Cohesin is an evolutionarily conserved multi-protein complex that belongs to the structural maintenance of chromosomes protein family. It can topologically entrap DNA molecules mediating sister chromatid cohesion, a function important for accurate chromosome segregation and DNA replication/repair. It has been recently discovered that cohesin can generate and maintain DNA loops by an ATPase-dependent in cis DNA tethering activity, called loop-extrusion, critical for organising chromatin architecture and regulating gene transcription, and as such thought to be important for cell differentiation and development. However, the molecular mechanisms by which the cohesin complex achieve these key cellular functions remain to be elucidated. Mutations in genes coding for cohesin and its regulators lead to a class of developmental disorders collectively called “cohesinopathies” and have been found in several types of cancer. Nonetheless, the pathogenesis of these devastating human diseases is poorly understood. CohesiNet aims to answer outstanding questions in the field of cohesin biology by a highly innovative research programme. This consortium will investigate fundamental mechanisms on how cohesin acts during chromosomal cohesion and loop extrusion, identify regulatory modules of cohesin functions and get insights into the molecular bases of cohesin-related diseases. These ambitious goals will be achieved using multi-disciplinary hypothesis-driven and exploratory approaches while promoting a culture of communication and cooperation among academic and private institutions across the European Union. A team of ten PhD students will be trained by the CohesiNet consortium to address these scientific questions and be empowered with skills that will enhance their career perspectives, while experiencing first-hand the value of Open Science and the importance of inclusion, transparency, accessibility and integrity in scientific research.

Ovarian Cancer (OC) is the most lethal gynecological tumor and has an especially high impact in Europe. 70% of patients develop an advanced stage due to the lack of early diagnosis tools and chemotherapy resistance. Therefore, a better understanding of altered molecular mechanisms driving OC progression is needed. Preliminary data from the host lab suggest that a complex formed by R2TP/TTT/WAC upon glucose and glutamine depletion, impairs mTOR activation. Moreover, the components of this complex are co-expressed in OC, a disease influenced by mTOR signaling and metabolic reprogramming. Thus, our hypothesis is that WAC regulates an mTOR activation pathway that influences OC progression and response to chemotherapy and that targeting this complex is a potential therapeutic prospect for the treatment of OC. In particular, we propose to (i) establish the mechanism and role of the R2TP/TTT/WAC/mTOR complex in OC and (ii) to identify new therapeutic strategies targeting this complex for the treatment of OC. We have envisioned this project as a diverse node of cancer signaling and protein experts, with a predicted outcome highly transferable to society. The translational character of this proposal, from molecular mechanism to therapeutics, relies on the integration of an interdisciplinary team formed by the host group proficiency in Structural Biology and my expertise in Molecular Biology and Drug Discovery, together with scientific experts on Experimental Therapeutics and Bioinformatics from the host institution and collaborators. Importantly, I will have the opportunity to develop new professional skills by both scientific exchanges and specific courses and to participate in dissemination activities to translate our findings to the scientific community and society. Thus, the MSCA fellowship will allow me to develop unique technical and transferable skills, to help me progress in my career developmental plan and establish myself as a leader in cancer research in Europe.

Recent years witness an upsurge in the quantities of digital research data, offering new insights and opportunities for improved understanding. Text and data mining is emerging as a powerful tool for harnessing the power of structured and unstructured content and data, by analysing them at multiple levels and in several dimensions to discover hidden and new knowledge. However, text mining solutions are not easy to discover and use, nor are they easily combinable by end users. OpenMinTeD aspires to enable the creation of an infrastructure that fosters and facilitates the use of text mining technologies in the scientific publications world, builds on existing text mining tools and platforms, and renders them discoverable and interoperablethrough appropriate registriesand a standards-based interoperability layer, respectively. It supports training of text mining users and developers alike and demonstrates the merits of the approach through several use cases identified by scholars and experts from different scientific areas, ranging from generic scholarly communication to literaturerelated tolife sciences, food and agriculture, and social sciences and humanities. Through its infrastructural activities, OpenMinTeD’s vision is tomake operational a virtuous cycle in which a) primary content is accessed through standardised interfaces and access rules b) by well-documented and easily discoverable text mining services that process, analyse, and annotate text c) to identify patterns and extract new meaningful actionable knowledge, which will be used d) for structuring, indexing, and searching content and, in tandem, e) acting as new knowledge useful to draw new relations between content items and firing a new mining cycle. To achieve its goals, OpenMinTeD brings together different stakeholders, content providers and scientific communities, text mining and infrastructure builders, legal experts, data and computing centres, industrial players, and SMEs.

Breast cancer is the most common cancer among women with significant death rates and economic impact. In daily routine clinics, breast cancer is usually classified on the basis of three immunohistochemical markers (ER, PR and HER2). Triple-negative breast cancer (TNBC) is a subtype defined by the negativity of all these markers, which shows an adverse clinical course. It is characterized by a considerable gene expression heterogeneity that leads to a lack of availability of targeted therapies. Positive clinical trials relying on various forms of immunotherapy have shifted the paradigm of diverse malignancies from cytotoxics to novel immunomodulator drugs. The results in TNBC, however, are not as positive. In a recent taxonomic effort of the hosting group, TNBC has been re-classified on the basis of the activation status of six protein kinases, which in turn constituted novel targets for this disease. One of them, the 70-kDa ribosomal protein S6 kinase (P70S6K), which was associated with an adverse clinical outcome, showed negative correlation with tumor-infiltrating lymphocytes (TILs) abundance. The fact that P70S6K has been associated with immunosuppressive mechanisms and that there is a positive correlation between the number of TILs and the clinical outcomes in TNBC, suggests that the role of P70S6K may be related to pleiotropic and/or opposing properties of tumor progression. By using a combination of multiparametric flow cytometry, bulk/single-cell gene expression analysis and in vivo experiments in mouse models, this proposal aims to unravel the impact of P70S6K modulation over the already known relevant immune-oncology targets/axes as well as the therapeutic consequences of P70S6K blockade in TNBC. These studies will provide a better understanding of the lymphocyte-related responses modulated by P70S6K, with the potential to find new therapies for patients suffering from TNBC and possibly a broader range of malignances.