration for phase separation and dynamics within condensates did not appear to be altered.

Preprint alert from the @Jonathon_Ditlev Lab! In this study led by postdoctoral fellow Leshani Liyanage, we discovered that missense mutations in the IDR of shank2 results in increased condensate elasticity and altered composition and function.

RT @SickKidsNews: #SKResearch from @Jonathon_Ditlev is helping scientists predict phase separations in complex cellular systems. Understan….

RT @AniChattaraj: In this article, we compare simulations and in-vitro experiments to show that Solubility product is a good proxy to ident….

In this study in MBoC, @AniChattaraj and Zeynep Baltaci spearhead our efforts (w/ @lesloew & Bruce Mayer) to develop methods to quantitatively understand and predict phase separation of multivalent binding partners using computational modeling and precise quantitative microscopy.

Led by @yimeiwan together with Jordyn Smith, Rhea Hudson, and Julie Forman-Kay, we investigate the biophysical mechanism for CFTR cluster formation on membranes. We find that clusters of CFTR are consistent with phase separated condensates.

RT @brangwynnelab: Congrats to former postdoc Felix Keber from our & @MartinWuhr lab on this fascinating paper using filtration experiment….

RT @shammas_sarah: Hi everyone. We were made aware that many people were unable to book tickets yesterday. BPS have fixed the issue and ext….

This will be an excellent symposium! Thank you @stromgaardlab for organizing it and for the invitation to share our work!.

Today is the deadline to sign up for the IDP subgroup dinner!.

RT @SamratLabMohali: IDP subgroup program co-chairs Jonathon Ditlev (University of Toronto) @Jonathon_Ditlev & Wade Zeno (University of Sou….

A little late to the party, but here's a link to a new story from our groups about using the solubility product for investigating heterotypic condensation! It has been a pleasure to work with @lesloew @AniChattaraj Bruce Mayer and exceptional student Zeynep Baltaci from my group.

RT @CoachJayArnold: If I’ve said it once I’ve said it a thousand times - I’d set the cuisine of these three states up against anywhere in t….