Periodic Reporting for period 1 - UbiCODE (European Research Training to Decipher The Ub Code : identification of potential biomarkers and drug targets)
Reporting period: 2018-01-01 to 2019-12-31
Our key scientific challenge is to investigate how chain diversity is generated (written), regulated (edited), recognised (read) and connected with effector functions (interpreted) to regulate cellular plasticity. Our main hypothesis is that a better knowledge of the “writers”, “editors”, “readers” and “interpreters” of this new universal language will help us to understand the encoded message, which will be crucial to predict physiologic and pathologic processes.
To study chain edition, the role of de-modifying enzymes acting on ubiquitin and Ub-like molecules was investigated by ESRs. Conditions for purification and analysis of the action of proteases acting on NEDD8, SUMO, Ubiquitin were implemented in vitro and in vivo using various cell lines and model organisms. The analysis of their role on chain edition has allowed to reach some of the first conclusions.
UbiCODE fellows have also developed tools and technology to study the specific recognition of distinct ubiquitin-chains containing or not, other UbLs (SUMO or NEDD8), analyse their interactors, subcellular localization and function of modified substrates. Methodologies have been successfully implemented and working conditions set for in vitro and in cellulo analysis using distinct cellular models.
New tools have been developed by ESRs to identify inhibitors of distinct ligases of biomedical interest. This work entails active collaboration between several members of this consortium with complementary expertise. Some progress has been done towards the identification of inhibitors of ligases, the development of new tools for chain identification, as well as towards the identification of exploitation possibilities of new drugs and inhibitors.
UbiCODE PhD students have engaged in an individual reflection on their career goals and expectations from the programme. Daily interaction with experienced researchers from both the academia and the private sector allowed them to clarify their career paths. Fellows will have the opportunity to participate in theoretical workshops to gain transferrable skills (grants writing, communication tools, business development etc.).
- Contribution to structuring doctoral/early stage research training at the European level
Research teams within beneficiary institutions appreciate the quality of the network’s activities and are showing a greater interest in European programmes and funding opportunities. Daily encounters and scientific exchanges within laboratories allow to sensitise non-UbiCODE researchers to the upsides of collaborative research programmes. Interactions with local doctoral schools also contribute to structuring doctoral and early stage research training at the European level by initiating collaborations and sharing practices.
- Strengthening European innovation capacity
Trans-border collaborations are expected to maximise the results and innovation capacity of each participating laboratory, as well as to favour the access to knowledge in the field of ubiquitin research. The programme involves interaction with the private sector, especially with pharmaceutical firms, which will surely enhance translational outcomes. Some UbiCODE research teams are expecting to patent technology and are working on developing spin-off companies.