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RELYUBL SIGNED

Regulation of lymphocyte biology by ubiquitin and ubiquitin like modifiers

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

RELYUBL project word cloud

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

biology function ub ubiquitin enzymes nodes modules proteome immune implied ubls therapies pioneer remove lymphocytes posttranslational biochemical cell ubiquitylation insights phosphorylation substantial limited genetic area severe regulate protein proteins fundamentally focussing dependent modifiers networks disorders modified complexity unknown regulating tightly malignant disrupted ubl discover events differentiation dynamic mice tackled modifications t cells signalling systematically protect daunting roles seeking rewriting immunity give deregulation components deterred regulated immunological vivo adaptive mechanistic inflammation undiscovered full recognition activation pathogens predominantly ultimately disease inform progress ptms elucidate lymphocyte autoimmunity intense hence focussed lymphomas reveal hypothesize

Project "RELYUBL" data sheet

The following table provides information about the project.

Coordinator	UNIVERSITY OF DUNDEE Organization address address: Nethergate city: DUNDEE postcode: DD1 4HN website: www.dundee.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]
Total cost	1˙499˙987 €
EC max contribution	1˙499˙987 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2015-STG
Funding Scheme	ERC-STG
Starting year	2016
Duration (year-month-day)	from 2016-06-01 to 2021-05-31

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	UNIVERSITY OF DUNDEE UNIVERSITY OF DUNDEE Organization address address: Nethergate city: DUNDEE postcode: DD1 4HN website: www.dundee.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 (DUNDEE)	coordinator	1˙499˙987.00

Map

Project objective

T lymphocytes are key cells of the adaptive immune system that protect us against pathogens and malignant cells. T cell activation and differentiation are tightly controlled processes and deregulation can result in lymphomas, autoimmunity and inflammation. Hence, the biochemical events regulating lymphocyte biology have long been a topic of intense research, which has been focussed predominantly on protein phosphorylation. I hypothesize that there are crucial roles undiscovered in T cells for other posttranslational modifications (PTMs) such as ubiquitin (Ub) and Ub-like proteins (UBLs). The importance of ubiquitylation in adaptive immunity is implied by the severe immunological disorders observed when components of the Ub system are disrupted in lymphocytes. Genetic approaches in mice give a limited understanding about the roles of these modifiers and do not reveal the full extent to which Ub and UBLs regulate lymphocyte biology. Deterred by the complexity of the Ub system, the field has not yet tackled the daunting challenge of systematically investigating these modifiers in vivo. The goal of this proposal is to define how T cell function and immune responses are regulated by Ub and UBL signalling networks. To pioneer substantial progress in this area, we will develop new methods to identify and characterize currently unknown recognition modules for the different modifications. We will elucidate the Ub and UBL modified proteome in lymphocytes and characterize dynamic changes of these PTMs during T cell activation. By focussing on enzymes that remove the modifications we will discover how these PTMs are regulated and define Ub and UBL-dependent signalling nodes. Each phase of the work will deliver fundamentally novel mechanistic insights into these PTMs while rewriting current concepts of signalling in lymphocytes. Ultimately, this work will inform therapies seeking to target lymphocyte activity in disease.

Publications

List of publications.
year	authors and title	journal	last update
2018	Dominika Kwasna, Syed Arif Abdul Rehman, Jayaprakash Natarajan, Stephen Matthews, Ross Madden, Virginia De Cesare, Simone Weidlich, Satpal Virdee, Ivan Ahel, Ian Gibbs-Seymour, Yogesh Kulathu Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability published pages: 150-164.e6, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2018.02.023	Molecular Cell 70/1	2019-05-01

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