T cells play a central role in anti-tumor immune protection. While their ability to target and eliminate emerging tumor cells is increasingly recognized, fully-established tumors can efficiently evade T cell response. Significant efforts spanning several decades of research have been made to develop T cell-based therapies manufactured from donor-derived T cells. The use of tumor-directed T cells engineered to express chimeric antigen receptors (CARs) represents, to date, one of the most successful applications for treatment of chemoresistant cancers. However, several major drawbacks, including economic factors, suboptimal functioning and life-threatening side effects, are still hindering the full potential of T cell-based therapies. To address this issue, we aim to generate Artificial T cells (ArTCell) that will mimic the anti-tumor function of a T cell-based therapy but in a safer, more efficient and less expensive product. ArTCells will incorporate two key features of activated T cells into Giant Unilamellar Vesicles (GUVs): the specificity of tumor cell recognition and the cytotoxic activity achieved through death ligands and cytolytic proteins. Functionalization of the GUVs will be confirmed by immunofluorescent labelling of membrane proteins (i.e., TRAIL, LFA-1 and CAR) and detection with flow cytometry. The morphology of ArTCell will be monitored via cryo-EM, SEM, and confocal microscopy. The ability of ArTCell to target and kill tumour cells will be thoroughly validated in vitro by a combination of functional and high resolution live imaging assays as well as in vivo with two cell line- and patient-xenografts mouse models. The ArTCell could allow to circumvent many of the current technological limitations that hinder a more wide-spread applicability of cell-based therapies, without being subject to tumor-mediated inactivation

The COVID-19 pandemic caught the world unprepared. Vaccines and monoclonal antibodies (mAbs), developed in record time, mitigated the health and economic damages, however our reaction has always been one step behind the virus evolution, and emerging variants repeatedly escaped our interventions. The omicron variant escaped humoral immunity generated by most vaccines and mAbs by mutating immunodominant epitopes. The extremely potent mAb developed by our laboratory also lost potency against omicron. Here we propose to develop vaccines and monoclonals neutralizing existing and future variants of SARS-CoV-2 and other coronaviruses, by targeting immunologically subdominant regions which are less susceptible to antigenic variation. We will isolate mAbs from individuals who had infection and multiple vaccinations, whose repertoire is enriched in B cells encoding broadly neutralizing antibodies, to build a map of the broadly shared epitopes. Structural prediction and clustering of the immune repertoire through deep neural networks will be used to improve the breadth of coverage of the mAbs. The Monte Carlo-based sequence design of Rosetta and free energy perturbation calculations will be used to in-silico “design protein-binding proteins” and identify newly designed immunogens which can be loaded on nanoparticles and used as vaccines. This approach will provide broadly protective mAbs and vaccines proactively designed to neutralize all variants of SARS-CoV-2 and new coronaviruses that are very likely to jump from animals to humans in the future. If successful, the approach to map subdominant epitopes and use of genomic and structural information to design mAbs and vaccines targeting subdominant, broadly conserved epitopes, will pave the way to approach other pathogens with high antigenic variability such as influenza and HIV viruses, Plasmodium spp. and antibiotic resistant bacteria. This will strongly increase European competitiveness in fighting infections.

The project SCIENCE is born on the basis of previous projects, always in LLP-Leonardo da Vinci IVT contest, made by the Sarrocchi, and this year it involves all professional profiles of the school (chemical thecnician; construction technician; electronic technician; computing technician; mechanical and mechatronic technician) because of the widespread interest in the mobility proposed in previous school years.It has been developed by the school and matured in the context of Siena area, which has seen in the recent years a deep economic and social development, but also in a European context..The project will contribute to meet the needs of various actors, physical and legal, of the local territory in general: the students of the Institute, many companies in the sectors related to these areas of study, education institutions, public bodies responsible for economic development, education and connection to school and work.The basic need is to train a new generation of experts (connected to the above mentioned profiles), in order to possess the skills needed because of the rapid evolution of technology (including the UE key competence of the language, personal growth, transversal abilities and the professional skills ...) . Therefore we believe that the participants would get concrete answers to the need to update, professionalization, improvment of skills and operational capabilities, through an international internship.More specifically, the aims of the participants, will focus on the acquisition/improvemento of:- skills related to the professional profile (different for each profile) - language and UE key competences (same for all the profiles)- transnversal (same for all the profiles)Objectives of the promoter and the partnership are:- to increase the quality of training- to expand and improve the skills of their students- to make students more employable- to connect the world of school to work in order to meet the needs of the local and European market.- to promote the use of ECVET tools in the recognition of mobility experiencesExpected results include increased training and employability of the participants, an increased efficiency of company partners who may have qualified and updated staff, an improvement of the courses offered by the Institute Sarrocchi in terms of quality and European dimension.The participants will be 70 students (4 with special needs) and 8 accompanying teachers (2 for participants with special needs):The expected flows are as follows:Jan-Feb 2015: Paragon Europe Malta (1 flow): 14 learners Jun-Jul 2015: AIP and Oneco Spagna (2 flows) 14 learnersSep-Oct 2015: ECTARC Galles and InternEurope Belfast (UK) (2 flows)14 + 14 learnersJun-Jul 2016: Globtrain Berlino (D) (1 flow) 14 learners.The project will have a total duration of 24 months.Project partners are: public entities, SME connected to the sectors of the projects, vocational trainingn institutes. For project management Sarrocchi the Institute, in its fifth experience of project management LLP-Leonardo da Vinci IVT will use its tools and instruments of T-TACTIC@SCOOL manual for the management of international internships for schools.