The Instituto de Medicina Molecular João Lobo Antunes (iMM) is a leading European institute in basic biomedical research, now establishing a pioneering Centre of Excellence in human-centred clinical and translational research in Portugal. Research at iMM increasingly requires analysing large volumes of molecular, phenotypic and clinical data but its development is constrained by the national scarcity of experts in biomedical data science. BIOMICS is therefore set on iMM’s strong data-driven research and innovation (R&I) model and investment on the digital transformation of biomedical and clinical research. BIOMICS aims at: 1) leveraging iMM’s excellence in biomedical data science by implementing joint research projects with the partner institutions, strengthening existing interactions and promoting new ones, through staff exchanges, expert visits and joint lab retreats; 2) training a new generation of critically thinking and ethically aware researchers who are able to test scientific hypotheses on biomedical data and soundly interpret their results, through integration in international mentoring networks, facilitating conference and thematic course attendance, and organising on-site training; 3) enhancing international awareness and attract talent to iMM in data science, through mobility of researchers, targeted dissemination and communication activities, and on-site organisation of workshops and an international conference; 4) strengthening iMM’s entrepreneurial and innovation capacity, adapting it to the digital transformation of biomedical and clinical research, through professional technology transfer activities and synergies with the information technology industry. BIOMICS will sustainably leverage iMM’s timely R&I model by supporting the associated digital transformation, making iMM internationally competitive in biomedical data science. Moreover, BIOMICS will provide the partners with a platform for exploring the translational potential of their research.

An important morphogenetic event of mammalian embryogenesis is the formation of a blastocyst with a fluid-filled cavity, blastocoel, and the establishment of three cell types essential for implantation. Morphogenesis of the blastocyst begins with the emergence of multiple nascent cavities, which progressively coalesce to form one cavity segregating the cavity-facing primitive endoderm from the epiblast within the inner cell mass. While cell-to-cell gene expression heterogeneity is well characterised during this lineage specification, little is known about the physical principles governing self-organized blastocyst morphogenesis and patterning. In particular, changes in fluid pressure, cell shape and polarity during blastocyst formation remain uncharacterized. In this project, I will study the roles of fluid cavities in coordinating tissue mechanics, polarity and lineage specification. I will establish a novel micropressure technique to quantify the growth of luminal pressure during blastocyst development. Combining micropipette aspiration with high-resolution live-embryo imaging, I will characterize the impact of fluid pressure on trophectoderm fate specification through dynamic changes in cell shape and adhesion, and cytoskeletal remodeling. To assess the impact of fluid pressure on inner cell mass, I will study if cavity expansion induces apical polarisation and enhances primitive endoderm differentiation in cavity-facing cells. Combining laser ablation with light-sheet microscopy, we will build a spatio-temporal map of intercellular forces in vivo during blastocyst development. We will further manipulate the cavity size to study if fluid pressure is functionally required and sufficient for driving lineage segregation. This interdisciplinary and quantitative study will establish the novel role of fluid cavities and elucidate their interplay with biochemical signaling within the multi-cellular self-organization process.

The social and economic challenges of ageing populations and chronic disease can only be met by translation of biomedical discoveries to new, innovative and cost effective treatments. The ESFRI Biological and Medical Research Infrastructures (BMS RI) underpin every step in this process; effectively joining scientific capabilities and shared services will transform the understanding of biological mechanisms and accelerate its translation into medical care. Biological and medical research that addresses the grand challenges of health and ageing span a broad range of scientific disciplines and user communities. The BMS RIs play a central, facilitating role in this groundbreaking research: inter-disciplinary biomedical and translational research requires resources from multiple research infrastructures such as biobank samples, and resources from multiple research infrastructures such as biobank samples, imaging facilities, molecular screening centres or animal models. Through a user-led approach CORBEL will develop the tools, services and data management required by cutting-edge European research projects: collectively the BMS RIs will establish a sustained foundation of collaborative scientific services for biomedical research in Europe and embed the combined infrastructure capabilities into the scientific workflow of advanced users. Furthermore CORBEL will enable the BMS RIs to support users throughout the execution of a scientific project: from planning and grant applications through to the long-term sustainable management and exploitation of research data. By harmonising user access, unifying data management, creating common ethical and legal services, and offering joint innovation support CORBEL will establish and support a new model for biological and medical research in Europe. The BMS RI joint platform will visibly reduce redundancy and simplify project management and transform the ability of users to deliver advanced, cross-disciplinary research.

The formation of crossovers during meiotic cell divisions is a crucial process to produce sperm and egg cells. This mechanism not only secures proper chromosome segregation but also enhances genetic diversity, playing an essential role in sexual reproduction and evolutionary adaptation. Disruptions in the regulation of crossover events can have detrimental effects on individual organisms and entire species populations. Thus, crossover formation is tightly regulated by both positive and negative pathways. Crossover assurance guarantees that each pair of homologs undergoes at least one crossover, facilitating proper segregation. Simultaneously, crossover interference prevents individual crossovers from occurring too closely within the genome, minimizing the risk of damage. However, the molecular mechanisms of these key regulatory processes and the functional coupling between them are still not understood. To dissect the regulatory mechanisms of crossover formation, we have achieved a groundbreaking visualization of this process in vivo, employing advanced imaging technology and AI-powered image analysis. Our approach includes real-time imaging and correlative super-resolution microscopy for temporal and structural analysis of key steps in crossover formation. In COntrol, I will now exploit these tools to acquire the quantitative data necessary to obtain a mechanistic understanding of crossover regulation. I will develop and rigorously test biophysical models through precisely targeted genetic perturbations, harnessing C. elegans' unique toolset of advanced real-time imaging and genetics. Furthermore, I will validate the uncovered mechanistic principles by examining their conservation in the vertebrate model system zebrafish. COntrol will thus shed light on one of the most fundamental questions in biology, namely how organisms distribute and shuffle genetic information among their progeny while maintaining the genetic integrity of future generations.