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PHAGO SIGNED

Inflammation and AD: modulating microglia function focussing on TREM2 and CD33 - Sofia ref.: 115976

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

PHAGO project word cloud

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

plaques tools receptor disease risk assays structures innate cells ectodomain generate neurotoxic ad identification progress cd33 suitable manipulate motility ligands characterisation animals dysfunctional gene animal function neurodegeneration express levels signalling phagocytic interactions microglia modulation attacking limited neuronal innovative phenotype modulating generation inflammation phagocyte simultaneously tau ready treatment onset linked patient reporter age ipsc suggesting regulated knock receptors markers network co amyloid genes drug variants load tangles treatments macrophage immune biomarkers pathological molecular realise ligand models crossed patients multiple vitro trem2 comprehensively imaging brain vivo phago beta expression modification macrophages chronic phagocytes neurodegenerative activation alzheimer fibrillary

Project "PHAGO" data sheet

The following table provides information about the project.

Coordinator	UNIVERSITATSKLINIKUM BONN Organization address address: VENUSBERG-CAMPUS 1 city: BONN postcode: 53127 website: www.ukb.uni-bonn.de 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	Germany [DE]
Project website	https://www.phago.eu/
Total cost	18˙088˙176 €
EC max contribution	8˙838˙000 € (49%)
Programme	1. H2020-EU.3.1.7. (Innovative Medicines Initiative 2 (IMI2))
Code Call	H2020-JTI-IMI2-2015-05-two-stage
Funding Scheme	IMI2-RIA
Starting year	2016
Duration (year-month-day)	from 2016-11-01 to 2021-10-31

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	UNIVERSITATSKLINIKUM BONN UNIVERSITATSKLINIKUM BONN Organization address address: VENUSBERG-CAMPUS 1 city: BONN postcode: 53127 website: www.ukb.uni-bonn.de contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	DE (BONN)	coordinator	1˙754˙200.00
2	KING'S COLLEGE LONDON KING'S COLLEGE LONDON Organization address address: STRAND city: LONDON postcode: WC2R 2LS website: www.kcl.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.	UK (LONDON)	participant	1˙115˙000.00
3	THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE 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.	UK (CAMBRIDGE)	participant	1˙052˙500.00
4	DEUTSCHES ZENTRUM FUR NEURODEGENERATIVE ERKRANKUNGEN EV DEUTSCHES ZENTRUM FUR NEURODEGENERATIVE ERKRANKUNGEN EV Organization address address: SIGMUND FREUD STRASSE 27 city: BONN postcode: 53127 website: www.dzne.de contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	DE (BONN)	participant	1˙027˙500.00
5	UNIVERSITY COLLEGE LONDON UNIVERSITY COLLEGE LONDON Organization address address: GOWER STREET city: LONDON postcode: WC1E 6BT website: n.a. contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	UK (LONDON)	participant	994˙143.00
6	ARTTIC ARTTIC Organization address address: RUE DU DESSOUS DES BERGES 58A city: PARIS postcode: 75013 website: www.arttic.eu contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	FR (PARIS)	participant	593˙750.00
7	CHARITE - UNIVERSITAETSMEDIZIN BERLIN CHARITE - UNIVERSITAETSMEDIZIN BERLIN Organization address address: Chariteplatz 1 city: BERLIN postcode: 10117 website: www.charite.de contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	DE (BERLIN)	participant	538˙750.00
8	FRAUNHOFER GESELLSCHAFT ZUR FOERDERUNG DER ANGEWANDTEN FORSCHUNG E.V. FRAUNHOFER GESELLSCHAFT ZUR FOERDERUNG DER ANGEWANDTEN FORSCHUNG E.V. Organization address address: HANSASTRASSE 27C city: MUNCHEN postcode: 80686 website: www.fraunhofer.de contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	DE (MUNCHEN)	participant	500˙000.00
9	LIFE AND BRAIN GMBH LIFE AND BRAIN GMBH Organization address address: VENUSBERG-CAMPUS 1 city: BONN postcode: 53127 website: www.lifeandbrain.com contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	DE (BONN)	participant	451˙250.00
10	AXXAM SPA AXXAM SPA Organization address address: VIA MEUCCI 3 city: BRESSO MILANO postcode: 20091 website: www.axxam.com contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	IT (BRESSO MILANO)	participant	438˙750.00
11	GOETEBORGS UNIVERSITET GOETEBORGS UNIVERSITET Organization address address: VASAPARKEN city: GOETEBORG postcode: 405 30 website: www.gu.se contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	SE (GOETEBORG)	participant	372˙156.00
12	ABBVIE DEUTSCHLAND GMBH & CO KG ABBVIE DEUTSCHLAND GMBH & CO KG Organization address address: MAINZER STR. 81 city: WIESBADEN postcode: 65205 website: http://www.abbvie.de/ contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	DE (WIESBADEN)	participant	0.00
13	ASTRAZENECA AB ASTRAZENECA AB Organization address address: Vastra Maelarhamnen city: SODERTAELJE postcode: 151 85 website: www.astrazeneca.com contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	SE (SODERTAELJE)	participant	0.00
14	EISAI LIMITED EISAI LIMITED Organization address address: EUROPEAN KNOWLEDGE CENTRE, MOSQUITO WAY city: HATFIELD postcode: AL10 9SN website: n.a. contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	UK (HATFIELD)	participant	0.00
15	Eli Lilly and Company Limited Eli Lilly and Company Limited Organization address address: Lilly House, Priestley Road city: Basingstoke postcode: RG24 9NL website: www.lilly.com contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	UK (Basingstoke)	participant	0.00
16	F. HOFFMANN-LA ROCHE AG F. HOFFMANN-LA ROCHE AG Organization address address: GRENZACHERSTRASSE 124 city: BASEL postcode: 4070 website: www.roche.com contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	CH (BASEL)	participant	0.00
17	H. LUNDBECK AS H. LUNDBECK AS Organization address address: OTTILIAVEJ 7-9 city: VALBY postcode: 2500 website: www.lundbeck.com contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	DK (VALBY)	participant	0.00
18	JANSSEN PHARMACEUTICA NV JANSSEN PHARMACEUTICA NV Organization address address: TURNHOUTSEWEG 30 city: BEERSE postcode: 2340 website: www.janssenpharmaceutica.be contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	BE (BEERSE)	participant	0.00
19	ORION OYJ ORION OYJ Organization address address: ORIONINTIE 1 city: ESPOO postcode: 2200 website: http://www.orion.fi/en/ contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	FI (ESPOO)	participant	0.00
20	SANOFI-AVENTIS RECHERCHE & DEVELOPPEMENT SANOFI-AVENTIS RECHERCHE & DEVELOPPEMENT Organization address address: Pierre Brossolette 1 city: Chilly Mazarin postcode: 91380 website: www.sanofi-aventis.com contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	FR (Chilly Mazarin)	participant	0.00

Map

Project objective

Alzheimer’s disease (AD) is an age-related chronic neurodegenerative disease with four main pathological changes in the brain: amyloid plaques, fibrillary tau tangles, inflammation and neuronal loss. Phagocytes around amyloid plaques in late onset AD (LOAD) may be neurotoxic but have limited motility and phagocytic activity, suggesting a dysfunctional activation. These phagocytes express the innate immune receptor TREM2 and CD33. Variants of both genes have been linked to LOAD. The main objectives of PHAGO are to find means of modulating microglia/macrophage activation via TREM2, CD33 and related signalling pathways, and determine the effects of such modulation on microglia/macrophage function, amyloid-β and neurodegeneration, in order to find a treatment for AD. PHAGO will deliver well characterized tools and knowledge through which to manipulate AD risk and provide targets and markers ready to progress to drug development. PHAGO will realise this goal by comprehensively attacking the problem simultaneously at multiple levels, including the molecular structures of the receptors, receptor ligand interactions, ectodomain function in vitro and in vivo, characterisation of receptor processing, modification and signalling, receptor-regulated signalling pathways, gene expression and phagocyte function in cells and animals, comprehensive analysis of receptor knock-in and knock-out models crossed to two different animal models of AD, and identification of receptor-related biomarkers in AD patients. Innovative approaches of PHAGO will include identification of new AD-risk genes using a TREM2 co-expression network approach, brain imaging of AD patients with TREM2 and CD33 variants, and generation of patient iPSC-derived microglia/macrophages to comprehensively phenotype gene variants. The project will also generate tools, such as ligands, reporter cells and optimised assays, suitable for further development of treatments targeting TREM2 and/or CD33 in AD.

Deliverables

List of deliverables.
Knowledge of possible disease mechanisms and targets	Documents, reports	2020-04-08 21:13:17
Crystal structure of CD33 generated to ~3 Ã… and refined to ~2 Ã…	Documents, reports	2020-04-08 21:13:17
Determination of the cleavage site	Documents, reports	2020-04-08 21:13:16
A comprehensive roadmap for data and knowledge management for the PHAGO consortium, collection of pre-existing ethical documents	Documents, reports	2020-04-08 21:13:17
Press release containing a common part and a part that can be personalised by every partner	Websites, patent fillings, videos etc.	2020-04-08 21:13:16
Launch of website, Twitter and other dissemination activities	Websites, patent fillings, videos etc.	2020-04-08 21:13:17
Completion of the analysis of changes in the glycosylation of TREM2 ectodomains in the presence of R47H variants	Documents, reports	2020-04-08 21:13:17
CD33 receptor ligands characterization in human primary monocytes	Documents, reports	2020-04-08 21:13:17
Providing existing RNAseq signatures and cytokine/chemokine signatures of microglia from tg4510 (tau) mice at various time points	Demonstrators, pilots, prototypes	2020-04-08 21:13:17

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

Publications

List of publications.
year	authors and title	journal	last update
2019	Samira Parhizkar, Thomas Arzberger, Matthias Brendel, Gernot Kleinberger, Maximilian Deussing, Carola Focke, Brigitte Nuscher, Monica Xiong, Alireza Ghasemigharagoz, Natalie Katzmarski, Susanne Krasemann, Stefan F. Lichtenthaler, Stephan A. MÃ¼ller, Alessio Colombo, Laura Sebastian Monasor, Sabina Tahirovic, Jochen Herms, Michael Willem, Nadine Pettkus, Oleg Butovsky, Peter Bartenstein, Dieter Edb Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE published pages: 191-204, ISSN: 1097-6256, DOI: 10.1038/s41593-018-0296-9	Nature Neuroscience 22/2	2020-04-08
2017	Johannes Jungverdorben, Andreas Till, Oliver BrÃ¼stle Induced pluripotent stem cell-based modeling of neurodegenerative diseases: a focus on autophagy published pages: 705-718, ISSN: 0946-2716, DOI: 10.1007/s00109-017-1533-5	Journal of Molecular Medicine 95/7	2020-04-08
2019	Meliha Karsak, Konstantin Glebov, Marina Scheffold, Thomas Bajaj, Amit Kawalia, Ilker Karaca, Sebastian Rading, Johannes Kornhuber, Oliver Peters, Monica Diezâ€Fairen, Lutz FrÃ¶lich, Michael HÃ¼ll, Jens Wiltfang, Martin Scherer, Steffi Riedelâ€Heller, Anja Schneider, Michael T. Heneka, Klaus Fliessbach, Ahmed Sharaf, Holger Thiele, Martina Lennarz, Frank Jessen, Wolfgang Maier, Christian Kubisch A rare heterozygous TREM2 coding variant identified in familial clustering of dementia affects an intrinsically disordered protein region and function of TREM2 published pages: , ISSN: 1059-7794, DOI: 10.1002/humu.23904	Human Mutation	2020-04-08
2019	Antonio Boza-Serrano, RocÃo Ruiz, Raquel Sanchez-Varo, Juan GarcÃa-Revilla, Yiyi Yang, Itzia Jimenez-Ferrer, Agnes Paulus, Malin WennstrÃ¶m, Anna Vilalta, David Allendorf, Jose Carlos Davila, John Stegmayr, Sebastian JimÃ©nez, Maria A. Roca-Ceballos, Victoria Navarro-Garrido, Maria Swanberg, Christine L. Hsieh, Luis M. Real, Elisabet Englund, Sara Linse, Hakon Leffler, Ulf J. Nilsson, Guy C. Bro Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimerâ€™s disease published pages: 251-273, ISSN: 0001-6322, DOI: 10.1007/s00401-019-02013-z	Acta Neuropathologica 138/2	2020-04-08
2019	Luke A. Miles, Stefan J. Hermans, Gabriela A.N. Crespi, Jonathan H. Gooi, Larissa Doughty, Tracy L. Nero, Jasmina MarkuliÄ‡, Andreas Ebneth, Berthold Wroblowski, Daniel Oehlrich, AndrÃ©s A. Trabanco, Marie-Laure Rives, Ines Royaux, Nancy C. Hancock, Michael W. Parker Small Molecule Binding to Alzheimer Risk Factor CD33 Promotes AÎ² Phagocytosis published pages: 110-118, ISSN: 2589-0042, DOI: 10.1016/j.isci.2019.07.023	iScience 19	2020-04-08
2019	Guy C. Brown The endotoxin hypothesis of neurodegeneration published pages: , ISSN: 1742-2094, DOI: 10.1186/s12974-019-1564-7	Journal of Neuroinflammation 16/1	2020-04-08
2018	Bettina Linnartzâ€Gerlach, Liviuâ€Gabriel Bodea, Christine Klaus, AurÃ©lien Ginolhac, Rashi Halder, Lasse Sinkkonen, Jochen Walter, Marco Colonna, Harald Neumann TREM2 triggers microglial density and ageâ€related neuronal loss published pages: , ISSN: 0894-1491, DOI: 10.1002/glia.23563	Glia	2020-04-08
2018	A.E. M. Phillips, C. Villegas Llerena, T.M. Piers, K. Cosker, J. Hardy and J. M. Pocock Loss of Function of TREM2 Results in Cytoskeletal Malfunction in Microglia published pages: , ISSN: 2379-7150, DOI:	Journal of Neurology and Neurobiology Voulme 4 Issue 3	2020-04-08
2017	Peter Thornton, Jean Sevalle, Michael J Deery, Graham Fraser, Ye Zhou, Sara StÃ¥hl, Elske H Franssen, Roger B Dodd, Seema Qamar, Beatriz Gomez Perezâ€Nievas, Louise SC Nicol, Susanna EketjÃ¤ll, Jefferson Revell, Clare Jones, Andrew Billinton, Peter H St Georgeâ€Hyslop, Iain Chessell, Damian C Crowther TREM2 shedding by cleavage at the H157â€S158 bond is accelerated for the Alzheimer\'s diseaseâ€associated H157Y variant published pages: 1366-1378, ISSN: 1757-4676, DOI: 10.15252/emmm.201707673	EMBO Molecular Medicine 9/10	2020-04-08
2017	Kai Schlepckow, Gernot Kleinberger, Akio Fukumori, Regina Feederle, Stefan F Lichtenthaler, Harald Steiner, Christian Haass An Alzheimerâ€associated TREM2 variant occurs at the ADAM cleavage site and affects shedding and phagocytic function published pages: 1356-1365, ISSN: 1757-4676, DOI: 10.15252/emmm.201707672	EMBO Molecular Medicine 9/10	2020-04-08
2018	Guillermo Carbajosa, Karim Malki, Nathan Lawless, Hong Wang, John W. Ryder, Eva Wozniak, Kristie Wood, Charles A. Mein, Richard J.B. Dobson, David A. Collier, Michael J. O\'Neill, Angela K. Hodges, Stephen J. Newhouse Loss of Trem2 in microglia leads to widespread disruption of cell coexpression networks in mouse brain published pages: 151-166, ISSN: 0197-4580, DOI: 10.1016/j.neurobiolaging.2018.04.019	Neurobiology of Aging 69	2020-04-08
2018	Alejandro Carrillo-Jimenez, Mar PuigdellÃvol, Anna Vilalta, Jose Luis Venero, Guy Charles Brown, Peter StGeorge-Hyslop, Miguel Angel Burguillos Effective Knockdown of Gene Expression in Primary Microglia With siRNA and Magnetic Nanoparticles Without Cell Death or Inflammation published pages: , ISSN: 1662-5102, DOI: 10.3389/fncel.2018.00313	Frontiers in Cellular Neuroscience 12	2020-04-08
2018	Xianyuan Xiang, Thomas M. Piers, Benedikt Wefers, Kaichuan Zhu, Anna Mallach, Bettina Brunner, Gernot Kleinberger, Wilbur Song, Marco Colonna, Jochen Herms, Wolfgang Wurst, Jennifer M. Pocock, Christian Haass The Trem2 R47H Alzheimerâ€™s risk variant impairs splicing and reduces Trem2 mRNA and protein in mice but not in humans published pages: , ISSN: 1750-1326, DOI: 10.1186/s13024-018-0280-6	Molecular Neurodegeneration 13/1	2020-04-08
2018	Pablo Garcia-Reitboeck, Alexandra Phillips, Thomas M. Piers, Claudio Villegas-Llerena, Matt Butler, Anna Mallach, Celia Rodrigues, Charles E. Arber, Amanda Heslegrave, Henrik Zetterberg, Harald Neumann, Stephen Neame, Henry Houlden, John Hardy, Jennifer M. Pocock Human Induced Pluripotent Stem Cell-Derived Microglia-Like Cells Harboring TREM2 Missense Mutations Show Specific Deficits in Phagocytosis published pages: 2300-2311, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.07.094	Cell Reports 24/9	2020-04-08

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