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CIRCLE SIGNED

Investigation of the role of CYLD in Chronic Lymphocytic Leukaemia

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

CIRCLE project word cloud

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

link seeking tumours accumulation genes recognition agenda elder lymphocytic deubiquinating transgenic expressed identification cre career crossing record time host techniques indicate mechanisms disease enzyme mice inactivation combines lox publicly acting effect human progenitor cells expertise incidence differentially led suppressor core cll rate rna evaluation falls soft knockout tumour biomarkers emphasis track train leukaemia master first generation pathophysiology data interdisciplinary valuable unravel murine consensus lymphocytes cyld ruling characterization model therapeutic chronic contrasting biology will seq extensively mostly combined emphasizes computational models skills

Project "CIRCLE" data sheet

The following table provides information about the project.

Coordinator	UNIVERSITA VITA-SALUTE SAN RAFFAELE Organization address address: VIA OLGETTINA 58 city: MILANO postcode: 20132 website: www.unihsr.it 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	http://research.hsr.it/en/divisions/experimental-oncology/b-cell-neoplasia/konstantinos-xanthopoulos.html
Total cost	180˙277 €
EC max contribution	180˙277 € (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 2016-04-15 to 2018-04-14

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	UNIVERSITA VITA-SALUTE SAN RAFFAELE UNIVERSITA VITA-SALUTE SAN RAFFAELE Organization address address: VIA OLGETTINA 58 city: MILANO postcode: 20132 website: www.unihsr.it contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	IT (MILANO)	coordinator	180˙277.00

Map

Project objective

This project will investigate the role of CYLD in Chronic Lymphocytic Leukaemia (CLL). CYLD is a deubiquinating enzyme acting as a tumour suppressor in numerous tumours. CLL is characterized by the accumulation of B-lymphocytes. It affects mostly the elder and has a high incidence rate in Europe. Recent data from CYLD knockout murine models indicate a link between CYLD and CLL, however the approach used for generation of these mice led to contrasting results. At the core of this interdisciplinary project is the generation of two transgenic murine with: i) targeted CYLD inactivation in B-lymphocytes, ii) targeted inactivation combined with a murine model of CLL. Targeted inactivation will be achieved using the Cre-Lox system, by crossing already available progenitor mice. The mice will be extensively characterized with an emphasis on B-lymphocytes development and pathophysiology. RNA-seq will be used to find differentially expressed genes in B-lymphocytes. Computational biology approaches will then be applied to identify the affected pathways, which will be evaluated against publicly available human CLL data, seeking wider consensus. CYLD targeted inactivation allows for the first time evaluation of CYLD's role in B-lymphocytes development and CLL ruling out the effect CYLD inactivation in other cells may have. This project will enable better understanding of the role of CYLD in B-lymphocytes biology and could unravel novel biomarkers and therapeutic targets. At the same time the applicant will train-through-research, master novel techniques and develop soft skills valuable for his future career. This project combines the applicant’s expertise in the generation and characterization of murine models with targeted CYLD inactivation with the host's long track record in B-lymphocytes and CLL.It falls well within the EU’s research agenda, which emphasizes interdisciplinary research leading to recognition of common disease mechanisms and identification of novel biomarkers.

Publications

List of publications.
year	authors and title	journal	last update
2017	Konstantinos Xanthopoulos, Alessandra Rovida, Lucia Bongiovanni, Thomas H Winkler, Maurilio Ponzoni and Paolo Ghia The Deubiquitinase Activity of CYLD Is Required for Maturation of B Cells published pages: , ISSN: , DOI:	Blood vol. 130 no. Suppl 1 621	2019-06-13

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The information about "CIRCLE" are provided by the European Opendata Portal: CORDIS opendata.