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An explanatory image showing the pathway of cholesterol from the membrane into the discovered binding site on the neurotransmitter receptor. Source:IMIM.

17/09/2021

Researchers of GRIB show that cholesterol is fundamental for signal transmission in the human brain

Researchers from the GPCR Drug Discovery Group of GRIB have discovered a novel mechanism through which the serotonin receptor interacts with cell membranes in the human brain. This finding opens the door for the design of novel drugs

A study lead by researchers from the GPCR Drug Discovery Group of GRIB and the Centre for Cellular and Molecular Biology of the Council Of Scientific And Industrial Research (CSIR) published in the Science Advances journal, shows for the first time how cholesterol can interfere with the function of a important receptor present in brain cells - the serotonin receptor. This finding is of great importance, as it allows to devise new ways to modulate those receptors, which in the future could lead to the development of new drugs to treat diseases of the central nervous system.

In this study, researchers demonstrate, for the first time, how cholesterol influences the function of serotonin receptors at an atomic scale. This finding describes the structural basis of a yet undescribed cross-talk between those receptors and the membrane. "Until know it was not clear how the presence of cholesterol influences the behavior of those proteins, due to the lack of methods that can capture the dynamics of such biological events at an atomic scale" explains Dr Jana Selent, the head of the GPCR Drug Discovery Group, and the co-supervisor of the study. "The results of our study show the intimate relation between cholesterol and GPCRs of the central nervous system and highlight the key role of this molecule in signal transmission within the brain" she adds. "Our findings pave the path for novel lines of investigation, like the use of membrane components as tools to treat disorders of the central nervous system"

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The C. elegans brain with all neurons expressing green fluorescent protein (GFP), and a subset of neurons involved in feeding expressing a magenta nuclear marker. Scale bar is 10 microns. (Seth Taylor)

31/08/2021

Research Snapshot: First-ever gene expression map of an entire nervous system completed

researchers share data to expedite research into genetic defects affecting the brain

Extracted from Research news of Vanderbilt University website

Professors Seth Taylor and David Miller, both in Vanderbilt University's Department of Cell and Developmental Biology, along with biologists from ​Col​umbia University​, Yale University ​and IMIM ​have established a gene expression atlas for the nervous system of the nematode C. elegans. Gabriel Santpere, head of the Neurogenomics research group of GRIB has collaborated on this work. 

Their data complement the known wiring diagram of the C. elegans nervous system to create, for the first time, a complete picture of gene expression for every neuron in an entire nervous system.

The article "Molecular topography of an entire nervous system" was published online in the journal Cell on July 7.

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09/11/2021

Open Innovation Modelling Challenge

The eTRANSAFE consortium is happy to invite the world-wide scientific community to the Open Innovation Modelling Challenge. Consortium partners, Universitat Pompeu Fabra and University of Vienna, developed model building tools which allow easy transfer and validation of computational models at other partner's premises, including EFPIA companies. The focus of this challenge lies on off-target modelling. The best model(s)/results will be published and promoted by the eTRANSAFE consortium.

The models shall be built only with one of these eTRANSAFE tools UNIVIE Sandbox / KNIME Workflow and Flame

To learn more about these tools and our challenge we kindly invite you to join our workshops on 17 of November:

UNIVIE Sandbox/KNIME: 17th November 2021 at 10:00 - 14:30 CET
Flame: 17th November 2021 at 16:00 - 18:00 CET.

Go to registration form

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09/08/2021

Mechanism that triggers brain neurone response revealed

It is the first time it has been possible to see how neurotransmitters and proteins interact at the atomic level to trigger neuronal responses.

Researchers from the G-protein-coupled receptor-based drug discovery research group of GRIB (IMIM-UPF), led by Dr. Jana Selent have been able to verify, with a degree of precision never before achieved, how the process that triggers the response of neurones in the brain occurs. This is an essential mechanism for understanding how moods or even processes such as addictions are produced, and in which neurotransmitters, molecules that help transmit information between neurones through specialised receptors, the G protein-coupled receptors (GPCRs), play a vital role.

"Neurotransmission is one of the most crucial physiological processes, as its dysregulation can result in various neuropsychiatric disorders", explains Dr. Jana Selent, principal author of the study, published in the journal Chemical Science, and coordinator of the research group that led the work. Very small changes in how information is transmitted by these molecules can trigger different reactions in the brain, some of which are linked to behaviour, addictions and moods.

Reference article: Stepniewski TM, Mancini A, Agren R, Torrens-Fontanals M, M Semache, Bouvier M, Sahlholm K, Breton B, Selent J. Mechanistic insights into dopaminergic and serotonergic neurotransmission-concerted interactions with helices 5 and 6 drive the functional outcome. Chem Sci, 2021 DOI: 10.1039/D1SC00749A.

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7/7/2021

RISK-HUNT3R project launches: risk assessment of chemicals integrating human centric next generation testing strategies promoting the 3Rs

RISK-HUNT3R is the new European effort hosting world-leading experts from many different disciplines aiming to develop a novel and modular framework for animal-free next generation risk assessment (NGRA). The Integrative Bioinformatics and PharmacoInformatics groups of GRIB, led by Ferran Sanz and Manuel Pastor respectively, take part of this project. Also the company MedBioinformatics Solutions, an spin-off of the GRIB, is partner of ​RISKHUNT3R

Over the past decades, science and society have increasingly started demanding a paradigm shift towards chemical safety and risk assessment without using animals. In addition to growing ethical concerns around the use of animal studies, there is the fundamental need to address all potential health effects relevant and specific to humans. Furthermore, the limited efficiency of animal-based testing (low throughput, high costs, insufficient laboratory capacity) will not be able to keep up the pace in ensuring the required protection of European citizens based on the sheer number of chemicals that require safety assessment. The vision of the RISK-HUNT3R consortium is to establish a reliable and cost-effective chemical risk assessment strategy based entirely on non-animal approaches. 

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06/07/2021

Thesis defence of Joaquim Aguirre: ​"​In silico tools to study diseases and polypharmacology through the lens of network medicine​"​

​Next ​Wednesday 14th of July​ at ​11​:​00, ​Joaquim Aguirre, member of the Structural Bioinformatics group of GRIB will read his thesis ​​"​In silico tools to study diseases and polypharmacology through the lens of network medicine

The event will be online. Free access at https://us02web.zoom.us/j/83124036086

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22/06/2021

GRIB participates in a new world-wide initiative that paves the way for the large-scale annotation and characterization of small proteins in the genome

The first results of the international 'Non-canonical ORF Working Group' to annotate novel translated open reading frames (ORFs) in the human genome have been made publicly available. The initiative includes researchers from 37 different Institutions, including Mar Albà, ICREA researcher at the Research Programme on Biomedical Informatics (GRIB, IMIM-UPF), and former PhD student, Jorge Ruiz-Orera. The latter researcher, now at the Max Delbrück Center,  co-leads the project together with researchers at the European Bioinformatics Institute and the Broad Institute. The effort also has the support of Gencode/Ensembl, HGNC and Uniprot.

The researchers have collected data from already published studies and built a consensus list that contains 7,264 new translated ORFs, including many ORFs in long non-coding RNAs, as well as upstream ORFs (uORFs) in coding transcripts. The list will be accessible from the Gencode web page and, in subsequent phases of the project, it will be part of standard gene annotations. The project paves the way for the large-scale annotation and characterization of small proteins that have remained hidden in the genome. A more complete annotation of the human proteome will be key to identify mutations that inactivate small proteins and cause disease.

Preprint: Mudge, Ruiz-Orera, Prensner et al. A community-driven roadmap to advance research on translated open reading frames detected by Ribo-seq. bioRxiv June 10, 2021.

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Imagen de Alberto Meseguer

28/06/2021

​Thesis defence of Alberto Meseguer: "Methods to model and assess protein-DNA and protein-protein interactions in the context of gene regulation".

​Next Friday, 2nd of July at 10:00, Alberto Meseguer, member of the Structural Bioinformatics group of GRIB will read his thesis "Methods to model and assess protein-DNA and protein-protein interactions in the context of gene regulation". 

The event will be online. Free access at:​​https://us02web.zoom.us/j/8198872626

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22/06/2021

Open GRIB seminar on June, 22nd: Bioinformatics, combining facility and research by Lara Nonell

The last Open GRIB seminar took place on 22/06/2021 at 10:00 h with the title "Bioinformatics, combining facility and research", by Dr Lara Nonell, member of MARGenomics at IMIM and researcher of the Human Computational Biology group of the Programme on Biomedical Informatics-GRIB (IMIM/UPF).

Abstract

Bioinformatics is a common need in most research labs. Therefore it is important to have access to a core facility that is able to implement the standard methodology to extract knowledge from biological data, including omics data. In addition, new methods are continuously developed in the field to meet increasing data analysis demands. In this context, we will explain our experience as a service oriented facility and will also see some of the recently funded projects we are involved in, coming out of fields as disparate as COVID-19, bladder cancer or major depression disorder.

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26/05/2021

Proyecto PROMPT: Hacia una medicina de precisión para la predicción de la respuesta al tratamiento del trastorno depresivo mayor

El GRIB inicia este nuevo proyecto liderado por la Universidad de Muenster (Alemania) en el que participan los investigadores Ferran Sanz, Lara Nonell y Laura I. Furlong. El objetivo es desarrollar herramientas predictivas que faciliten la toma de decisiones en el tratamiento del trastorno depresivo mayor, mejorando la prevención y gestión de esta enfermedad.     

El trastorno depresivo mayor (TDM) es la enfermedad psiquiátrica más común en todo el mundo con un enorme impacto socioeconómico. La farmacoterapia representa la primera opción de tratamiento; sin embargo, esta solo tiene éxito en alrededor del 33% de los pacientes mientras un 30% se manifiestan resistentes al tratamiento lo cual se asocia con características clínicas o genéticas específicas. 

Este proyecto representa una prueba de concepto. Los resultados obtenidos proporcionarán información sobre la viabilidad y utilidad del enfoque propuesto, con el objeto de diseñar ensayos clínicos futuros en los que los algoritmos puedan ser probados como una herramienta predictiva para apoyar la toma de decisiones de los médicos, lo que permitirá una mejor prevención y gestión de la resistencia al TDM.

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