SINERGIA had 3 Research Objectives (ROs), tackling open issues of the drug development pipeline from different angles, namely "Drug benefit", "Drug safety" and "Precision medicine". All ROs included the development of 5 paradigmatic models, each carried out by an ESR. By using the enabling technologies available in the Consortium, ESRs built these models in the framework of specific PhD programs. In the first year ESRs defined the technical requirements, in the second year they carried out the preliminary validation, while in the third year ESRs exploited the newly developed platforms for biological/clinical validations.
RO1 “Drug Benefit”:
- RO1.1: Andrea Mazzoleni (University of Basel), developed a novel in-vitro model to discover new potential targets for prostate cancer;
- RO1.2: Francesco Niro (ICRC Brno), studied the cardiac fibroblast contribution to myocardial fibrosis in a 3D microscale model;
- RO1.3: Gabriele Addario (University of Maastricht), used bioprinting techniques to to manufacture a tubulointerstitium model to be used in-vitro;
- RO1.4: Riccardo Francescato (Ente Ospedaliero Cantonale), developed an in-vitro model of skeletal muscle tissue to test anti-fibrotic therapies;
- RO1.5: Karol Kugiejko (Politecnico di Milano), developed a multi-compartment microfluidic model to improve gut microbiome-mediated immunotherapy efficiency.
RO2 “Drug Safety”:
- RO2.1: Helen Kearney (University of Maastricht), coupled bioprinting and microfluidics to advance current kidney organoid protocols;
- RO2.2: Ferran Lozano (BiomimX), validated the heart-on-chip device “uHeart” as drug cardiotoxicity screening platform for in-vitro tests;
- RO2.3: Elisa Cauli (Accelera), developed a liver-on-chip model which recapitulated the hepatobiliary environment;
- RO2.4: Hélia Cristina de Barros Fernandes (MTTLab), developed a reusable insert to generate thousands of liver spheroids for drug screening;
- RO2.5: Alicia Ruppelt (LifeTec), developed an ex-vivo perfusion platform able to preserve slaughterhouse-obtained porcine livers in a physiological state.
RO3 “Precision Medicine”:
- RO3.1: Daniel Pereira de Sousa (ICRC Brno), generated patient-specific in-vitro models for a personalized recognition of the key pathway of cardiac fibrosis;
- RO3.2: Evrim Ceren Kabak (University of Basel), coupled in-vivo and in-vitro approaches to study metastatic breast cancer dormancy in bones;
- RO3.3: Anaïs Lamouline (Ente Ospedaliero Cantonale), developed microfluidic bone chips to personalize the therapeutic regimen of bone metastatic tumours;
- RO3.4: Konstantinos Karyniotakis (Aachen University), validated in-vitro models of kidney diseases through specific animal experiments and cell culture trials;
- RO3.5: Rodrigo Torres Garcia (Politecnico di Milano), developed a platform combining electrophysiological, and force contractile measurement in 3D cardiac tissue models.
In SINERGIA, 91 scientific products have been disseminated; of them, 11 are articles in international journals, 42 are abstracts in Conference proceedings. In 8 of the articles, our ESRs were named as first authors or equal-contributing first authors, and more papers are in press.
We provided the ESRs with 3 Summer Schools, and supplementary online training and meetings during Covid. SINERGIA organised a final Workshop event which was open to PhD students from outside the Consortium.