The endoplasmic reticulum (ER) can rapidly reorganize its functional domains and inter-organelle communication sites in response to cellular demands. ER-mitochondria communication is essential for normal cell physiology, as it conveys lipid exchange, mitochondrial calcium uptake, among other vital processes for mitochondrial function. In neurons, activity-mediated dynamics of ER and mitochondria are required for synaptic responsiveness to induction of synaptic plasticity and stimulating neuronal activity increases the number of ER-mitochondria contact sites (ERMCSs). Whilst system modelling predicts that ERMCSs control the postsynaptic energy landscape, the actual contribution of synaptic and perisynaptic inter-organelle dynamics to synaptic plasticity is still quite unknown. The small and compact structure of dendrites constrains the visualization of local ER-mitochondria contact site dynamics, being the application of nanoscopy techniques fundamental to follow these processes upon induction of synaptic plasticity. The use of cutting-edge super-resolution microscopy in this project will provide unprecedented spatiotemporal resolution to the study of activity-mediated ER and mitochondria dynamics and inter-organelle contacts heterogeneity in live neurons. Likewise, it will clarify the contribution of ERMCSs to sustain normal dendritic physiology as well as the intricate system triggering and upholding synaptic plasticity. Dysfunction of the ERMCSs has been reported in various neurodegenerative disorders due to mutation in proteins promoting and supporting ER-mitochondria communication. Neurodegenerative disorders are responsible for a great burden in disease, as dementias alone affect over 7 million people in Europe and this figure is expected to increase dramatically with aging of the population.

Modern society is evolving to a scenario in which all daily activities will be monitored using smart sensors. The provision of rapid, reliable and decentralized data is crucial and chemical sensors are current candidates for this purpose. VolThinSens puts forward an innovative sensing strategy from the ground up for reliable detection of ions addressing problems that constitute the bottleneck for the final application of electrochemical sensors in real contexts. To achieve this, the research methodology of VolThinSens involves the exploration of thin ion-sensing membranes based on new materials by using voltammetry and innovative techniques that the project will put forward for the study of the membrane robustness. The developed sensors will be interrogated using coulometry towards a calibration-free technology based on counting charges of the ion analyte that are implied in the electrochemical process. VolThinSens will provide a solution for these two challenges offering robust ion sensors with a wide application perspective within EU priorities such as “citizens’ welfare” and “protecting nature”, among others. The final demonstration of the concept is conceived as the integration of the developed voltammetric sensors for the detection of two ions with pharmacological/clinical and environmental relevance as proof-of-concept: lithium and ammonium. Thus, lithium will be detected in urine, serum and dissolution testing of pharmaceuticals and ammonium in aquatic systems. Interestingly, in situ sensing is aimed through the implementation of the ammonium sensor into a custom-built profiler ion analyser and its deployment in a lake for levels mapping in depth and time axis. VolThinSens will enhance EU excellence and competitiveness in pharmacological/clinical control as well as water issues through the provision of trustable relevant data.

Lung cancer has the highest incidence and mortality rates of all cancers, and patient survival is strongly linked to early detection. Therefore, low-dose CT screening of high-risk individuals, the only method proven to improve survival, is now recommended by major health organisations. There are, however, concerns with the high rate of false positives and increased radiation exposure associated with screening. We propose to investigate the clinical benefits of spectral CT for lung nodule detection and characterisation. The unique, photon-counting, spectral silicon detector developed by the host group offer twice the resolution, no lower dose limit, reduced artefacts, and higher contrast sensitivity than current state-of-the-art. Our hypothesis is that the patient dose can be significantly reduced in both the detection and characterisation steps, and that the higher resolution will reduce false positives. The reduction in screening dose alone would prevent an estimated 15 cases of induced cancer per 10,000 individuals screened. Fewer false positives would then further reduce the dose through fewer follow-ups and characterisations, lower clinical costs and workload, and reduce patient distress. The fellowship would allow the researcher to benefit from the world-class research, close ties to commercial partners and strong international collaborations of the host, and the exceptional clinical expertise of the partner organisation. In particular, training in cutting-edge detector technology, novel image reconstruction techniques and management of patient studies would complement the researcher’s strong background in medical physics and image analysis. The training, expected high-impact research and networking opportunities will strongly enhance the career prospects of the researcher, the outreach activities will give public awareness of the potential of spectral CT, and the expected clinical gain will benefit society at large, in particular future lung cancer patients.

From Landscapes to Earthscapes: Understanding Visual Cultures of Global Environmental Crisis and the Making of Global Environmental Images, 1945-present (EARTHSCAPES) EARTHSCAPES will contribute to current debates on the origins and possible futures of the environmental crisis by providing an innovative historical, social and political perspective on the production, circulation and reception of global environmental images since the beginning of the Cold War. It will further our understanding of the role of images in science by means of a thorough historical, political and sociological analysis of case studies, focusing on visualisations that allow for a global interpretation and understanding of our environment (hence the term “global environmental images”). The images concerned by this project help communicate global and a priori invisible environmental phenomena (global temperature, ozone levels, sea-level rise, climate change, etc.). By making the invisible visible, global environmental images reveal to be always both, the very tools that enable scientists to understand complex environmental and geophysical processes, and the instruments that allow them to share their findings with decision makers and the larger public. Images fulfil therefore always two functions; they are both: objects and instruments of knowledge. Yet few studies have explored in detail this double function, allowing to understand how global environmental processes are visually produced, represented, rendered evident, and consumed. Hence, a historically informed interdisciplinary study is urgently needed, also because the past may hold crucial answers for the future. EARTHSCAPES main aim is to close the research gap by analysing how iconic paintings, photographs, maps, graphs, visualisations and remote sensing images profoundly shaped environmental discourse, and a holistic and dynamic understanding of the Earth system since the beginning of the Cold War.

Membrane proteins constitute a third of the human proteome and their relevance to disease has led these proteins to make up more than half of all current drug targets. However, despite this push to identify agents for membrane proteins, the number of established disease-associated targets are limited. The 'open' and solvent-accessible nature of most membrane protein orthosteric sites often results in limited specificity of potential drugs. The Trans-Membrane domains (TMD) while displaying greater variability among membrane proteins were however long considered lacking in specific interactions. But significant developments in experimental techniques are now identifying this domain to interact and be actively regulated by the diverse lipid components of the membrane. This Lipopeutics project attempts to determine if the analysis of the protein's Lipid interactions can be a pathway to the development of allosteric drugs targeted at these bilayer-exposed pockets. Unfolding in three major steps, the project first aims to identify specific lipid binding sites with the TMD through the use of long-timescale coarse-grain Molecular Dynamics simulations. Subsequently, the role of this lipid binding event in the protein's functional modulation is validated through atomistic simulations using the Markov State Modelling approach. Finally, cheminformatic screening is used to design lipid-mimicking compounds that are capable of binding within the hydrophobic pocket and stabilizing specific protein functional states.