GRIB. Research Unit on Biomedical Informatics





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New role of cholesterol in regulating brain proteins discovered

A study led by researchers of GRIB (IMIM-UPF) and the Institute of Medical Physics and Biophysics at the Faculty of Medicine in Charité Hospital, Berlin, published in the journal Nature Communications, demonstrates that the cholesterol present in cell membranes can interfere with the function of an important brain membrane protein, through a previously unknown mode of interaction. Specifically, cholesterol is capable of regulating the activity of the adenosine receptor, by invading it and accessing the active site. This will allow new ways of interacting with these proteins to be devised that in the future could lead to drugs for treating diseases like Alzheimer's.

The adenosine receptor belongs to the GPCR family (G Protein-Coupled Receptors), a large group of proteins located in cell membranes, which are key in the transmission of signals and communication between cells. GPCRs are therefore involved in the majority of important physiological processes, including the interpretation of sensory stimuli such as vision, smell, and taste, the regulation of the immune and inflammatory system, and behaviour modulation.

Explanatory video in which you can see how cholesterol leaves the neuronal membrane and get within the adenosine receptor:

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Nace CompBioMed: un centro de excelencia en biomedicina computacional

Los modelos predictivos de enfermedades están ganando peso en la medicina dada su utilidad a la hora de personalizar los tratamientos. Es por esto que los métodos computacionales basados en la biología humana se han convertido en un factor clave para el desarrollo de la medicina personalizada.

En este escenario ha nacido CompBioMed, proyecto financiado por el programa europeo H2020, un centro de excelencia en computación biomédica que fomenta la captación y explotación de la informática de alto rendimiento (HPC) en el ámbito de la biomedicina liderado por la University College de Londres (UCL). 

Entre los 14 centros que participan en el proyecto se encuentra el grupo de Biofísica Computacional del  GRIB (UPF-IMIM) dirigido por Gianni de Fabritiis, profesor ICREA de la UPF, que jugará un papel importante en el grupo de trabajo 2 del proyecto "Molecularly-based Medicine Exemplar Research", y también en el grupo de trabajo 6, "Empowering Biomedical Applications".

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Last project

CompBioMed is a user-driven Centre of Excellence in Computational Biomedicine, to nurture and promote the uptake and exploitation of high performance computing within the biomedical modelling community: academia, industry and clinical practice. European project funded by H2020 for the period 2016-2019.

http://www.compbiomed.eu/

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Last publications

  • Oddi S, Stepniewski TM, Totaro A, Selent J, Scipioni L, Dufrusine B, Fezza F, Dainese E, Maccarrone M. Palmitoylation of cysteine 415 of CB1 receptor affects ligand-stimulated internalization and selective interaction with membrane cholesterol and caveolin 1. Biochim Biophys Acta, 2017. PMID: 28215712 . DOI: 10.1016/j.bbalip.2017.02.004.
  • Lally CCM, Bauer B, Selent J, Sommer ME. C-edge loops of arrestin function as a membrane anchor. Nature Communications, 2017. PMID: 28220785 . DOI: 10.1038/ncomms14258.
  • Guixà-González R, Albasanz JL, Rodríguez-Epigares I, Pastor M, Sanz F, Martí-Solano M, Manna M, Martínez-Seara H, Hildebrand PW, Martí M, Selent J. Membrane cholesterol access into a G-protein-coupled receptor. Nature Communications, 2017; 8: 14505. PMID: 28220900 . DOI: 10.1038/ncomms14505.
  • Anto JM, Bousquet J, Akdis M, Auffray C, Keil T, Momas I, Postma DS, Valenta R, Wickman M, Cambon-Thomsen A, Haahtela T, Lambrecht BN, Lodrup Carlsen KC, Koppelman GH, Sunyer J, Zuberbier T, Annesi-Maesano I, Arno A, Bindslev-Jensen C, De Carlo G, Forastiere F, Heinrich J, Kowalski ML, Maier D, Melén E, Smit HA, Standl M, Wright J, Asarnoj A, Benet M, Ballardini N, Garcia-Aymerich J, Gehring U, Guerra S, Hohmann C, Kull I, Lupinek C, Pinart M, Skrindo I, Westman M, Smagghe D, Akdis C, Andersson N, Bachert C, Ballereau S, Ballester F, Basagana X, Bedbrook A, Bergstrom A, von Berg A, Brunekreef B, Burte E, Carlsen KH, Chatzi L, Coquet JM, Curin M, Demoly P, Eller E, Fantini MP, von Hertzen L, Hovland V, Jacquemin B, Just J, Keller T, Kiss R, Kogevinas M, Koletzko S, Lau S, Lehmann I, Lemonnier N, Mäkelä M, Mestres J, Mowinckel P, Nadif R, Nawijn MC, Pellet J, Pin I, Porta D, Rancière F, Rial-Sebbag E, Saeys Y, Schuijs MJ, Siroux V, Tischer CG, Torrent M, Varraso R, Wenzel K, Xu CJ. Mechanisms of the Development of Allergy (MeDALL): Introducing novel concepts in allergy phenotypes. J Allergy Clin Immun, 2017; 139(2): 388-399. PMID: 28183433 . DOI: 10.1016/j.jaci.2016.12.940.

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