System omics to unravel the gut-kidney axis in Chronic Kidney Disease: There is a great need for multi-disciplinary and methodologically well trained scientists in order to unravel complex diseases. Chronic kidney disease (CKD), which is more prevalent in women, and its high risk for cardiovascular disease (CVD) with nearly 50% of all deaths in CKD patients caused by CVD, is such a complex disease and its socio-economic burden is extremely high. STRATEGY-CKD will in this context focus on the gut-kidney axis and the role of the intestinal microbiome as important contributor to the genesis and evolution of CVD in CKD and as possible therapeutic target to improve outcome of CKD patients. For this purpose, 10 leading multidisciplinary academic and 3 industrial investigators and their teams will train young researchers in (1) excellent scientific skills, integrating technological skills [in vitro, bacterial and animals molecular and functional studies, state-of-the-art omic (cultur-, microbi, peptid-, prote-, metabolomics) approaches, bioinformatics, systems biology] in clinical/mechanistic knowledge to generate innovative insights triggering the pathogenesis and treatment of CKD related CVD; (2) Excellent complementary skills in personal and career development as well as business training required to extend beyond scientific research; and (3) exposure to both academic and non-academic environments, required to build bridges between researchers and entrepreneurs and support the future translation of research findings in innovative therapies and services. STRATEGY-CKD builds on already available advanced technology, models and patient samples, and established collaborations. STRATEGY-CKD links to ongoing European programs among partners of the consortium. STRATEGY-CKD will stimulate the development of young, broadly-trained scientists able to successfully link basic to clinical research in academia as well as in industry unravelling complex diseases such as CVD-CKD.

Since the approval of the first monoclonal antibody (mAb) 30 years ago, therapeutic mAbs and Ab-derived molecules have come to dominate the biologics market. Currently, +100 Abs are in clinical use for different diseases, out of which +30 mAb target cancer. Despite the huge market potential, multiple and complex steps make the therapeutic Ab discovery process long, expensive, laborious, and inefficient. These steps include target identification, animal immunization, Ab selection and engineering, humanization and preclinical validation. All these are not integrated, costly, require large equipments and facilities, and are highly dependent on experimental animals (mostly mammals, including genetically modified mice), both for immunization and for preclinical validation of the therapeutic Ab candidates. ALADDIN project emerges to bring to the market a novel AcceLerAteD DIscovery Nanobody platform that will increase the efficiency of therapeutic Ab discovery and preclinical validation for human cancer by: 1) integrating selection and in vivo affinity maturation of Abs in bacterial cells holding an universal library of single domain Abs (nanobodies, Nbs) that fully eliminates animal inmunization; 2) using in silico Artificial Intelligent (AI) tools for structure-based epitope mapping, AI-guided affinity maturation, and Nb humanization; 3) developing cost-effective miniaturized microfluidic-based devices for in vitro Ab selection from bacterial cultures; 4) accelerating Ab validation with a fast non-mammalian in vivo model for preclinical testing based on patient-derived tumor xenografts in zebrafish larvae; 5) impacting target and Ab validation with dynamic mathematical models to extract clinical and efficacy data of the Ab candidates. These ambitious goals will be possible through the multidisciplinary ALADDIN consortium, formed by eight partners with complementary skills.

Lymphoid leukemias and lymphomas represent frequent areas of the tumour pathology. Recent Integrative clinical and molecular studies allows to identify concrete disorders where a precise recognition leads to a specific treatment with a minimum toxicity and maximum clinical benefit. Even though there have been many progress during last years, there still persist numerous conditions with low survival probability and high side effects of the received treatments. The introduction of the precision medicine in lymphoid neoplasms is new and challenging due to the scarce knowledge about disease pathogenesis, targeted therapies and predictor markers, immunotherapy role and poor experimental models. T-cell lymphoma tumors present a dismal survival probability dismal (25% for Peripheral T-cell lymphoma) in patients, and the molecular mechanism underlying their high rate of lack response to treatments and relapse is poorly understood. Furthermore, patients with lymphoproliferative disorders often have complex (multiclonal) or mixed lymphoproliferative disorders. This project aim the consolidation of the precision medicine in the diagnosis and therapy of these disorders, thus facilitating the treatment of each patient according its disease, with specific therapy according to the integral characterization of its disease, thus reducing toxicity and improving the therapy efficacy. The project focuses on complex lymphoproliferative diseases characterized by clinical aggressiveness with low therapeutic response, tumor heterogeneity and patterns of dependency / interaction with the microenvironment. The success of the project requires in first instance to improve in the knowledge of the molecular basis of the disease and subsequently in the identification of precise tumour types and patient stratification, thus facilitating the identification of markers for targeted therapy, using gene expression and mutational signatures.