Our new paper "Characterization of genetic variants of GIPR reveals a contribution of β-arrestin to metabolic phenotypes " is out in @NatMetabolism . We demonstrate that β-arrestin is central to the function of the #GIP receptor in vitro/vivo. 1/n 🧵👇.

Contribute to the EU-funded Biodiversity2Drugs project, predicting protein-protein interactions across species! 🧬🤖. 🔍 PhD required (bioinformatics, ML, data science, etc.).🛠️ Python/R, protein models, big data handling.📍 Copenhagen | Start: May 2025.

🚨 We’re hiring a #postdoc in Bioinformatics/Data Science/ML! 🚨. Join us in Copenhagen for a postdoc exploring nature-derived drug discovery with AI/ML, genomics, and structural biology. link.

10 more days to apply - come join us in Copenhagen!.

RT @alexshauser: 🚨 🔬 We’re hiring a #postdoc in molecular #pharmacology and #pharmacogenomics! 🧬 If you have a passion for cutting-edge res….

🚨 🔬 We’re hiring a #postdoc in molecular #pharmacology and #pharmacogenomics! 🧬 If you have a passion for cutting-edge research and a drive to explore new frontiers in drug discovery and molecular mechanisms, this could be the perfect fit for you! 💊✨.

/10 Thanks also to the comments and guidance provided by the editors and reviewers and to the support from @koebenhavns_uni and @UCPH_health.

/10 Incredible efforts by the three first authors Sheyma, Kimmie, and Jakob plus help by Peter and Alessandro and all the people involved in this massive collaborative effort especially the teams around Mette Rosenkilde Niels Grarup, Volker Lauschke, and Jonathan E. Campbell.

9/ By studying population mutations as a human evolutionary experiment, we can learn more about #GPCRs and their functional diversity!#pharmacogenetics.

8/ Our findings highlight the significant role of #beta-arrestins in regulating GIPR signaling. Understanding this can aid in preserving biological activity and improve therapeutic targeting of the GIPR system💡.

7/ With orthogonal support in 🐁, we found that genetic ablation of β-arrestin2 impaired cAMP production and decreased GIP efficacy on glucose control in (male) mice.

6/ Prompted by this, we wanted to investigate intracellular signalling capacities. Here we found that variants with maintained β-arrestin 2 recruitment also preserved their Gs-induced signaling from the endosomes. #GPCRs

5/ We could confirm the lower adiposity-related traits associated with reduced GIPR activity, while carriers of variants with maintained β-arrestin recruitment exhibited preserved GIPR function with no changes in their metabolic traits.

4/ Our molecular profiling identified groups of variants with distinct patterns in ligand binding, Gs-activation (cAMP production), and β-arrestin recruitment. Lower cAMP correlated with lower binding capacity, indicating decreased surface expression of the affected variants.

3/ This points to a crucial need to better understand the GIP system. We started by conducting an in-depth pharmacological characterization of 47 missense GIPR variants identified by targeted gene sequencing in ~10,000 Danish individuals with obesity and diabetes. 🧬 #Genetics.

2/ Paradoxically, both activation and inhibition of GIPR, alongside #GLP1R activation, yield similar clinical outcomes as shown by e.g. tirzepatide, AMG-133. 🤔 *Figure from Sheyma

1/ Incretin-based therapies are proving highly effective in addressing obesity and type 2 diabetes (#T2D). But what's fascinating is the role of the glucose-dependent insulinotropic polypeptide receptor (#GIPR) in this process. 👇.

Dopamine D2 receptor isoforms D2Long and D2Short show different magnitude and kinetics of signalling that we present in a new study in @BrJPharmacol. #GPCRs #antipsychotics #Parkinsons.

🚨 Membrane curvature association of amphipathic helix 8 drives constitutive #GPCR endocytosis.