Refractory tumors and emergence of drug resistance are the most important challenges in cancer therapeutics. The non-cancerous determinants of therapeutic response and particularly the role of the tumor microenvironment (TME) in resistance are poorly understood. I previously described the crucial role of cancer-associated fibroblasts (CAFs) in key tumorigenic processes, including matrix remodeling, cancer cell invasion and growth. Importantly, these aggressive CAF phenotypes are controlled by mechanical reprogramming and mechanotransduction pathways. Within therapeutic resistance contexts, I hypothesize that preexistent and therapy-induced aberrant activation of mechanotransduction signaling in CAFs leads to the generation of refractory TMEs affecting cancer cell signaling and the behavior of accessory stromal cells such as endothelial and immune cells. As a result, tumors will present: (i) abnormal vasculature associated with reduced drug perfusion and chemotherapy efficacy; (ii) increased production of pro-survival signals affecting targeted therapy; and (iii) inactivation of cytolytic T cells and reduced responses to immunotherapy. I propose that CAF-based biomarkers will improve our capacity to identify patients most likely to respond to these therapeutics. In addition, targeting mechanotransduction in CAFs will significantly increase efficacy in non-responders. Focusing in colorectal cancer, I will use patient-derived CAFs as a tractable system and organ-on-chip, in vitro and preclinical models of CAF-mediated resistance, and combinatorial chemistry to systematically elucidate the molecular and biological features conferring CAFs their privileged therapy-resistance properties. This will illuminate novel and general mechanisms whereby TME characteristics influence tumorigenesis, and inform the development of refined biomarkers to stratify patients and next generation combinatorial therapies (including anti-CAF therapies) with reduced risk of recurrence.

Optical isolator, or optical diode, is a device, which allows the transmission of light in only one direction. They are used in fibre optic communication to prevent back reflections and improve signal-to-noise ratio. The development of on-chip optical communications requires downscaling of optical components, e.g replacing optical fibres with nanoscale waveguides. The miniaturization of optical isolators is therefore a key step towards integrated photonic circuits. We approach this challenge by taking advantage of surface plasmon resonances that can squeeze light down to nanoscale dimensions. We combine plasmonic waveguides with ferroelectric and -magnetic materials that, in turn, break the space-inversion and time reversal symmetries to create non-reciprocal conditions for light propagation. The ferroelectric and magnetic materials provide us with an additional interesting advantage: their optical properties can be adjusted by applying external electric and magnetic fields, enabling active control over light in nanoscale. The proposed research project brings together the candidate’s expertise in plasmonics and the hosting group’s established knowledge in oxide thin films. This creates excellent conditions for training through research and knowledge transfer. We envision two significant outcomes: (i) demonstration of a proof-of-concept plasmonic isolator based on symmetry considerations and (ii) assessing the viability of using active oxide materials as tools to control plasmon propagation with external fields. The H2020 Innovation Union initiative strives to drive economic growth in the EU by innovation. In line with this strategy, we recognize that EMPHASIS offers ample potential for technological applications and include strategies to ensure that the potential can be realized.

The offshore marine area of Cap de Creus (NW Mediterranean), characterised by its complex geological setting and rich epibenthic ecosystem, was declared a Site of Community Importance (SCI) of the Natura 2000 Network in 2014. Although environmental factors play a fundamental role in the distribution of benthic fauna, commercial fishing was found to exert a significant effect on the diversity and structure of benthic communities, especially on the soft-bottom areas of the shelf. The Marine Strategy Framework Directive (MSFD) determines that thematic strategies should be implemented to preserve its marine resources following an ecosystem-based approach, setting environmental targets and implementing a monitoring program to evaluate if conservation objectives are met. There is currently an array of imaging technologies at our disposal that could be used to monitor the benthic ecosystems of this SCI, but most would require highly elevated budgets to be operated on a regular basis. In this scenario, the project MONICA aims to explore the potential of recently developed low-cost imaging technologies (i.e., the Azor drift-cam) to explore and monitor the shelf and slope habitats of Cap de Creus to provide a cost-effective response to the demands of the MSFD. With this technology, MONICA will identify changes in the composition and structure of benthic communities since the creation of the SCI and generate a new baseline for the implementation of a correct monitoring program. Furthermore, it will employ low-cost Baited Remote Underwater Videos (BRUVs) to characterise the demersal fish assemblages and determine the functional role of benthic communities. If successful, these technologies could open the doors to generate essential data at a significantly lower cost in other areas of the Mediterranean to assist in decision-making processes and policy development for the conservation and restoration of marine biodiversity in times of rapid changes.

Solid catalysts are key components of many industrial processes, offering advantages such as reuse and ease recovery. This research programme aims to develop a new concept and methodology for the synthesis of zeolite catalysts. Zeolites are solid, porous catalysts that have wide ranging industrial applications for gas adsorption, separation and catalysis. While a relatively large number of zeolites have been synthesised, zeolite selection as catalyst for a particular reaction still retains a large element of trial and error. Our objective is to design a zeolite synthesis methodology that creates pores and cavities in the resulting zeolite that approach a “molecular recognition” pattern to catalyze the desired reaction. The approach focuses on the study of the reactions transition states since it is accepted that the most efficient catalysts are those that lower the transition state energy in the reaction, boosting the catalytic activity and efficiency. We will study the transition state of the desired reaction and design and synthesise transition state mimics to be used as Organic Structure Directing Agents for the synthesis of zeolites. By maximizing the host-guest interactions between zeolite and transition state, the efficiency of the catalyst will be increased. We aim to obtain tailor made catalysts for a chosen spectrum of reactions that also have clear industrial applications. Synthesis of highly efficient catalysts for particular industrially relevant applications will lead to lower energy consumption, fewer by-products and lower consumption of reactants. In summary, this will result in more sustainable processes. In many industrial applications a 1% increase in selectivity can represent more than 3000Tm/year additional manufacturing in a single unit.