Melanoma, the deadliest form of skin cancer, is strongly influenced by environmental factors such as UV radiation from ozone depletion. In 2022, there were 331,722 new melanoma cases globally, and by 2040, cases are expected to rise by 50%. A major challenge in treating melanoma is its ability to metastasize, especially when therapeutic targets are unclear or when tumors develop resistance to existing treatments. Recent research findings have identified the nerve growth factor receptor p75NTR as a key player in melanoma progression, invasion, and metastasis, especially in highly metastatic melanoma cells. This project aims to target p75NTR in melanoma cells and extracellular vesicles (EVs) to inhibit melanoma progression. While p75NTR role has been identified in melanoma cells, its role in tumor-derived EVs—responsible for cell communication and metastasis—remains under-explored. This project aims to block p75NTR in both melanoma cells and EVs, where co-receptors and co-effectors availability and cellular interactions differ from that within cells, potentially offering a new therapeutic approach. Leveraging phage display technique, the project will identify peptide ligands specific to p75NTR on melanoma cells and EVs. Outcomes from this Fellowship will benefit several scientific communities, including those working in biomaterials and peptide sciences and, cancer, while providing advanced training and career development opportunities for a young researcher at the intersection of targeted cancer therapies, advanced biomaterials design and peptide technology, preparing her for a leadership role in translational cancer research. By addressing both melanoma cells and EVs, this project introduces a dual-targeted strategy with the potential to transform the understanding of melanoma biology and open new avenues for more effective therapies.

NEUROSENSE proposes a novel and visionary technology resulting from the demonstration of the upstream role of arousal in the sudden unexpected death in epilepsy (SUDEP). SUDEP is a societal challenge for which there is neither prediction nor prevention. Research in the field has for long been refining classic concepts based on the cardiac, respiratory and autonomic nervous systems impairment. Our vision is different and based on the neuroendocrine processes of epileptic seizures and arousal, which are expected to be impaired in SUDEP. The NEUROSENSE project will develop the first SUDEP Medical Device (SMD) prototype supported by artificial intelligence (AI) to anticipate life-threatening seizures and trigger automatic emergency drug administration to prevent SUDEP. This represents the very first viable solution towards a societal-friendly management of epilepsy-derived mortality, thus enabling the prevention of SUDEP worldwide. This will be achieved through the combination of expertise and innovative ideas in epilepsy and SUDEP, biosensors for medical devices, animal models of epilepsy and SUDEP and mathematical modelling. To tackle the objectives of the NEUROSENSE project, a multidisciplinary group of European leading experts in key technological areas will ensure that the complete chain of value is enclosed in a multifaceted analysis. The high-risk character of this joint science and technology research is offset by the multidisciplinary nature of the Consortium, by strong and extensive preliminary data and by the high socio-economic gain resulting from its successful execution. Based in the new SMD technology, we will build a diverse portfolio of future projects that will result in a long-term benefit for people with epilepsy, their families, the economy and society.

TB-SPECTRUM aims to strengthen international research collaboration among different sectors and disciplines, and to structure a network to perform high-quality, translational, and multidisciplinary research for (i) a better understanding of tuberculosis (TB) spectrum immune mechanisms; and (ii) increasing the capacities of the involved staff fostering training and networking activities, as well as increasing their inter-sectoral employability opportunities. Understanding the host-pathogen interactions in the different phases of the spectrum is fundamental for detecting biomarkers of disease progression that can lead to new diagnostic approaches for identifying those individuals with a high-risk of developing disease if infected or for detecting subclinical TB forms. However, it is still unknown which immunological mechanisms are involved in infection/disease progression. To unravel this knowledge gap, it is mandatory to develop collaborative research which combines different expertise in the TB field (clinics, diagnostics, treatment, clinical studies management, cellular/humoral immunology, genomics, and technology transfer, among others). For that purpose, a Consortium of nine academic and non-academic Institutions harboring TB-renowned experts has been constituted. This network is formed by specialists in the clinical management of active TB cases and their contacts (from high and low incident countries); experts in basic/applied science; and a small and medium-sized enterprise (SME) involved in the development of immune assays. Altogether, the proposed goals will be achieved through secondments among the different sectors, which will be extremely important for progressing to a better understanding of the requirements needed in TB management and control; and will expose participants to new research environments that will reinforce multidisciplinarity. Moreover, the interaction with an SME will improve knowledge transference skills, stimulating entrepreneurship.

Innovation makes Europe one of the most socially inclusive and developed regions of the world. A significant public policy effort was put in place to foster science, technology and innovation, while contributing to solve societal challenges. The main purpose is to unleash innovation-led growth that also contributes to reinforce societal values and sustained development. Engaging society with science and innovation has reached a new paradigm with the Horizon Europe Missions. All sectors need to be actively involved in implementing the Missions to reach the expected goals. From schools to companies, from scientific associations to NGOs, all will be called to contribute by co-creating new solutions, products and processes. The new generations are of particular importance. The innovators of 2030 are now being nurtured in schools, supported by science centres, museums and other non-formal education stakeholders. However, many still feel that those spaces are not meant for them. In fact, participants for these science communication activities are drawn from socially dominant groups. We can also infer () who is less likely to participate in science communication: people from socio-economically disadvantaged backgrounds and ethnic minorities (Dawson, 2021). EU-EMBRACES will address this challenge, by engaging those communities while showing how the HE Missions can positively impact their lives. EU-EMBRACES will be developed by a consortium led by ITQB NOVA, a research and academic institution with extensive experience in outreach and event organization, in partnership with Cincia Viva, a national agency dedicated to Scientific Culture; and i3S, a research centre with a solid educational programme for schools and the public. The project will bring together researchers and other stakeholders involved in the HE Missions and the public, in more than 250 activities in 10 venues across the country, with the support of research institutions and local authorities.

Alterations in chromosome number and size are hallmarks of cancer, and yet they are also crucial for species evolution. Recent insight on chromosome structure and segregation, together with significant advances in genomic sequencing, established previously underappreciated parallels between the mechanisms of karyotypic evolution during speciation and cancer. Importantly, alterations in chromosome number and size pose significant challenges for the cell division machinery. However, how dividing cells adapt to cope with karyotypic alterations remains an outstanding fundamental question with strong clinical implications. To address this, we propose an innovative approach that integrates super-resolution microscopy, large-scale 3D cryo-electron tomography reconstructions, computational modelling and cell fusion experiments in Indian and Chinese muntjacs, two closely related deer species with identical genomes, but extremely divergent chromosome number (2n=6/7 vs. 2n=46, respectively) and size. We will focus on dissecting mechanistic aspects underlying mitotic spindle organization, chromosome dynamics, checkpoint control of mitotic progression and segregation fidelity in both muntjac species, with the goal of identifying genes differentially required for efficient mitosis in cells with karyotypic alterations. In parallel, we will exploit functional genomics in Cervidae, including telomere-to-telomere sequencing of Indian and Chinese muntjac genomes, to determine and manipulate the exact chromosome fusion sites between both species, while testing the novel hypothesis of a viral mechanism in the evolution of their karyotypes. Lastly, to test the limits of karyotypic evolution for chromosome segregation, we will engineer mammalian cells with only 1 or 2 chromosomes and investigate whether and how cell division tolerates this extreme genome reorganization. This pioneer work will unveil vital cell adaptive mechanisms to karyotypic evolution relevant for speciation and cancer.