Our planet is changing at a pace never experienced before. Ecosystems worldwide are impacted by multiple anthropogenic pressures and are experiencing abrupt changes, sometimes leading to regime shifts. Marine ecosystems are prone to these dynamics and regime shifts are at the spotlight of research which seeks to reduce the uncertainties related to our incomplete understanding of these processes. Three main questions need to be answered to understand regime shifts: when they happen; i.e. detection, why; i.e. drivers and characteristics, and how; i.e. mechanisms. Present literature has focused mainly on detecting regime shifts, neglecting feedbacks and how ecosystems function. This ignorance has limited the causal understanding of these phenomena and has hindered the capacity to predict them, a fundamental step under global changes. FEEDRES brings feedbacks mechanisms at the fore and aims at responding to all the three challenges to understand and project regime shifts. To fulfil this, FEEDRES will develop a cutting-edge methodological framework combining methods from system dynamics theory and ecology. FEEDRES will follow three steps. 1) Map worldwide marine regime shifts – Through a systematic mapping FEEDRES will assess the extent of regime shifts, highlighting knowledge gaps (when). 2) Empirically study the important structural elements and connections that characterize marine systems under regime shifts (from populations to socio-ecological systems) – FEEDRES will apply a two-step modelling approach to understand how the system change during regime shifts (why). 3) Develop mechanistic models to understand how changes in feedback mechanisms mediate marine regime shifts (how). Based on the knowledge developed FEEDRES will identify common feedback types in marine systems and will project the likelihood of regime shifts. FEEDRES will revolutionise ecosystem science and will increase the understanding on how complex systems behave under cumulative stressors.

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and the main monogenetic cause of autism spectrum disorder. FXS is caused by the epigenetic inactivation of the FMR1 gene during the first trimester of gestation. FMR1 encodes for the fragile X mental retardation protein (FMRP), which regulates the transport and translation of mRNAs involved in brain development. Already at 6 months of age, FXS infants display structural alterations in several brain areas, including the fronto-striatal circuit, suggesting an altered neural network assembly during fetal brain development. Structural anomalies in the fronto-striatal circuit may underlie symptoms that strongly impair the life of FXS patients, such as attention deficit, hyperactivity, stereotypic language and motor behavior, and problems with impulse control. This project aims at understanding the causal factors of the altered assembly of the fronto-striatal circuit in FXS fetuses. To achieve this goal, we will generate human cortical and striatal brain organoids from FXS naïve induced pluripotent stem cells, and assemble these organoids into cortico-striatal assembloids. The resulting in vitro model will be used to conduct research in two directions. First, it will allow us to recapitulate cortico-striatal circuit assembly in FXS, identifying potential defects in axon growth and guidance, neuron morphology and neural connections. Second, we will investigate the molecular causes of these defects, in particular how the absence of FMRP affects the expression of proteins involved in the assembly of the FXS cortico-striatal circuit. These studies will make it possible, for the first time, to spatiotemporally follow the pathological events that cause FXS, both at the cellular and at the molecular level, and they will pave the way for the identification of new therapeutic strategies to prevent the development of the disease.

Organic synthesis is still one of the main limiting factors in drug-discovery projects. Traditionally, the generation of compounds libraries requires tedious synthetic routes to introduce modifications into the lead compound, thus the implementation of new methodologies to modify drugs in a selective way in the late stages of their synthesis is highly attractive. In SupraPhoCat project, several supramolecular receptors will be provided with catalytic activity and combined with photoredox catalysis to achieve unprecedent asymmetric C-H funtionalization reactions with exquisite selectivity, using CO2 as non-toxic abundant C1 building block. This ambitious project will establish new methodologies for C-H Late-Stage Functionalization of drugs, which is a key point towards the development of libraries of compounds according to EU green chemistry insights. This Marie Sklodowska Curie action will merge the expertise of the host group (Prof. Luca Dell’Amico, NanoMolCat group from University of Padova) in CO2 valorisation methods and photoredox catalysis with the expertise of the fellow on supramolecular chemistry, molecular recognition and organocatalysis. Also, this project has been designed to augment and complement the research and transferable skills sets of the fellow and will greatly enhance his career prospects to become a mature and independent scientist. Through the training and the research results arising, the fellowship will be beneficial to the candidate, the host institution and European scientific and social environment. This research will allow a great improvement of the state-of-the-art in the construction of active organic molecules through a new, powerful, and impacting synthetic methodology, raising the standing of EU chemistry within this field at a global level. Hence, SupraPhoCat will constitute a significant contribution to the field, and will suppose a benefit for synthetic organic chemists, pharma-, agro- and fine-chemicals industries in EU.