FLEXPOL aims to develop a pilot line for the production of a cost effective antimicrobial (AM) adhesive film for its use in hospitals. The obtained adhesive film will inhibit growth of a wide range of microbes and will be suitable for high-touch surfaces, providing a durable protection with good resistance. It will assure the highest level of hygiene and patient safety, reducing the use of disinfectants. These objectives will be achieved, using a multi-functional approach combining prevention of adhesion with killing of microorganisms, by means of essential oil (EO) emulsions embedded in a micro and nanopatterned polypropylene matrix. FLEXPOL covers the following key aspects: -It addresses the development, upscaling and demonstration in a relevant industrial environment of the production of films with AM, biocompatible and anti-adhesive properties. Existing extrusion and nanoimprinting pilot lines will act as the starting point in which new additives based on blends of EO will be incorporated. -Previously validated technologies constitute the basis of the approach. These technologies will be extended to large scale production and demonstrated in a real operational environment. The pilot line will include real time characterization for inspection of the film at the nanoscale. -Robustness and repeatability of film fabrication and its behavior in a real environment will be studied. The effectiveness of the solution will be compared with standard protocols. -Materials are chosen according to their cost for large-scale application. Productivity and cost of the fabrication process will be analyzed attending to energetic optimization of the product fabrication and the raw material cost. -Access to the pilot line for AM films in this or a different application will be ensured to European Industries at a cost that promotes technology transfer. -Non-technological aspects key for the marketing of the product (such as regulatory issues, HSE aspects, LCA...) are considered.

Women’s cardiovascular health is an urgent clinical unmet need as reported by the European Society of Cardiology (ESC), as cardiovascular disease (CVD) risk in women still tends to be underestimated by clinicians and women themselves. CVD is under-diagnosed, under-treated and poorly understood, more so in women in the 40-60 age group, when personalised risk assessment and prevention can have a positive impact on their health. In this context, CARAMEL will deliver an innovative personalised prevention model aimed at women 40-60yrs based upon a risk assessment stratification model considering sex and gender specific risk factors and a self-assessment and self-management approach using innovative digital technologies, empowering women to optimise their cardiovascular health. The proposed CVD-Risk Assessment and Stratification scheme will only be possible by the cumulative risk factors analysis, fueled by AI, emerging from a wide number of different data sources, including clinical data from EHR, medical imaging, biomarkers, metabolomics, lifestyle information (sleep, physical activity, diet) from large cohorts and biobanks. A consortium composed by 25 partners and Affiliated Entities coming from 11 countries, composed by 9 clinical entities, 6 research organisations and 10 industry and SMEs will develop, test and validate the personalised prevention program in observational and interventional studies in clinical sites in Colombia, Croatia, Greece, Lithuania and Spain. To that end, engagement of women aged 40-60, will take place from the onset on the co-design and co-creation of the studies and the self-management app ecosystem to be developed. Likewise, Gender in research will be mainstreamed all along the intervention. CARAMEL will also deliver policy recommendation and clinical guidelines supporting the design and update of CVD Plans by health authorities and healthcare providers, considering novel AI based risk models, applicable to women aged 40-60 yrs.

Many human diseases, including cancers and inflammatory disorders, are associated with the production of ‘circular DNA’ from chromosomes. These molecules have potential as biomarkers, and in the case of cancers are potential drivers of disease progression. However, the technology for detecting circular DNA and for creating disease models is lacking, meaning we cannot explore their potential use in diagnostics. CIRCULAR VISIONs goal is to explore the new opportunities circular DNA creates in early diagnosis and monitoring of disease, particularly screening, and to create an experimental system to understand the link between disease and circular DNA. CIRCULAR VISION will explore this brand new territory by creating highly sensitive whole genome screens for circular DNA that correlate with disease, using lung cancer (LC) and inflammatory bowel disease (IBD) as model examples. We develop and combine novel methods in molecular biology, microfluidics, DNA sequencing and bioinformatics in order to identify new diagnostic markers. Such markers for IBD and LC will then be adapted to clinical diagnosis and prognosis using advanced image analysis and cytometry methods. Finally, CIRCULAR VISION will show the causal link between circular DNA and cancer, by producing disease models with oncogenes on circular DNA. CIRCULAR VISION assembles key pioneers in the emerging field of circular DNA with leading clinical experts and key commercial players in cytometry and genomics. We are convinced that our technology has broad applications in early noninvasive diagnosis of cancer and monitoring of inflammatory diseases. We believe our technology will lay the foundation for future research into circular DNA biology and spur future drug development.

Age-related neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD), are a major public health problem since there is no effective treatment due to the poor understanding of the pathological processes involved in neuronal death. RNA editing, particularly A-to-I changes mediated by ADAR enzymes, stands as the most prevalent form of post-transcriptional RNA modification. Emerging evidence indicates that the efficiency and pattern of RNA editing in the brain are dynamically regulated during aging and can potentially lead to some neurodegenerative diseases. Despite recent advances in the topic, much remains unknown about how ADAR enzymes regulate RNA-editing and how A to I changes are involved in the onset and development of TDP43 proteinopathies such as ALS and FTD. In ALS, previous studies have described that nuclear clearance of TDP-43 leads to ADAR2 dysregulation and downstream changes in motor neuron RNA editome. However, these results are questioned in other studies using different approaches. Moreover, the function and regulation of RNA editing have not yet been studied in FTD. To address this critical knowledge gap, I will characterize ADAR expression and processing, their protein regulatory network and localization on brain tissue and iPSC-derived from FTD patients and controls. Then, I will describe the resultant RNA editome by applying direct long-read Oxford Nanopore and Illumina RNA-sequencing technologies, coupled with new cutting-edge bioinformatics pipelines. Finally, after identifying the disease-modifying A-to-I events of interest, I will employ antisense RNA strategies to manipulate specific RNA-editing patterns to investigate their function and therapeutic potential in FTD-TDP43. Overall, NeuroEDIT will generate fundamental knowledge to understand the role of RNA editing in neurodegeneration which may result in novel therapeutic targets based on RNA technology.

Cancer dormancy and the trigger to transition to active metastatic growth is a big open question. Current in vivo models focus on niche-specific cell and molecular mechanisms, ignoring biophysical aspects. Dormancy evolves with complex spatio-temporal dynamics; yet, there is a knowledge gap in the understanding of the heterogeneity of the units, and the dynamics of their interaction and evolution. Emergence occurs when a critical mass of units synergistically communicates giving rise to a new macro-level organization, with properties greater than the sum of the units. Engineering emergent phenomena in biological systems is a big research challenge as they originate from multiscale communication. In DORMATRIX, I propose a radically new view. I hypothesize that the balance between cancer dormancy and “awakening” is a collective emergent phenomenon, whereby a critical mass of micro-units communicates with each other and the environment in order to transition to metastatic growth. The main objective of DORMATRIX is to engineer breast cancer (BC) dormancy as a collective emergent phenomenon using biomaterials-based dormancy-on-a-chip devices. My previous data shows that we can (i) apply biophysical cues to control BC proliferation and (ii) visualize in vivo early BC bone metastasis. I will now address this outstanding challenge with a multidisciplinary approach and 1) apply biophysical principles with novel biomaterials to model in vitro cancer micro-units, 2) develop advanced 3D imaging to visualize collective cancer dormancy and bone microdamage, 3) develop in silico models based on evolutionary game theory to predict the dynamics, and 4) prove my hypothesis with dormancy-on-a-chip devices. Understanding the critical mass and multiscale communication required for emergent phenomena will enable the development of novel therapies to delay or prevent metastasis. The resulting technology for engineering emergent phenomena will spark research on other biological systems.