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CollBioImag SIGNED

Development of a cell-based system for high-throughput screening of antifibrotics

Total Cost €

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EC-Contrib. €

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Partnership

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 CollBioImag project word cloud

Explore the words cloud of the CollBioImag project. It provides you a very rough idea of what is the project "CollBioImag" about.

idiopathic    worldwide    electron    responsible    collagen    biosynthesis    cells    organization    alkene    03    stellate    cellular    outcome    tagged    throughput    drugs    compounds    diabetic    herein    models    diels    reaction    preliminary    fibrosis    matrix    incorporation    followed    proteins    suffered    predicted    pulmonary    proline    cell    nonspecific    reactions    enormous    screening    liver    nephropathy    tissue    vivo    antifibrotic    burden    millions    tetrazine    preclinical    proof    demand    metabolic    equipped    function    health    structures    animal    commercial    handles       hepatitis    alder    tag    published    accelerate    pathologies    extracellular    limit    label    collagens    deposition    candidate    diseases    tested    intracellular    reactive    conferred    hepatic    therapeutics    labelling    excess    inverse    consists    derivatives    heart    kidney    library    vasculature    fluorescent    drug    death    cirrhosis    validate    lungs    chronic    world    efficacy    screen    assay    dramatically    selectivity    model    probe   

Project "CollBioImag" data sheet

The following table provides information about the project.

Coordinator
THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE 

Organization address
address: TRINITY LANE THE OLD SCHOOLS
city: CAMBRIDGE
postcode: CB2 1TN
website: www.cam.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Project website https://gbernardeslab.com/
 Total cost 195˙454 €
 EC max contribution 195˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-03-01   to  2018-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE UK (CAMBRIDGE) coordinator 195˙454.00

Map

 Project objective

Liver fibrosis (hepatitis B and C, cirrhosis, etc) represents an enormous health burden responsible for ~1.03 millions death per year worldwide according to the World Health Organization. Fibrosis is also a common outcome of many chronic diseases of the kidney (diabetic nephropathy), lungs (idiopathic pulmonary fibrosis), heart and vasculature (heart failure). In pathologies where fibrosis is a feature, there is an increased deposition of extracellular matrix proteins, including collagens that dramatically limit tissue function. Herein we propose to develop a cell-based assay for high-throughput screening of new antifibrotic therapeutics, which will accelerate fibrosis drug development. Our approach consists in the metabolic incorporation of an alkene-tagged proline in the biosynthesis of collagen, followed by labelling with a fluorescent tetrazine. We recently published preliminary results that provide proof of principle for the use of proline derivatives equipped with reactive handles to tag and label collagen structures. However, this approach suffered from nonspecific reactions of the fluorescent probe with intracellular proteins. The level of selectivity conferred by the proposed inverse-electron-demand Diels-Alder reaction is key in enabling its use in cells. We will use hepatic stellate cells since these cells are responsible for excess collagen production during liver fibrosis. To demonstrate that the cellular model can be used to screen compounds for fibrosis we will validate our system using a library of compounds with known preclinical antifibrotic activities. We will test if their in vivo efficacy can be predicted using cells. If our findings are significant we will use this cellular model to screen a commercial available library of compounds to find new antifibrotic drugs. The efficacy of the best candidate will be tested in vivo using two animal models of induced fibrosis.

 Publications

year authors and title journal last update
List of publications.
2018 Maria J. Matos, Bruno L. Oliveira, Nuria Martínez-Sáez, Ana Guerreiro, Pedro M. S. D. Cal, Jean Bertoldo, María Maneiro, Elizabeth Perkins, Julie Howard, Michael J. Deery, Justin M. Chalker, Francisco Corzana, Gonzalo Jiménez-Osés, Gonçalo J. L. Bernardes
Chemo- and Regioselective Lysine Modification on Native Proteins
published pages: 4004-4017, ISSN: 0002-7863, DOI: 10.1021/jacs.7b12874
Journal of the American Chemical Society 140/11 2019-06-13
2018 Benjamin Stenton, Bruno Oliveira, Maria Matos, Laura Sinatra, Gonçalo J. L. Bernardes
A Thioether-directed Palladium-cleavable Linker for Targeted Bioorthogonal Drug Decaging
published pages: , ISSN: 2041-6520, DOI: 10.1039/C8SC00256H
Chemical Science 2019-06-13
2017 Ester Jiménez-Moreno, Zijian Guo, Bruno L. Oliveira, Inês S. Albuquerque, Annabel Kitowski, Ana Guerreiro, Omar Boutureira, Tiago Rodrigues, Gonzalo Jiménez-Osés, Gonçalo J. L. Bernardes
Vinyl Ether/Tetrazine Pair for the Traceless Release of Alcohols in Cells
published pages: 243-247, ISSN: 1433-7851, DOI: 10.1002/anie.201609607
Angewandte Chemie International Edition 56/1 2019-06-13
2017 B. L. Oliveira, Z. Guo, G. J. L. Bernardes
Inverse electron demand Diels–Alder reactions in chemical biology
published pages: 4895-4950, ISSN: 0306-0012, DOI: 10.1039/c7cs00184c
Chemical Society Reviews 46/16 2019-06-13
2016 Barbara Bernardim, Pedro M.S.D. Cal, Maria J. Matos, Bruno L. Oliveira, Nuria Martínez-Sáez, Inês S. Albuquerque, Elizabeth Perkins, Francisco Corzana, Antonio C.B. Burtoloso, Gonzalo Jiménez-Osés, Gonçalo J. L. Bernardes
Stoichiometric and irreversible cysteine-selective protein modification using carbonylacrylic reagents
published pages: 13128, ISSN: 2041-1723, DOI: 10.1038/ncomms13128
Nature Communications 7 2019-06-13
2016 Zijian Guo, Bruno L. Oliveira, Omar Boutureira, Ana Guerreiro, and Gonçalo J. L. Bernardes
A minimal, unstrained S-allyl handle for protein site-selective modification.
published pages: , ISSN: , DOI:
EMBL conference 2016, Heidelberg, Germany. 2019-06-13
2016 Oliveira BL, Guo Z, Boutureira O, Guerreiro A, Jiménez-Osés G, Bernardes GJ
A Minimal, Unstrained S-Allyl Handle for Pre-Targeting Diels-Alder Bioorthogonal Labeling in Live Cells.
published pages: 14683-14687, ISSN: 1521-3773, DOI: 10.1002/anie.201608438
Angew Chem Int Ed Engl. 55(47) 2019-06-13

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