Want to help shape the future of Cambridge? 🧐
Join students from across the University for the Cambridge Student Summit – a day of interactive discussions, workshops, and student-led conversations with local leaders and community organisations.
📅 Thursday 18 June, 9.30am–4pm
📍 Cambridge Guildhall
🎫 Free to attend (limited spaces available)
🍴 Lunch and refreshments provided
Book your place now 👉 https://t.co/2zWwS4fgkS
Indigenous Peoples are at the 💚 of protecting some of the most vital ecosystems on Earth.
They live on and manage roughly 22% of the world’s land, territories that overlap with many of the planet’s most biodiverse and ecologically intact areas. https://t.co/XEml4VIRyp
We may speak thousands of languages, but we all call this planet home.
No matter where we come from, protecting our Earth is a shared responsibility.
We need more ambitious #ClimateAction — for our planet and the generations to come.
— via @UNDP
A unified ensemble-allosteric framework reconciles gain- and loss-of-function disease mutations in the IP3 receptor
1. The study proposes a single ensemble-allosteric model to explain why nearby missense mutations in IP3R1 can cause opposite phenotypes (gain-of-function vs loss-of-function) while the N-terminal fold remains largely intact.
2. By combining in silico saturation mutagenesis with ProteinMPNN/ThermoMPNN and AlphaMissense, pathogenic substitutions are shown to cluster in a “stability-preserving but locally incompatible” regime: mutations tend to disrupt local sequence–structure compatibility without strongly destabilizing the global N-terminal architecture.
3. This reframes IP3R1 channelopathy: disease is driven less by unfolding or structural collapse, and more by corruption of conformational probabilities and allosteric information flow linking ligand recognition to gating.
4. Using BioEmu to sample 1,000 conformations per variant (filtered to retain native-like SD–IBC architecture), the IP3-binding pocket is shown to occupy a discrete multi-basin conformational landscape. Clustering in a pocket-local UMAP embedding identifies three reproducible pocket substates (A–C).
5. Loss-of-function variants tend to reweight these pre-existing pocket substates rather than creating entirely new structures. The LOF mutation R269W shows the strongest redistribution, markedly enriching a rare pocket substate and depleting the WT-dominant one.
6. Pocket physicochemistry explains the R269W LOF mechanism: replacing a cationic IP3-coordinating Arg with bulky Trp reduces pocket volume, lowers positive/charge character, and increases hydrophobicity—changes that are unfavorable for binding a highly phosphorylated ligand like IP3.
7. Adaptive MD (2 μs aggregate per system) plus Markov state models reveal that WT pocket dynamics form a connected three-state kinetic network with efficient exchange. R269W preserves three metastable states but reroutes transitions: exchange from a minor to dominant basin becomes predominantly intermediate-mediated, reducing direct kinetic connectivity between key pocket basins.
8. In contrast, the GOF suppressor-domain mutation R36C keeps a broadly WT-like pocket ensemble and more WT-like pocket kinetics, arguing that GOF does not require local pocket “activation” or collapse. Instead, its effect is distal and allosteric.
9. Contact-informed dynamical network analysis links R36C GOF to weakened suppressor-domain restraint: SD-to-pocket communication is redistributed onto longer, less efficient pathways (increased weighted shortest-path cost), with rewiring of residues/edges near pocket-adjacent loops and altered community organization—consistent with allosteric decoupling rather than pocket failure.
📜Paper: https://t.co/OCyXAenbqv
#ComputationalBiology #MolecularDynamics #Allostery #ProteinEnsembles #MarkovStateModels #CalciumSignaling #Neurogenetics #IP3R #ITPR1 #VariantInterpretation
Today we wish Bob Dylan a happy 85th birthday.
Listen to this excerpt from Dylan's Nobel Prize lecture where he reflects on the literary influences that shaped his songwriting. Classic works like 'Moby-Dick', 'All Quiet on the Western Front', and 'The Odyssey' informed his understanding of storytelling and human nature.
Hear the full lecture: https://t.co/cFBj6dwoff
very pleased to see this online near-final version. Really enjoyed collaborating with the Moreno group on this exciting project and glad that I could contribute
https://t.co/io2o7P35CU
Thinking about postgraduate study at Cambridge as an international student? 🤔
Our international postgraduate funding webinar series is a deep dive into our scholarships and awards available to international students, including opportunities from Cambridge Trust, Gates Cambridge, and regional partners.
Don't miss the opportunity to understand your funding options and join the session in your time zone! ⏰
Register today through the link 👉 https://t.co/cEtdfAsumY
#CambridgeUniversity #Cambridge #Postgraduate
Metformin, one of the most commonly prescribed drugs, was thought to work via the liver. Check that. It's primarily through the gut. @NatMetabolism
https://t.co/i2CpZip61B
'Interstitial cells of Cajal – pacemakers of the #gastrointestinal tract'
Kenton M. Sanders (@unrmed), L. Fernando Santana (@ucd_physiology) & Salah A. Baker summarise key mechanisms responsible for electrical rhythmicity in gastrointestinal organs⚡️🔎
https://t.co/RY1BAE4Nzf
if you are interested in ion channels, calcium signalling or computational biophysics and eligible for the fellowship application, feel free to be in touch:
https://t.co/dL3IGCg1du
🔬Fully funded PhD
Applications are open for the BBSRC–GSK Transformative Technologies in Pharmaceutical Science programme!
Apply by 15 May 2026
👉https://t.co/2a36uNSpsS
#PharmaceuticalScience#CambridgeUniversity#GSK
Are you 19 or over and now thinking about university for the first time? 💭
Cambridge 21+ is a hybrid residential programme, run by @Hughes_Hall, @WolfsonCam and @StEdmundsCam, for mature students who have never been to university before 🏫
Sign up now 👇
https://t.co/dQoKPQSqlw