Bryan Roth

North Carolina

Insights Director at Sightlines

@feelgoodscomp analyst. @sightlines_news insights. @peterfrost: "A bright, shining light in an otherwise empty world." @andwoo: “Never meet your heroes.”

Articles

Orchestrating NTSR1 signaling from the interface - Cell Research

3 weeks ago | nature.com | Brian Krumm |Bryan Roth

You have full access to this article via your institution. Biased allosteric modulators provide great therapeutic potential by selectively directing signal bias in the presence of endogenous ligand under (patho)physiological conditions. In a recent Cell Research paper, Sun et al. revealed the structural mechanisms underlying the biased allosteric modulation exerted by SBI-533 directly at the neurotensin receptor 1–β-arrestin1 interface.
Chemogenetics for sensing antigens - Cell Research

Jan 14, 2025 | nature.com | Bryan Roth

Antigen-based systems offer highly specific binding and customizability, broadening their application to various fields of cell biology. In a recent issue of Nature, Kalogriopoulos et al. design antigen-sensing G-protein-coupled receptors that exhibit programmable responses spanning exogenous gene expression, G-protein signaling, and receptor activation. The desire to control cellular responses has long been an active area of research.
Get Niche or Die Trying — Sightlines

Oct 28, 2024 | sightlines.news | Bryan Roth

Listen on Spotify, Apple, or anywhere you find your podcasts. You can also watch on YouTube for additional visual insights. Giving context to top news from across alcohol through the reporting and research we've conducted at Sightlines. Subscribe to get these insights in your inbox. 1. Better understanding the THC consumerSightlines insights have showcased how people who use cannabis also drink alcohol and what that could mean for sales of some categories.
A neurodevelopmental disorder mutation locks G proteins in the transitory pre-activated state - Nature Communications

Aug 4, 2024 | nature.com | Kevin Knight |Brian Krumm |W. Grant Ludlam |Meng Cui |Tyler J. Lefevre |Wenyuan Wei | +9 more

AbstractMany neurotransmitter receptors activate G proteins through exchange of GDP for GTP. The intermediate nucleotide-free state has eluded characterization, due largely to its inherent instability. Here we characterize a G protein variant associated with a rare neurological disorder in humans. GαoK46E has a charge reversal that clashes with the phosphate groups of GDP and GTP.
Piecing together aminergic polypharmacology - Cell Research

May 12, 2024 | nature.com | Bryan Roth

Neuropsychiatric medications are often designed to have affinity for multiple ligand-binding sites across different receptor types to increase therapeutic efficacy. In a recent paper in Cell, Chen and colleagues implement a flexible scaffold-based cheminformatics approach to design bi-target therapeutics for dementia-related psychosis.
Entendiendo los psicodélicos en el SNC

Mar 19, 2024 | psiquiatria.com | Bryan Roth |Blake A Fordyce

Durante siglos, linajes antiguos han consumido compuestos psicodélicos de fuentes naturales. Desde entonces, en la era moderna, los científicos han aprovechado el poder de las herramientas computacionales, los ensayos celulares y las métricas de comportamiento para estudiar cómo estos compuestos provocan cambios a nivel molecular, celular, de circuito y de sistema. Aqu... Durante siglos, linajes antiguos han consumido compuestos psicodélicos de fuentes naturales.
Author Correction: PRESTO-Tango as an open-source resource for interrogation of the druggable human GPCRome - Nature Structural & Molecular Biology

Mar 14, 2024 | nature.com | Bryan Roth

Correction to: Nature Structural & Molecular Biology https://doi.org/10.1038/nsmb.3014. Published online 20 April 2015. Following publication of this article, the University of North Carolina website hosting the sequences of all of the receptor inserts produced in the study has become defunct; data are now accessible at https://pdsp.unc.edu/prestotango/. About this articleKroeze, W.K., Sassano, M.F., Huang, XP. et al.
Alternative splicing of latrophilin-3 controls synapse formation - Nature

Jan 17, 2024 | nature.com | Shuai Wang |Wenfei Sun |Stephen R. Quake |Bryan Roth

AbstractThe assembly and specification of synapses in the brain is incompletely understood1,2,3. Latrophilin-3 (encoded by Adgrl3, also known as Lphn3)—a postsynaptic adhesion G-protein-coupled receptor—mediates synapse formation in the hippocampus4 but the mechanisms involved remain unclear. Here we show in mice that LPHN3 organizes synapses through a convergent dual-pathway mechanism: activation of Gαs signalling and recruitment of phase-separated postsynaptic protein scaffolds.
Examining psychedelic drug action - Nature Chemistry

Jan 4, 2024 | nature.com | Bryan Roth

Dewran Kocak and Bryan Roth discuss a psychedelic — 5-MeO-DMT — and what we might learn from its properties. It was in 2016 when several small-scale clinical studies using psilocybin — the active ingredient in ‘magic’ mushrooms — reported promising results. Phase II trials have now shown that one administration of psilocybin can produce statistically significant clinical effects for depression and anxiety1,2.
Docking for EP4R antagonists active against inflammatory pain - Nature Communications

Dec 6, 2023 | nature.com | Stefan Gahbauer |Joao M. Braz |Hye Jin Kang |Christian B. Billesbølle |Yongfeng Liu |Tao Che | +7 more

AbstractThe lipid prostaglandin E2 (PGE2) mediates inflammatory pain by activating G protein-coupled receptors, including the prostaglandin E2 receptor 4 (EP4R). Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce nociception by inhibiting prostaglandin synthesis, however, the disruption of upstream prostanoid biosynthesis can lead to pleiotropic effects including gastrointestinal bleeding and cardiac complications.