BryanRoth
@zenbrainest
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James Black: 'the prismatic qualities of the assay distort our view in obscure ways and degrees'
Joined November 2013
Congrats to the team: especially @gori7873 and Brian Krumm from @RothLabUNC and Adrien and Matan from Greg Scherrer's lab!!.A ton of work!.Structure-guided design of a peripherally restricted chemogenetic system: Cell
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PSYCHEDELIC!!!.At long last--30 years of work-finally!.Structure of a Hallucinogen-Activated Gq-Coupled 5-HT2A Serotonin Receptor
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BREAKING NEWS: SCHIZOPHRENIA IS A DISEASE OF THE SYNAPSE!!.
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Finally--structures of D1, D2, D3, D4 and D5-dopamine receptors!!.Congrats to folks from @RothLabUNC , Eric Xu's lab and many others.
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WOW!!.'Our data show that exposure to male versus female experimenters’ scents induces differential behavioral responses and alters responses to antidepressant-relevant doses of KET in mice.'.
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I am sad to report that a friend, colleague and giant in the field Marc Caron died last night. May he rest in peace.
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I accept the decision of the Editors. if they accepted my paper.
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Non-psychedelic 5-HT2A agonists as antidepressants now @Nature . Congrats to:. @Anat_Levit @BShoichet @RothLabUNC @KuglaeK @LabSkiniotis @PsychoMouse and many others!!. YUUUGE amount of work.
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Whoo hooo! New paper on GPCRs which mediate itch as well as small molecules with which to modulate them in @Nature .Shout out to @CanCao_Natural @Cannabatopia @gori7873 @BShoichet @RothLabUNC .
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And here it is--~100 authors. Thanks to @ahuangxp and others in @RothLabUNC for providing important on- and off-target data!.
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5-HT2A receptor distribution--single light sheet section.#psychedelics .#fluorescentfriday.
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LSD-induced rapid internalization of 5-HT2A receptors--#FluorescenceFriday .Does this occur in vivo?. @RCarhartHarris @DEOlsonLab
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And here it is: how and why DREADD-based chemogenetics works. @hustzsc solved structures with cryo-EM analysis by @Cannabatopia and MD simulations by @rgumpper .Amazing work--have waited since 2005 to understand why DREADDs work as well as they do!.
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And here it is!!.#psychedelic.'These mouse lines represent invaluable tools for elucidating the molecular, cellular, pharmacological, physiological, behavioral, and other actions of psychedelic drugs in vivo.'.
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The only failed experiment is one without the proper controls.
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WOW.". our findings demonstrate brain control of adaptive immunity via direct neural connection.".
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To reiterate: All DREADD resources from @RothLabUNC are open-source. YOU DO NOT NEED TO ASK MY PERMISSION TO USE THEM, SHARE THEM, PUBLISH WITH THEM OR PATENT THEM. Please RT and read as it will save me some time. .
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Whoo hooo!!!.Congrats to all==been waiting for these LSD structures for decades!!.#psychedelic .
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Roth Leads $26.9 Million Project to Create Better Psychiatric Medications — News Room - UNC Health and UNC School of Medicine
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" The full psychedelic effects of LSD are primarily mediated by serotonin 5-HT2A receptor activation.". IN HUMANS!.
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Xylazine is a kappa agonist!!.These findings may help to explain many things related to the xylazine/fentanyl combo which currently is reaching serious proportions in the US. Great work from @nanopharmNC lab!.
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Wow!.Spatial proteomics in neurons at single-protein resolution.
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Wow!.Time-resolved cryo-EM of G-protein activation by a GPCR.Congrats!.
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So I've now hit 90,000 citations. now where is my free coffee mug?
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WOW!.Raptin, a sleep-induced hypothalamic hormone, suppresses appetite and obesity.
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Hundreds of thousands of potential psychedelics discovered by docking against predicted and real structures of 5-HT2A.#psychedelics. "AlphaFold2 structures guide prospective ligand discovery".
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Mice can perceive optogenetic manipulations. regardless of the brain area modulated or the cell type stimulated.
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This is huge!.MAPS PBC Announces Submission of New Drug Application to the FDA for MDMA-Assisted Therapy for PTSD.#psychedelics.
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AND HERE IT IS: "DCZ represents a potent, selective, metabolically stable and fast-acting DREADD agonist with utility in both mice and nonhuman primates for a variety of applications.".
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Sol Snyder discovered:.Opiate receptors.5-HT2A receptors (site of action of LSD).Sigma receptors and most others we know of today.Purified nitric oxide synthase.Discovered mammalian mTOR (Sabbatini was his postdoc at the time).Receptor autoradiography.and so much more. .
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Yuuge amount of work for new sensors for interrogating #gpcr signaling from @RothLabUNC @JustinGEnglish @Reid_dot_com @TaoChe666 and others! Will be available @Addgene .
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Psilocybin for major depression granted Breakthrough Therapy by FDA
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Useful diagram for synaptic plasticity mechanisms.#psychedelics.5-HT2A activates Ca++ --> CAMKII, Rac1, PAK etc
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In our latest paper we discover, literally, 100's of thousands of new 5-HT2A chemotypes as potentially structural novel psychedelics.#psychdelics.
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Scientists Unveil Drug Discovery Tool to Screen More Than 11 Billion Compounds
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The most prescient reviewer comment of all time: . "I cannot imagine what this technology would be useful for." . (rejected grant to develop chemogenetics).
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"We introduce an engineered nanobody whose affinity to green fluorescent protein (GFP) can be switched on and off with small molecules." @JustinGEnglish
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Absolutely not what this paper shows. It shows serotonin does not pass cell membranes. SSRIs do (otherwise they would never get into the brain after oral administration). Also SSRIs cause plasticity but not rapidly like psychedelic drugs.
A new study shows that traditional serotonin-based SSRIs (the current #treatment mode for many mental health conditions) don’t pass neural cell membranes and do not induce plasticity, explaining why SSRIs are largely ineffective for so many patients.
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Professor Roth: "Is it possible to create a non-psychedelic, therapeutically useful 5-HT2A agonist?".@DEOlsonLab @RCarhartHarris @BShoichet
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Cool!.Learning-associated astrocyte ensembles regulate memory recall.
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WOW!!. Chemical proteomics reveals the target landscape of 1,000 kinase inhibitors.
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Latest paper from @chem4biology and @RothLabUNC in @nature --this is a biggie!."Here we investigate structure-based docking of 170 million make-on-demand compounds . we discovered 180-pM subtype-selective agonist of the D4 dopamine receptor.".
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WOW! "Despite loss of the DA signal, optogenetic activation of VTA glutamate cell bodies or axon terminals in NAc was sufficient to support reinforcement.".
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-Striatal 5-HT2A receptors co-localize with mu receptors.-5-HT2A receptors in pyramidal neurons in apical dendrites.-Few 5-HT2A receptors in parvalbumin interneurons
And here it is!!.#psychedelic.'These mouse lines represent invaluable tools for elucidating the molecular, cellular, pharmacological, physiological, behavioral, and other actions of psychedelic drugs in vivo.'.
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Happy to announce I’m an Executive Editor of @BiochemistryACS !! Will be announcing some things that will facilitate your research. #gpcr #chemicalbiology.
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Whoo hooo!! Congrats to Shicheng and members of @RothLabUNC and @BShoichet labs for an amazing and thorough interrogation of the structure, function and pharmacology of 5-HT5A receptors!.
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Wow,wow,wow: ."Chemogenetic activation of dopaminergic neurons in the reward system improved the remodeling processes and vascularization after AMI, leading to enhanced cardiac performance compared to controls.".
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Position available @RothLabUNC to study distribution, structure and function of orphan #GPCR ….and the project is yours to take with you!.Please RT.
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Great work @unc An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice
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Finally--we know how RNA editing alters 5-HT2C serotonin receptor activity!!.Congrats @Cannabatopia @rgumpper .
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Holy crap!."The ability to produce structurally and functionally well-defined transmembrane pores opens the door to the creation of designer channels and pores for a wide variety of applications.". No sh*t!!!!.
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Wow!!.De novo design of drug-binding proteins with predictable binding energy and specificity | Science
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AND HERE IT IS!."This study illustrates opportunities for modulating melatonin receptors . and . the discovery of new, in vivo-active chemotypes from structure-based screens of diverse, ultra-large libraries.". @RothLabUNC @chem4biology . 1/2.
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On the 40th year anniversary of Sargent Peppers Lonely Hearts Club Band I celebrate a NOA just received to study how LSD exerts it’s actions—only took me 20 years to convince reviewers it was an interesting enough topic to fund 🙏🙏.
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The high point of my week--two postdocs have received JOBS!!!.
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#fluorescencefriday.Photo-activated visualization of 5-HT2A-GFP-CT receptors and internalization of surface receptors.#psychedelics
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WOW!.Striatal dopamine mediates hallucination-like perception in mice
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As shown recently a single point mutation in G protein alpha subunit yields a stable complex without the use of stabilizing nanobodies!.
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Please RT.Several postdocs are heading to tenure track positions and I am thus delighted to have openings in my lab for projects related to GPCR structure and function (crystallography, chemogenetics, CRISPR, CLARITY/light sheet microscopy, and in vivo pharmacology). Bryan.
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Finally this is out! Everything you need to know about 5-HT receptors.
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This is a pretty astounding bit of work: discovery of Kir4.1 inhibitor as potential antidepressant.
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Must read for all pharmacologists, chemical biologists and drug-hunters!.A pesky artifact finally revealed!!.
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