T-cells are a special type of white blood cells, which are essential to fight tumours, bacterial and viral infections and also important in the development of both autoimmunity and allergies. For T-cells to develop into functionally competent, mature white cells, immature cells from the bone marrow have to migrate to the supporting environment of the thymus, where they undergo a complex selection and differentiation programme. The thymus consists of various cell types, but thymic epithelial cells are the key supporting cells for T-cell development. Without thymic epithelium there is no T-cell development. Thymic epithelial cells provide several survival, and differentiation factors for immature T-cells, including the secreted glycoprotein family, Wnt. Generally, Wnt signals are known to regulate cell functions from cell proliferation through cell migration to cell differentiation. Our preliminary data shows, that in contrast to other factors secreted by the thymic epithelium, epithelial cells can also respond to Wnt signals. This suggests, that Wnt-s are important in maintenance and differentiation of the thymic epithelium arguing that Wnt-s can not only regulate T-cell development directly, but also indirectly via modulating epithelial cell survival and differentiation. Despite its importance, very little is known about the way Wnt-s influence the function of thymic epithelial cells. This project will study the effects of Wnt-s on thymic epithelial cell development and function, and will focus on one of the key enzymes, PKC. This knowledge will lead to better understanding of T-cell development, which is important in devising strategies to influence specific T-cell output as and where it becomes necessary in treatment of diseases.

Optical microscopy has been central to biology for centuries. In recent decades fluorescence microscopy has developed as an exceptionally sensitive and universally employed tool in the life sciences. Its power was dramatically enhanced in the 1990s through the discovery of the green fluorescent protein (GFP). This allowed a fluorescent label (GFP) to be irreversibly and selectively expressed attached to a specific target protein, permitting the location, dynamics and function of that protein to be probed in a living cell. More recently, photoswitchable fluorescent proteins were discovered. These fluorescent proteins can be reversibly switched between fluorescent (on) and nonfluorescent (off) states by light. This property allowed the development of super-resolution fluorescence bioimaging, which improved the spatial resolution of fluorescence microscopy by more than 10 times, allowing details much smaller than the wavelength of light to be observed in living systems. However, applications of photoswitchable proteins are limited because the light used to generate fluorescence from their 'on' states also switches the proteins 'off', causing the image to fade. A higher level of control is offered by the recently discovered third generation fluorescent proteins (3G FPs), which have three states, an off-state and a switching state in thermal equilibrium with an on-state. These three states can be independently excited, so switching off is decoupled from observation from the on-state. This development will lead to enhanced super-resolution imaging, and has the potential for the development of new multicolour imaging methods. However, the mechanism connecting these states is completely unknown. Our experiments will allow us to probe in detail the effects of light on all three states of 3G FPs. We will measure the rates of the interconversion between the three states as well as the structural changes that accompany them. Since the fastest of the interconversion reactions are extremely fast (thousand-billionths of a second) we will use the tools of ultrafast laser spectroscopy to make our observations. Our ultrafast experiments probe populations of reactant, intermediate and product states through their absorption spectroscopy, while their structures are probed through ultrafast vibrational spectroscopy. These measurements will lead to a detailed picture of the photoconversion mechanism in 3G FPs. Once the mechanism is established, we will apply the tools of chemical biology to make mutations in key residues that will (i) test our ideas of the mechanism and (ii) optimise the photoswitching rate, and thus yield superior 3G FPs for bioimaging. Photoactive proteins such as FPs offer a unique opportunity to observe protein structure evolution in real time. In particular time resolved vibrational spectroscopy yields structural data from femtoseconds out to milliseconds. This information has great importance, as it can be compared with the results of computational calculations and independent experiments on protein structural dynamics. Together this will yield the most detailed insights yet into the dynamics of proteins undergoing their function, which in turn enhances our understanding of the nature of drug-protein interactions.

<< Background >>Palliative care (PC) “is fundamental to human dignity and a component of the human right to health” (Resolution 2249 – 2018 of the European Parliamentary Assembly) and this is why education and training on PC are essential components of undergraduate medical education. Nevertheless, PC is not yet fully developed in the EU and the lack of services and teachers with a specific expertise in the PC domain also hamper the design and implementation of effective educational programs on PC for undergraduate students. Worldwide, many countries developed a core competencies catalog for PC at the undergraduate level and, in Europe, the European Association for Palliative Care (EAPC) issued a White Paper listing and discussing the core competencies on PC education.The various forms of technology-enhanced learning and – more in particular – synchronous and asynchronous online learning are promising pedagogies to foster effective teaching of the PC core competencies, overcoming the constraints of resources, at least for most of the cognitive and technical- manual learning outcomes and for the basic relational skills.<< Objectives >>The main goal of the ELPIS project is to enhance the quality of PC in the EU through a better and more uniform education at the undergraduate level. This goal is relevant not only because of the already mentioned importance of PC, as stated by the European Parliament but also because of the increasing cross-border mobility of medical graduates across the Union, seeking both post-graduate education and occupation. To achieve this goal, the ELPIS project has five intertwined objectives:1. to promote the design of internally coherent and comparable online undergraduate medical education programs on PC, through the development of a theoretical educational framework2. to promote effective implementation of online programs on PC, through the development of practice guidelines that are flexible enough to be- suitable for the local organizational context of higher education and PC- fit for the local cultural approach to palliative care and other end-of-life issues, including the students’ point of view3. to broadcast sharable educational resources, in different European languages4. to validate the theoretical framework and guidelines through testing and comparing the effectiveness of some local implementations of an online program on PC5. to design and implement faculty development programs to sustain the design of curricula in PC and the use of the educational resources<< Implementation >>The ELPIS project has four Work PackagesWP 1: DEFINITION OF THE THEORETICAL FRAMEWORK AND DRAFTING OF THE COURSE ON PCThis WP will define a theoretical educational framework to design an online undergraduate course on Palliative Care (PC). We chose the realist synthesis method to develop the theoretical framework from international literature. The final result of a realist review is a “final program theory”. The final output of WP1 will be the template of a course, ready to be reviewed by the experts of each partner institution. The structure of the template will be: according to the program theory, for this type of educational outcome, in this type of context, this type of structure of the course, use of technology, teaching, learning and assessment activities is likely to be the best choice.The theoretical framework and the draft design of an online course on PC are valuable products in themselves, addressed to all teachers in the field of PC education.WP2: EDUCATIONAL DESIGN AND IMPLEMENTATION OF THE LOCAL COURSESThe aim of WP2 is to develop and implement the local online courses on PC of the seven participating partners. The courses will be comparable, because they are based on the same template, but also adapted to the local organizational and curricular context. WP2 will also account for the production of the contents (text, exercises, tests of assessment) of the course both in English and in each partner’s language. The WP has three steps.1. The structure of each local training course will be designed, according to the general template developed in WP1. The course will aim to achieve two learning outcomes: a cognitive outcome of high taxonomic level (prescribing, planning, managing) and a relational-communication outcome. 2. The contents of the courses will be developed. The contents of all six courses will be translated into English language, to have an English version of every course, which will act as a template for possible further national translations in the future. Every single course will be delivered in the national local language (Italian, German, Hungarian, Romanian, Spanish) for local use. 3. Six partners will implement the course for delivery, according to the resources and rules of the local level, ready to be offered to the students in the experimental phase.WP3: PILOT & TESTING OF THE LOCAL COURSESThe aim of the WP3 is to empirically validate the theoretical framework through testing and comparing the effectiveness of the local implementations of the online courses on PC.The partners will run a quasi-experimental trial with a group of students attending the online course and a control group attending face-to-face teaching. The educational outcomes and the course contents will be the same, the two courses will differ only for the method of delivery and the implicated differences in the activities. WP4: QUALITY ASSURANCE OF DATA, STATISTICS AND ELECTRONIC REPOSITORY OF CONTENTSThis WP is aimed to assure the quality of experimental data and to gather the data and all the produced electronic contents (texts, exercises, tests).validation of the instruments for the assessment of learning outcomes. creation and delivery of a survey on students’ satisfaction of the course (both online and face-to-face), perception of relevance, utility, difficulty, self-confidence about the outcome.design and creation of an electronic repository for all the produced and tested contents. The repository will have a web interface and will be accessible to all academic centers and palliative care facilities involved in training, upon free registration. design of Faculty development programs for the design and implementation of online courses<< Results >>The results of the ELPIS project will be:-a theoretical framework to describe elements and methods for an effective design of online PC courses.-practice guidelines for the implementation and assessment of PC courses at the undergraduate level.-a core of multilingual educational resources in an open access repository-new knowledge and perspectives about the feasibility and comparative effectiveness of different forms of online learning vs in face-to-face learningThe outcome will be the impact of the ELPIS project on the target categories: undergraduate medical students and teachers at medical schools. We shall also consider the impact on the other relevant stakeholders: the national academic and scientific community, political decision-makers, the resonance of the information media. We expect an increase in knowledge and clinical skill in students participating in both online and face-to-face courses. We also expect a high level of student's satisfaction with the online course. If a substantial equivalence is demonstrated, this will increase the propensity of teachers to use online teaching to overcome the lack of resources (few hospices) and the ethical problems of exposing end-of-life patients to a large number of students.The multiplier events that will run during the project will raise the awareness of the academic community and local political stakeholders on the importance of education and policies for end-of-life.

<< Objectives >>The main intended achievement of the PRO-ME-ToM project is to provide a well-elaborated and tested developmental program for improving metacognitive and Theory-of-MinD (ToM ) skills' awareness, a crucial skill for a meaningful participation in the information society. Tests and description of in-class activities translated to five languages will be available for use to teachers form primary and secondary education in order to improve students' metacognitive thinking and ToM skills.<< Implementation >>There will be constructed assessment tools for evaluating metacognitively aware thinking of teachers and students from the primary and secondary education level. A 12-week training program will be developed to promote teacher’s metacognitive awareness and to build their capacity to teach metacognitive skills. The measurement tool and training program will be available in five languages (Greek, Romanian, Hungarian, Portuguese and English)<< Results >>During the PRO-ME-ToM project 30 primary and 30 secondary teachers from each participating country will be trained about how to use the developed metacognitive training program and measurement tools. Approximately 150 primary and 150 secondary school students from five countries will be empowered with the key competence of metacognitive thinking by participating in a developmental program. Tools for measuring and improving metacognition in school settings will be available in five languages.