The project TREM2MICROENGINES aims at demonstrating that raising and restoring TREM2 expression in the brain of Alzheimer’s disease (AD) and Nasu–Hakola disease (NHD) patients, and in particular in their microglia, would result in therapeutic benefit. AD is a severe neurodegenerative disorder that represents the most frequent form of dementia among the elderly which affects approximately 5.1 million Americans and this number is supposedly tripled by 2050. AD is believed to result from the deposition of extracellular amyloid-β (Aβ)-containing plaques. TREM2-Triggering receptor expressed on myeloid cells 2 is a microglia cell-surface receptor whose deficiency or haplo-insufficiency augments Aβ accumulation due to a dysfunctional response of cells, which become apoptotic. Homozygous, loss-of-function mutations in TREM2 also cause the autosomal recessive disorder NHD, a ultra-rare inherited disease of the white matter (WM) with typical onset in the adult age, and patho-physiologically characterized by microglial dysfunction (microgliopathy). The key clinical feature of NHD is progressive presenile dementia usually leading to death in the fifth decade of life NHD patients also lack curative treatments. A relevant proportion of AD cases and all forms of NHD are caused by pathogenic mutations in the Trem2 gene which lead to microglia dysfunction contributing to and/or causing the onset and manifestations of AD and NHD. Based on this provision, our working hypothesis is that transplantation of HSCs engineered by LVs to express robust TREM2 levels in response to tissue damage in CNS-engrafted myeloid/microglia cells would modulate neuroinflammation, restore physiological microglia functions and contribute preventing and reducing Aβ accumulation in the CNS of AD and NHD patients. No existing approaches currently allow targeting microglia dysfunction in AD or in NHD, nor at enhancing microglia specific function through a microglia-targeted TREM2 delivery/engineering.
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.
The research will identify and raise awareness about the audiovisual conventions and communication tactics of animation in multimedia science outreach, in respect to the representation of invisible objects (too big, too small, too far away in space and time). The research is in the field of animated documentary, a major point in the Animation Studies agenda (Honess Roe, 2013). It is also based on the epistemology of scientific communication; as Daston and Galison argued (2007), «truth-to-nature» objectivity is being superseded by visuals balancing art and science. Merleau-Ponty (1964) had previously called for an equilibrium between objectivity and subjectivity in science outreach, due to the new “invisible” frontiers of knowledge. The action will start with 12 months at the Lucerne University of Applied Sciences and Arts, whose excellence in visual research and its interdisciplinary environment will support the Researcher in: 1) building a list of animations in multimedia science outreach from 1980; 2) critically engaging the conventions and tactics from the point of view of animation theory, 3) of animators and 4) of scientists (in dialogue with the resident experts on data visualization). The next 12 months will be hosted by the Department of Cultural Heritage of the University of Padova, Italy. With the collaboration of the Department of Information Engineering and the CICAP (the Italian committee for scientific skepticism), the results from the outgoing phase will be used to: a) create an open access database of multimedia science outreach about the “invisible”; b) set up educational actions; c) create a permanent committee to promote good practices in animation for science. The Researcher will take advantage of his expertise in animation history and theory, his contacts with the industry and with animation schools, and his teaching experience. The research will consolidate his career and make him a mediator between academia, scientists, and filmmakers.