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Toll-Like Receptor 4 activation and function in diseases: an integrated chemical-biology approach.

Total Cost €


EC-Contrib. €






 TOLLerant project word cloud

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

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Project "TOLLerant" data sheet

The following table provides information about the project.


Organization address
city: MILANO
postcode: 20126

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 Italy [IT]
 Project website
 Total cost 3˙122˙539 €
 EC max contribution 3˙122˙539 € (100%)
 Programme 1. H2020-EU.1.3.1. (Fostering new skills by means of excellent initial training of researchers)
 Code Call H2020-MSCA-ITN-2014
 Funding Scheme MSCA-ITN-ETN
 Starting year 2015
 Duration (year-month-day) from 2015-01-01   to  2018-12-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
3    KEMIJSKI INSTITUT SI (LJUBLJANA) participant 469˙995.00
4    VIB BE (ZWIJNAARDE - GENT) participant 250˙560.00
5    UNIVERSITAET BIELEFELD DE (BIELEFELD) participant 249˙216.00
9    DIOMUNE SL ES (MADRID) participant 247˙872.00
10    LOFARMA S.P.A. IT (MILAN) participant 129˙030.00


 Project objective

Based on an international team derived from the COST action BM1003 (, 2011-2014) and thus relying on consolidated group interactions and synergies and on a unique combination of chemistry, biology, biophysics, biochemistry and pharmacology expertise, the TOLLerant project aims to gain information on molecular aspects of TLR4 activation and signaling by using synthetic and natural compounds and nanoparticles that interact selectively with some components (mainly MD-2 and CD14) of the TRL4 recognition system. TLR4 is an emerging molecular target related to an impressively broad spectrum of modern day disorders still lacking specific pharmacological treatment. These include autoimmune disorders, chronic inflammations, allergies, asthma, infectious and CNS diseases and cancer. The short-term scientific objective is to develop novel, non-toxic, synthetic and natural TLR4 modulators (agonists or antagonists) and to assess their therapeutic potential on animal models of TLR4-related acute and chronic pathologies that still lack efficient pharmacological treatment. The long-term scientific objective is to develop a new generation of innovative, TLR4-based therapeutics, to be used as vaccine adjuvants, anti-sepsis agents, and anti-inflammatory agents to treat chronic inflammations (allergy, asthma). The training programme will provide Early Stage Researchers (ESR) with broad competences, experience and skills in the cutting-edge, inter-disciplinary research in the field of chemical biology related to the molecular mechanisms of innate immunity and inflammation. During the training, the young researchers will be supported by senior scientists to cultivate their scientific, entrepreneurial and inter-cultural mindset. The non-academic sector will be committed to provide ESRs with entrepreneurship and company management skills, in order to enhance their employability by the private sector or even to motivate them to create own start-up companies.


List of deliverables.
Agenda Documents, reports 2019-07-22 08:10:45
TOLLerant website Websites, patent fillings, videos etc. 2019-05-22 20:37:28
Annual agenda of outreach activities Documents, reports 2019-07-22 08:10:53
Progress, periodic, midterm and final reports Documents, reports 2019-07-22 08:10:46
Minutes of training events Documents, reports 2019-07-22 08:10:45
TOLLerant linkedIn group Websites, patent fillings, videos etc. 2019-05-22 20:37:28
Consortium quarterly newsletter Documents, reports 2019-07-22 08:10:51
Training reports Documents, reports 2019-07-22 08:10:48
Protocols for molecular modelling Demonstrators, pilots, prototypes 2019-05-22 20:37:28
Dissemination plan Documents, reports 2019-05-22 20:37:29

Take a look to the deliverables list in detail:  detailed list of TOLLerant deliverables.


year authors and title journal last update
List of publications.
2017 Florent Cochet, Francesco Peri
The Role of Carbohydrates in the Lipopolysaccharide (LPS)/Toll-Like Receptor 4 (TLR4) Signalling
published pages: 2318, ISSN: 1422-0067, DOI: 10.3390/ijms18112318
International Journal of Molecular Sciences 18/11 2019-06-05
2017 Flaviana Di Lorenzo, Angelo Palmigiano, Katarzyna A. Duda, Mateusz Pallach, Nicolas Busset, Luisa Sturiale, Eric Giraud, Domenico Garozzo, Antonio Molinaro, Alba Silipo
Structure of the Lipopolysaccharide from the Bradyrhizobium sp. ORS285 rfaL Mutant Strain
published pages: 541-553, ISSN: 2191-1363, DOI: 10.1002/open.201700074
ChemistryOpen 6/4 2019-06-05
2018 Clara Barrau, Flaviana Di Lorenzo, Rodolfo Menes, Rosa Lanzetta, Antonio Molinaro, Alba Silipo
The Structure of the Lipid A from the Halophilic Bacterium Spiribacter salinus M19-40T
published pages: 124, ISSN: 1660-3397, DOI: 10.3390/md16040124
Marine Drugs 16/4 2019-06-05
2017 Flaviana Di Lorenzo, Angelo Palmigiano, Ida Paciello, Mateusz Pallach, Domenico Garozzo, Maria-Lina Bernardini, Violetta La Cono, Michail M. Yakimov, Antonio Molinaro, Alba Silipo
The Deep-Sea Polyextremophile Halobacteroides lacunaris TB21 Rough-Type LPS: Structure and Inhibitory Activity towards Toxic LPS
published pages: 201, ISSN: 1660-3397, DOI: 10.3390/md15070201
Marine Drugs 15/12 2019-06-05
2018 Fabio A. Facchini, Lenny Zaffaroni, Alberto Minotti, Silvia Rapisarda, Valentina Calabrese, Matilde Forcella, Paola Fusi, Cristina Airoldi, Carlotta Ciaramelli, Jean-Marc Billod, Andra B. Schromm, Harald Braun, Charys Palmer, Rudi Beyaert, Fabio Lapenta, Roman Jerala, Grisha Pirianov, Sonsoles Martin-Santamaria, Francesco Peri
Structure–Activity Relationship in Monosaccharide-Based Toll-Like Receptor 4 (TLR4) Antagonists
published pages: , ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.7b01803
Journal of Medicinal Chemistry 2019-06-05
2018 Flaviana Di Lorenzo, Angelo Palmigiano, Sami Albitar-Nehme, Mateusz Pallach, Maxim Kokoulin, Nadezhda Komandrova, Lyudmila Romanenko, Maria Lina Bernardini, Domenico Garozzo, Antonio Molinaro, Alba Silipo
Lipid A Structure and Immunoinhibitory Effect of the Marine Bacterium Cobetia pacifica KMM 3879 T
published pages: 2707-2716, ISSN: 1434-193X, DOI: 10.1002/ejoc.201800279
European Journal of Organic Chemistry 2018/20-21 2019-06-05
2018 Fabio A. Facchini, Helena Coelho, Stefania E. Sestito, Sandra Delgado, Alberto Minotti, David Andreu, Jesús Jiménez-Barbero, Francesco Peri
Co-administration of Antimicrobial Peptides Enhances Toll-like Receptor 4 Antagonist Activity of a Synthetic Glycolipid
published pages: 280-287, ISSN: 1860-7179, DOI: 10.1002/cmdc.201700694
ChemMedChem 13/3 2019-06-05
2018 Lenny Zaffaroni, Francesco Peri
Recent advances on Toll-like receptor 4 modulation: new therapeutic perspectives
published pages: , ISSN: 1756-8919, DOI: 10.4155/fmc-2017-0172
Future Medicinal Chemistry 2019-06-05
2019 Giordano Traini, Ane Ruiz-de-Angulo, Juan Bautista Blanco-Canosa, Kepa Zamacola Bascarán, Antonio Molinaro, Alba Silipo, David Escors, Juan C. Mareque-Rivas
Cancer Immunotherapy of TLR4 Agonist-Antigen Constructs Enhanced with Pathogen-Mimicking Magnetite Nanoparticles and Checkpoint Blockade of PD-L1
published pages: 1803993, ISSN: 1613-6810, DOI: 10.1002/smll.201803993
Small 15/4 2019-06-03
2017 Matilde de las Rivas, Erandi Lira-Navarrete, Earnest James Paul Daniel, Ismael Compañón, Helena Coelho, Ana Diniz, Jesús Jiménez-Barbero, Jesús M. Peregrina, Henrik Clausen, Francisco Corzana, Filipa Marcelo, Gonzalo Jiménez-Osés, Thomas A. Gerken, Ramon Hurtado-Guerrero
The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-017-02006-0
Nature Communications 8/1 2019-05-22
2019 Giordano Traini, Ane Ruiz-de-Angulo, Juan Bautista Blanco-Canosa, Kepa Zamacola Bascarán, Antonio Molinaro, Alba Silipo, David Escors, Juan C. Mareque-Rivas
Cancer Immunotherapy of TLR4 Agonist-Antigen Constructs Enhanced with Pathogen-Mimicking Magnetite Nanoparticles and Checkpoint Blockade of PD-L1
published pages: 1803993, ISSN: 1613-6810, DOI: 10.1002/smll.201803993
Small 15/4 2019-05-22
2018 Luigi Lembo-Fazio, Jean-Marc Billod, Flaviana Di Lorenzo, Ida Paciello, Mateusz Pallach, Sara Vaz-Francisco, Aurora Holgado, Rudi Beyaert, Manuel Fresno, Atsushi Shimoyama, Rosa Lanzetta, Koichi Fukase, Djamel Gully, Eric Giraud, Sonsoles Martín-Santamaría, Maria-Lina Bernardini, Alba Silipo
Bradyrhizobium Lipid A: Immunological Properties and Molecular Basis of Its Binding to the Myeloid Differentiation Protein-2/Toll-Like Receptor 4 Complex
published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2018.01888
Frontiers in Immunology 9 2019-05-22
2018 Fabio Lapenta, Jana Aupič, Žiga Strmšek, Roman Jerala
Coiled coil protein origami: from modular design principles towards biotechnological applications
published pages: 3530-3542, ISSN: 0306-0012, DOI: 10.1039/c7cs00822h
Chemical Society Reviews 47/10 2019-05-22
2017 Ajasja Ljubetič, Fabio Lapenta, Helena Gradišar, Igor Drobnak, Jana Aupič, Žiga Strmšek, Duško Lainšček, Iva Hafner-Bratkovič, Andreja Majerle, Nuša Krivec, Mojca Benčina, Tomaž Pisanski, Tanja Ćirković Veličković, Adam Round, José María Carazo, Roberto Melero, Roman Jerala
Design of coiled-coil protein-origami cages that self-assemble in vitro and in vivo
published pages: , ISSN: 1087-0156, DOI: 10.1038/nbt.3994
Nature Biotechnology 2019-05-22
2018 Mateusz Pallach, Flaviana Di Lorenzo, Fabio Alessandro Facchini, Djamel Gully, Eric Giraud, Francesco Peri, Katarzyna A. Duda, Antonio Molinaro, Alba Silipo
Structure and inflammatory activity of the LPS isolated from Acetobacter pasteurianus CIP103108
published pages: 1027-1035, ISSN: 0141-8130, DOI: 10.1016/j.ijbiomac.2018.08.035
International Journal of Biological Macromolecules 119 2019-05-22
2019 Florent Cochet, Fabio A. Facchini, Lenny Zaffaroni, Jean-Marc Billod, Helena Coelho, Aurora Holgado, Harald Braun, Rudi Beyaert, Roman Jerala, Jesus Jimenez-Barbero, Sonsoles Martin-Santamaria, Francesco Peri
Novel carboxylate-based glycolipids: TLR4 antagonism, MD-2 binding and self-assembly properties
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-018-37421-w
Scientific Reports 9/1 2019-05-22
2016 Beatriz Salvador, Alicia Arranz, Sara Francisco, Laura Córdoba, Carmen Punzón, Miguel Ángel Llamas, Manuel Fresno
Modulation of endothelial function by Toll like receptors
published pages: 46-56, ISSN: 1043-6618, DOI: 10.1016/j.phrs.2016.03.038
Pharmacological Research 108 2019-06-05
2016 Jean-Marc Billod, Alessandra Lacetera, Joan Guzmán-Caldentey, Sonsoles Martín-Santamaría
Computational Approaches to Toll-Like Receptor 4 Modulation
published pages: 994, ISSN: 1420-3049, DOI: 10.3390/molecules21080994
Molecules 21/8 2019-06-05

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