Taylor Mighell
@taylor-mighell.bsky.social
Postdoc @crg.eu Barcelona GPCRs | synthetic biology | genomics
🎙️ 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
New online: A small molecule stabilizer rescues the surface expression of nearly all missense variants in a GPCR
A small molecule stabilizer rescues the surface expression of nearly all missense variants in a GPCR
Nature 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.
go.nature.com
GPCR-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.social
The genetic architecture of G-protein coupled receptor signaling
G-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...
biorxiv.org
The genetic architecture of G-protein coupled receptor signaling https://www.biorxiv.org/content/10.1101/2025.05.30.656974v1
Another 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? 🧬🧪🔁
Introducing 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.
Nice highlighting of @taylor-mighell.bsky.social's GPCR pharmacochaperone preprint by @dereklowe.bsky.social @science.org www.biorxiv.org/content/10.1...
A pharmacological chaperone stabilizer rescues the expression of the vast majority of pathogenic variants in a G protein-coupled receptor
Reduced 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...
biorxiv.org
Derek Lowe@dereklowe.bsky.social · 2y agoSmall-molecule protein chaperones may have more wide-ranging activity than we thought, and that's good news:
Missense 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.
The first ‘human domainome’ reveals the cause of a multitude of diseases
An ingenious large-scale experiment in Barcelona has led to the creation of a catalog detailing the effects of half a million DNA mutations
english.elpais.com