Reposted by Taylor MighellAtlas of Variant Effects Alliance @varianteffect.bsky.social · 01/12/2025Tomorrow! www.varianteffect.org/seminar-seri... 054
Reposted by Taylor MighellJingyou Rao @jingyour.bsky.social · 04/11/2025🎙️ Next up Dec 2 in VESS! Thea Schulze (Lindorff-Larsen Lab): Predicting mutated protein abundance @tkschulze.bsky.social Taylor Mighell (Lehner Lab): Massive mutagenesis to understand GPCRs @taylor-mighell.bsky.social 🔗 More info at varianteffect.org/seminar-series @varianteffect.bsky.social 054
Reposted by Taylor MighellNature Structural & Molecular Biology @natsmb.nature.com · 22/09/2025New online: A small molecule stabilizer rescues the surface expression of nearly all missense variants in a GPCRgo.nature.comA small molecule stabilizer rescues the surface expression of nearly all missense variants in a GPCRNature Structural & Molecular Biology, Published online: 22 September 2025; doi:10.1038/s41594-025-01659-6Many mutations cause disease because they destabilize proteins. Here, Mighell and Lehner show that a single small molecule can correct the destabilization caused by nearly all pathogenic mutations in a human GPCR. 053
Taylor Mighell @taylor-mighell.bsky.social · 01/06/2025GPCR-MAPS is now live! www.biorxiv.org/content/10.1... A new platform for high resolution functional mapping of GPCRs with massive mutagenesis. We identify the core activation network, residues involved in biased signaling, and generate >7,000 full dose response curves. With @benlehner.bsky.socialbiorxiv.orgThe genetic architecture of G-protein coupled receptor signalingG-protein coupled receptors (GPCRs) are the most abundant class of human receptors and drug targets. The vast majority of GPCR drugs bind the conserved orthosteric pocket, which can lead to non-specif... 1154
Reposted by Taylor MighellbioRxiv SysBio @biorxiv-sysbio.bsky.social · 31/05/2025The genetic architecture of G-protein coupled receptor signaling www.biorxiv.org/content/10.1101/202… 084
Reposted by Taylor MighellJonathan Frazer @jonnyfrazer.bsky.social · 23/05/2025Another local hero! Up next at #VariantEffect25: @taylor-mighell.bsky.social from @benlehner.bsky.social lab presents: Two wrongs make a right: can GPCR antagonists rescue mutant receptors? 🧬🧪🔁 062
Reposted by Taylor MighellIsabelle Zane @isabellease.bsky.social · 23/05/2025@taylor-mighell.bsky.social at #VariantEffect25 083
Reposted by Taylor MighellCentre de Regulació Genòmica (CRG) @crg.eu · 08/01/2025Introducing Human Domainome v1, the largest and most comprehensive library of human protein variants to date, which maps the effects of +500K mutations across 522 domains. The study by @benlehner.bsky.social and Toni Beltran is out now in @nature.com. Illustration by @queralttolosa.bsky.social. 13411
Reposted by Taylor MighellBen Lehner @benlehner.bsky.social · 19/01/2025Nice highlighting of @taylor-mighell.bsky.social's GPCR pharmacochaperone preprint by @dereklowe.bsky.social @science.org www.biorxiv.org/content/10.1...biorxiv.orgA pharmacological chaperone stabilizer rescues the expression of the vast majority of pathogenic variants in a G protein-coupled receptorReduced protein stability is the most frequent mechanism by which rare missense variants cause disease. A promising therapeutic avenue for treating destabilizing variants is pharmacological chaperones... 0114
Reposted by Taylor MighellCentre de Regulació Genòmica (CRG) @crg.eu · 09/01/2025Missense mutations are responsible for many heritable genetic disorders. Researchers led by @benlehner.bsky.social are carrying out large-scale experiments to understand why. Unstable proteins are emerging as a clear mechanism of action. Today in @elpais.com by @manuelansede.bsky.social.english.elpais.comThe first ‘human domainome’ reveals the cause of a multitude of diseasesAn ingenious large-scale experiment in Barcelona has led to the creation of a catalog detailing the effects of half a million DNA mutations 0244
