Alessio Ciulli
@alessiociulli.bsky.social
Professor, Founder and Director of the Centre for Targeted Protein Degradation at the University of Dundee. We develop molecules that induce protein interactions and degradation
🔬 In the latest #TIBS50: Foundations and frontiers installment, @alessiociulli.bsky.social and co look to proximity-inducing therapeutics and how the often-underappreciated linker can shape PROTAC function and design. Read their Feature Review: www.cell.com/trends/bioch...
Hear from our 2026 Industry and Academic Collaboration Award winner, Alessio Ciulli @alessiociulli.bsky.social, at Transcription and Chromatin UK in the beautiful medieval city of York, UK, 18-20 November. Early booking deadline is TOMORROW! 🧪 bit.ly/4eWyTmc
Lorraine Reese@lorraine-reese.bsky.social · 2mo agoTranscription and Chromatin UK brings together the rich transcription and epigenetics community in the UK and leading experts from abroad. Most talks will be selected from abstracts and interspersed with invited speaker presentations, submit your abstract before 18 Sept! 🧪 bit.ly/4eWyTmc
A new series of covalent, monovalent glue degraders can co-opt two E3 ligases, DCAF16 and FBBXO22, in a parallel fashion to degrade SMARCA2/4 with chemically and genetically tunable ligase preference www.nature.com/articles/s41...
Dual E3 ligase recruitment by monovalent degraders for tunable SMARCA 2/4 degradation - Nature Chemical Biology
The authors identified a series of covalent, monovalent glue degraders that can co-opt two E3 ligases, DCAF16 and FBXO22, in a parallel fashion to degrade SMARCA2/4 and demonstrated that ligase prefer...
nature.com
Exciting @biorxivpreprint.bsky.social by the groups of @pjcossar.bsky.social and @alessiociulli.bsky.social. They use a molecular glue between 14-3-3 and an intrinsically disordered domain of ERα to develop a molecular glue-based PROTAC recruiting VHL. doi.org/10.1101/2025... #TPD #ChemSky #ChemBio
Induced ubiquitination of the partially disordered Estrogen Receptor alpha protein via a 14-3-3-directed molecular glue-based PROTAC design
Proteins lacking defined ligandable pockets remain challenging drug targets. Here, we develop a molecular glue-based PROTAC (MGPROTACs) approach that chemically conjugates a molecular glue stabilizer ...
doi.org
An absolute pleasure to work with all co-authors on this study: from @alessiociulli.bsky.social’s lab (the 🤝 House of VHL 🤝) @alesalerno.bsky.social & Gajanan Sathe – and our wonderful collaboration Graham Marsh and Hannah Maple from Tocris Bio-Techne
@alessiociulli.bsky.social we are looking forward to your presentation at our #UbiquitinFunction meeting in Portugal ☀️ Please share this with your followers to let them know you will speaking, and to register & submit today to join us! bit.ly/47DJnU2
Get ready for the PROTACS, targeting proteins related to cancer and potentially other diseases a new feature @nature.com www.nature.com/articles/d41...
Excited to share our latest preprint introducing BromoCatch - our cool new Tag solution for protein self-labeling inside cell. This should be a useful addition to the current arsenal of tools eg Halo, Snap. Link to the paper to catch your attention! => www.biorxiv.org/content/10.1...
BromoCatch: a self-labelling tag platform for protein analysis and live cell imaging
Visualizing and manipulating proteins in live cells is crucial for studying complex biological processes. Self-labelling protein (SLP) tags such as HaloTag and SNAP-tag can be fused to genes of intere...
biorxiv.org
Maria Rodriguez-Rios@mariarrios.bsky.social · 2y agoI am delighted to finally share a story that we've been developing at the CeTPD in collaboration with TOCRIS biotechne for the last couple of years! 🎉 We're thrilled to introduce BromoCatch a self-labelling tag platform for protein analysis and manipulation.🔬🧫🧪 www.biorxiv.org/content/10.1...
Delighted to see this, many congratulations and fully deserved! The Boehringer foundation and your colleagues are lucky to have your vision leading this initiative. I am excited as our collaboration will thrive in your new home, and by opportunities for AITHYRA and CeTPD to work together in future
Georg Winter@georgwinter.bsky.social · 2y agoSomething that qualifies as big news from my side: I am very happy and excited to announce that I have been appointed as Life Science Director at AITHYRA, a new Research Institute for Biomedical Artificial Intelligence. Find out more in the link and 🧵 below lnkd.in/d_HaGuSE
Something that qualifies as big news from my side: I am very happy and excited to announce that I have been appointed as Life Science Director at AITHYRA, a new Research Institute for Biomedical Artificial Intelligence. Find out more in the link and 🧵 below lnkd.in/d_HaGuSE
This link will take you to a page that’s not on LinkedIn
lnkd.in
Check-out the first paper from @farnabygroup.bsky.social developing novel chemistry for plate-based PROTAC assembly that in a single Direct-to-Biology (D2B) screen delivers a potent hit that degrades the target protein in the brain of a mouse. Delighted to see this out and kudos to all co-authors
Congratulations to our Keystone Proximity-Based Therapeutics conference travel scholarship winners Christine Ng @stanford-chemh.bsky.social and @alesalerno.bsky.social at CeTPD Dundee! @keystonesymposia.bsky.social
Congratulations to @alesalerno.bsky.social from University of Dundee CeTPD and Christine Ng from @stanford-chemh.bsky.social who have been selected as recipients of our conference travel scholarships to attend the Proximity-based Therapeutics Keystone conference @keystonesymposia.bsky.social!
Collaboration with @supertifurgalab.bsky.social out in @cp-cellchembiol.bsky.social we identify a role of ABCC1 transporter in PROTAC efflux. It turns out, getting in is surprisingly not often the problem; it’s keeping it once inside the cell! Maybe some wider lessons. Designing it out could be key
Superti-Furga Lab@supertifurgalab.bsky.social · 2y agoKicking off the new year: A collaboration between @giuliosupertifurga.bsky.social and @alessiociulli.bsky.social using a transporter-focused genetic screens revealed that the efflux pump ABCC1/MRP1 restricts PROTAC sensitivity in cancer cells. Out now in @CellChemBiol www.cell.com/cell-chemica...
The best way to start 2025: New Year, New Paper! Happy to see (finally!) the science of Amphista therapeutics coming out on @biorxivpreprint.bsky.social Work led by @andre-head.bsky.social and Scott Hughes and congrats to the entire Amphista team involved on the drug development and mode of action.
Andrea Testa@andre-head.bsky.social · 2y agoReally pleased to share this story from Amphista Therapeutics on the discovery and MoA of a potent and selective BRD9 "targeted glue" degrader. The compound also works in vivo and is orally bioavailable! Fantastic work from the team on a super fun project! www.biorxiv.org/content/10.1...
🚨 Exciting News! 🚨 What happens when unconventional ideas drive to push boundaries? 🚀 Meet FerroTACs: a novel #PROTAC design using ferrocene as core unit to re-imagining linker design and fine-tune their phys-chem properties. Learn more about our work led by @alesalerno.bsky.social here: 🧪👇 1/5
ChemRxiv Bot@chemrxivbot.bsky.social · 2y agoRational Design of PROTAC Linkers Featuring Ferrocene as a Molecular Hinge to Enable Dynamic Conformational Changes Authors: Alessandra Salerno, Lianne Wieske, Claudia Diehl, Alessio Ciulli DOI: 10.26434/chemrxiv-2024-1lm1h
Happy to share our latest review on SOCS proteins and their role and therapeutic potential as targets in immunology. To date, drug discovery targeting SOCS proteins have been elusive, due to the difficulty to drug their polar SH2 domain.. 1/3 www.frontiersin.org/journals/imm...
Frontiers | Unravelling the druggability and immunological roles of the SOCS-family proteins
frontiersin.org
That awkward moment when someone publishes a paper saying that they can’t find any evidence that your compounds bind to what your own series of papers say that they bind to. . .
Do They Even Bind?
science.org
So privileged that CHI-Healthtech brought their flagship #DDC conference to Europe, in sunny ☀️ Barcelona! Enjoying tapas and sangria with Heide Düvel @chemb.bsky.social @rpnowak.bsky.social Gopal Sapkota, Ed Tate @nurkocaturk.bsky.social Hannah Peters, Rima Alawar. Thanks for the invitation Tanuja!
Nice write-up of the successful SMART TPD symposium in Shenzhen, China - co-organised with Nat Gray, Nieng Yan, Peng Chan and Shixiang Yan. So enjoyed the opportunity. #TPD #SMARTsymposia www.szbl.ac.cn/en/infomatio...
Just announced: 2025 Computer-Aided Drug Design (CADD) GRC program The topic: "Exploring the Synergy of Machine Learning and Physics-Based Computational Chemistry to Accelerate Drug Discovery" It is shaping up to be a seminal conference. Hope to see you there! www.grc.org/computer-aid...
2025 Computer Aided Drug Design Conference GRC
The 2025 Gordon Research Conference on Computer Aided Drug Design will be held in Portland, Maine. Apply today to reserve your spot.
grc.org
Leveraging Dual-Ligase Recruitment to Enhance Protein Degradation via a Heterotrivalent Proteolysis Targeting Chimera | Collaboration with @georgwinter.bsky.social and Kristin Riching labs. Now published in Journal of the American Chemical Society @acsjacs.bsky.social pubs.acs.org/doi/10.1021/...
Leveraging Dual-Ligase Recruitment to Enhance Protein Degradation via a Heterotrivalent Proteolysis Targeting Chimera
Proteolysis targeting chimera (PROTAC) degraders are typically bifunctional with one E3 ligase ligand connected to one target protein ligand via a linker. While augmented valency has been shown with t...
pubs.acs.org
Dual-ligase PROTACs: a novel approach for enhancing TPD. By recruiting two distinct E3 ligases within a single molecule, we amplify degradation efficacy & potentially mitigate resistance occurrence. Great collabo with the Ciulli lab & friends at Promega. pubs.acs.org/doi/10.1021/...
Leveraging Dual-Ligase Recruitment to Enhance Protein Degradation via a Heterotrivalent Proteolysis Targeting Chimera
Proteolysis targeting chimera (PROTAC) degraders are typically bifunctional with one E3 ligase ligand connected to one target protein ligand via a linker. While augmented valency has been shown with trivalent PROTACs targeting two binding sites within a given target protein, or used to recruit two different targets, the possibility of recruiting two different E3 ligases within the same compound has not been demonstrated. Here we present dual-ligase recruitment as a strategy to enhance targeted protein degradation. We designed heterotrivalent PROTACs composed of CRBN, VHL and BET targeting ligands, separately tethered via a branched trifunctional linker. Structure–activity relationships of 12 analogues qualifies AB3067 as the most potent and fastest degrader of BET proteins, with minimal E3 ligase cross-degradation. Comparative kinetic analyses in wild-type and ligase single and double knockout cell lines revealed that protein ubiquitination and degradation induced by AB3067 was contributed to by both CRBN and VHL in an additive fashion. We further expand the scope of the dual-ligase approach by developing a heterotrivalent CRBN/VHL-based BromoTag degrader and a tetravalent PROTAC comprising of two BET ligand moieties. In summary, we provide proof-of-concept for dual-E3 ligase recruitment as a strategy to boost degradation fitness by recruiting two E3 ligases with a single degrader molecule. This approach could potentially delay the outset of resistance mechanisms involving loss of E3 ligase functionality.
pubs.acs.org
So proud of my former PhD student Tom Webb who defended his thesis with flying colors yesterday! Many thanks to @robvanmontfort.bsky.social from the ICR and Beatriz Baragana from our own Dundee DDU. Also great to host Johan Johansson from AZ it was great to have you visiting us!
Hi everyone! I’m excited to joining this community at @bsky.app BlueSky Social and temperature-test this over the next few months! Looking forward to connecting and sharing with many of you here!
