This project undertakes the first comprehensive investigation of early modern ecology. NEWWORLD counters the standard historiographical argument that ecological concern is a recent phenomenon. A key element in that claim is the assumption that the terminology of environmental care is recent: the term 'ecology' was invented in the 19th century by Ernst Haeckel; 'sustainability' is a 20th-century coinage; 'the environment' was used for the first time in English by Thomas Carlyle in 1827. Yet, these terms that now help to define ecological sensibilities arose from long-lasting debates. The leading claim of this project is that early modernity was a particularly fertile period for ecological reflection. NEWWORLD proposes an innovative methodology to capture the breadth and philosophical substance of early modern ecological debates: it proceeds from present-day terms to construct terminological and conceptual constellations in early modern texts. It uses a technique that historians (of philosophy) label 'controlled anachronism', and which this project aims to fully exploit for the first time on a large scale. The objectives, subdivided into the four main areas 'Environment', 'Pollution', 'Sustainability', and 'Ecological Justice', involve tracing a symbiotic connection between metaphysical, natural-philosophical, religious, and ethical ideas. NEWWORLD will both reveal the specificities of early modern thought on ecological matters, and pioneer a dialogue with ecological debates as we know them today. The project's main output will be a multi-volume philosophical history of environmental care in the early modern period. This will be complemented by the curation of an exhibition, featuring 3D models of cosmographical images and projections of early modern plans for ideal cities, showing them to be laboratories of ecological views. NEWWORLD seeks to offer a new paradigm for the intervention of the history of philosophy in present-day debates on ecology, and beyond.

Colorectal cancer (CRC) results from the accumulation of genetic and epigenetic changes in colonic epithelial cells. Epigenome studies revealed that virtually all CRCs contain aberrantly methylated genes and perturbed methylation patterns. Ten-Eleven Translocation (TET) protein family dioxygenases oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and further to other oxidized 5mCs, supporting active DNA demethylation and helping maintain epigenomic stability. Loss of TET1 is an oncogenic driver in some CRCs. My preliminary analysis indicates that human CRCs have low TET2 mRNA levels compared to normal colorectal tissue, and suggests that low TET2 expression predicts increased mutational load and reduced overall survival. However, whether TET2 deficiency contributes to CRC pathogenesis, or represents a bystander event, remains to be established. In this proposal, I will elucidate the role of TET2 in CRC pathogenesis by testing whether TET2 knockdown induces methylome and transcriptome reprogramming, ultimately promoting (epi)genomic instability and tumor growth. I will also investigate correlations between TET2 defects and molecular/clinico-pathological parameters, and probe TET2 expression as predictive biomarker of response to CRC therapies. With these aims, I will use a multi-disciplinary approach, combining cell biology, cancer epigenetics, bioinformatics, human and mouse studies with cutting-edge techniques such as 3D cell culture and RNA-seq. This study should establish a clear causal link between TET2 loss and CRC pathogenesis, providing new insight into the mechanism of TET2-mediated tumor suppression and leading to the development of innovative therapies that exploit vulnerabilities of TET2-deficient CRC cells. Overall, this project has both basic and translational significance, and the potential to advance our understanding of CRC carcinogenesis and therapeutic response.

Engineering new solutions for powering smart portable devices is key to sustain billion-scale connected objects and to provide a greener alternative to batteries. Indoor Photovoltaics (PVs) - with a projected market of $850 million by 2023 - relying on conversion of visible indoor light- can sustain this challenge, capitalizing on the development of flexible, semi-transparent, colored and easily integrated energy generation devices. Despite the urgency and the large market potential, current PV technologies mostly fail, leveraging on rigid and bulky systems fabricated by energy-intensive processes (i.e. Silicon PVs) or on carbon-based technologies not yet in the market for their insufficient durability. Hybrid perovskites with wide band gap (2eV), with their easy tunability, structural flexibility, and lightweight, hold the potential for a transformative solution in visible PVs. However, lower efficiency compared to low-band gap ones, reliance on toxic elements and insufficient stability hamper their scaling up. ELOW-DI faces this challenge by engineering the perovskite dimensionality as the key variable to unlock device instability while allowing for efficient visible light conversion. This will be obtained i) by developing intrinsically stable low-dimensional perovskites (LDPs) leveraging on non-toxic elements and stable hydrophobic units and 2) by controlling material nucleation and consequent thin film morphology to obtain vertically oriented crystalline nanopillars, essential to ensure efficient charge extraction in the device while reducing unwanted recombination. Upon the demonstration of the proof of concept on lab-scale, research will be moved to a completely new direction by engineering large area devices while ensuring the scalability of the nanoscale material properties. ELOW-DI is timely, and it will generate the new multidisciplinary knowledge from material to device engineering- which is now needed for the next-gen of indoor PV solutions.

Cancer is a global health burden. In-vitro pre-clinical models play a key role in fighting this burden by encompassing all the activities prior to clinical trials, from tumor microenvironment reconstruction to drug candidate selection. However, the frequent failure of promising pre-clinical drug candidates highlights two major drawbacks of these models: (i) the difficult reproduction of the dynamic cancer structure related to numerous physical cues; (ii) their experimental nature that suffers from high costs, long times, and limited understanding. Consequently, the relationship between dynamic physical cues, cell behavior, and drug efficacy is still unknown. CoDe4Bio tackles such a huge knowledge deficiency. We propose a radical methodology shift to a computational approach to harness programmable materials, able to change properties on demand, and realize dynamic 4D biofabricated models whose stimuli-triggered evolution over time (4th dimension) induces targeted physical cues on cancer cells. We will leverage my extensive experience with smart materials and structures to address the challenges of this multidisciplinary project. Specifically, we will develop a computational design framework for 4D biofabrication that combines new data-, geometry-, and model-based methods with additive manufacturing and in-vitro observations. This framework will allow us to develop customized stimuli-responsive materials and engineer a new generation of 4D constructs with programmable mechano-structural properties and acting as mechanical regulators. We will assess the constructs in-vitro on chronic lymphocytic leukemia to achieve a deep understanding on how complex physical cues within lymph nodes and bone marrow affect this incurable cancer in relation to chemoimmuno and targeted therapies. CoDe4Bio will push the frontiers of solid and computational mechanics to unveil unconventional routes for pre-clinical drug screening and lay the foundation for effective dynamic cancer models.

Subduction of one tectonic plate below another is the primary cause of catastrophic geological events such as earthquakes and explosive volcanism that directly impact thousands of kilometers of coastal and mountain areas located on convergent margins. Real-time geophysical or seismic data only provide static snapshots of these subduction zones today. Therefore, quantitative understanding of the rates and true depths of subduction can only be achieved by determining the pressure-temperature-time-depth histories of Ultra-High-Pressure Metamorphic (UHPM) rocks that have been subducted to pressures greater than 3 GPa and subsequently exhumed. Conventional mineral thermo-barometry is severely challenged in UHPM terraines and thus the mechanisms attending the downwards transport of crustal material, and its return back to the Earth’s surface (exhumation), are still a matter of vigorous debate. The TRUE DEPTHS project will develop X-ray diffraction analysis of the anisotropic elastic interactions of inclusion minerals trapped inside host minerals. I will develop non-linear elasticity theory to provide a method that will be uniquely able to determine whether significant deviatoric stresses are recorded by UHPM rocks. By applying this method to samples from carefully selected field areas, I will be able to determine if metamorphic phase equilibria represent the true depths of UHPM, in which case subduction to depths in excess of 90 km must occur. Alternatively, quantitative measurements of large deviatoric stresses could indicate that tectonic over-pressure can account for the observed phase equilibria, thus not requiring deep subduction. If overpressurized domains are present in tectonically thickened lithosphere, they may represent a driving force for stress release leading to earthquakes. The results will provide new constraints on earthquake triggering mechanisms and how the styles of subduction and its detailed mechanisms have evolved over Earth’s history.